531 results
Search Results
2. Frequency-specific sensitivity of 3T3-L1 preadipocytes to low-intensity vibratory stimulus during adipogenesis.
- Author
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Baskan O, Sarigil O, Mese G, and Ozcivici E
- Subjects
- 3T3-L1 Cells, Animals, Bone Marrow Cells, Cell Differentiation, Mice, Osteogenesis, Adipocytes, Adipogenesis genetics
- Abstract
Adipocyte accumulation in the bone marrow is a severe complication leading to bone defects and reduced regenerative capacity. Application of external mechanical signals to bone marrow cellular niche is a non-invasive and non-pharmaceutical methodology to improve osteogenesis and suppress adipogenesis. However, in the literature, the specific parameters related to the nature of low-intensity vibratory (LIV) signals appear to be arbitrarily selected for amplitude, bouts, and applied frequency. In this study, we performed a LIV frequency sweep ranging from 30 to 120 Hz with increments of 15 Hz applied onto preadipocytes during adipogenesis for 10 d. We addressed the effect of LIV with different frequencies on single-cell density, adipogenic gene expression, lipid morphology, and triglycerides content. Results showed that LIV signals with 75-Hz frequency had the most significant suppressive effect during adipogenesis. Our results support the premise that mechanical-based interventions for suppressing adipogenesis may benefit from optimizing input parameters., (© 2022. The Society for In Vitro Biology.)
- Published
- 2022
- Full Text
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3. Engineering and Characterization of a Biomimetic Microchip for Differentiating Mouse Adipocytes in a 3D Microenvironment.
- Author
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Chen YT, Ramalingam L, Garcia CR, Ding Z, Wu J, Moustaid-Moussa N, and Li W
- Subjects
- 3T3-L1 Cells, Adipocytes, White drug effects, Adipocytes, White metabolism, Animals, Cell Proliferation, Cyclooxygenase 2 genetics, Cyclooxygenase 2 metabolism, Cytokines genetics, Cytokines metabolism, Female, Glucose Transporter Type 4 metabolism, Inflammation Mediators metabolism, Lipopolysaccharides pharmacology, Mice, Mice, Inbred C57BL, Adipocytes, White physiology, Adipogenesis, Biomimetic Materials, Cell Culture Techniques, Three Dimensional instrumentation, Lab-On-A-Chip Devices, Microfluidic Analytical Techniques instrumentation
- Abstract
Although two-dimensional (2D) cell cultures are the standard in cell research, one pivotal disadvantage is the lack of cell-cell and cell-extracellular matrix (ECM) signaling in the culture milieu. However, such signals occur in three-dimensional (3D) in vivo environments and are essential for cell differentiation, proliferation, and a range of cellular functions. In this study, we developed a microfluidic device to proliferate and differentiate functional adipose tissue and adipocytes by utilizing 3D cell culture technology. This device was used to generate a tissue-specific 3D microenvironment to differentiate 3T3-L1 preadipocytes into either visceral white adipocytes using visceral adipose tissue (VAT) or subcutaneous white adipose tissue (SAT). The microchip has been tested and validated by functional assessments including cell morphology, inflammatory response to a lipopolysaccharide (LPS) challenge, GLUT4 tracking, and gene expression analyses. The biomimetic microfluidic chip is expected to mimic functional adipose tissues that can replace 2D cell cultures and allow for more accurate analysis of adipose tissue physiology., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
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4. The long-chain polyfluorinated alkyl substance perfluorohexane sulfonate (PFHxS) promotes bone marrow adipogenesis.
- Author
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Garmo LC, Herroon MK, Mecca S, Wilson A, Allen DR, Agarwal M, Kim S, Petriello MC, and Podgorski I
- Subjects
- Animals, Mice, Male, Signal Transduction drug effects, Bone Marrow Cells drug effects, Bone Marrow Cells pathology, Adipose Tissue drug effects, Adipose Tissue metabolism, Adipogenesis drug effects, Fluorocarbons toxicity, Bone Marrow drug effects, Bone Marrow metabolism, PPAR gamma metabolism, Mice, Inbred C57BL, Sulfonic Acids toxicity
- Abstract
Per- and polyfluoroalkyl substances (PFAS) bioaccumulate in different organ systems, including bone. While existing research highlights the adverse impact of PFAS on bone density, a critical gap remains in understanding the specific effects on the bone marrow microenvironment, especially the bone marrow adipose tissue (BMAT). Changes in BMAT have been linked to various health consequences, such as the development of osteoporosis and the progression of metastatic tumors in bone. Studies presented herein demonstrate that exposure to a mixture of five environmentally relevant PFAS compounds promotes marrow adipogenesis in vitro and in vivo. We show that among the components of the mixture, PFHxS, an alternative to PFOS, has the highest propensity to accumulate in bone and effectively promote marrow adipogenesis. Utilizing RNAseq approaches, we identified the peroxisome proliferator-activated receptor (PPAR) signaling as a top pathway modulated by PFHxS exposure. Furthermore, we provide results suggesting the activation and involvement of PPAR-gamma (PPARγ) in PFHxS-mediated bone marrow adipogenesis, especially in combination with high-fat diet. In conclusion, our findings demonstrate the potential impact of elevated PFHxS levels, particularly in occupational settings, on bone health, and specifically bone marrow adiposity. This study contributes new insights into the health risks of PFHxS exposure, urging further research on the relationship between environmental factors, diet, and adipose tissue dynamics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
5. Caveolin-2 controls preadipocyte survival in the mitotic clonal expansion for adipogenesis.
- Author
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Choi M, Jeong K, and Pak Y
- Subjects
- Animals, Mice, Cell Survival genetics, Cyclin B1 metabolism, Cyclin B1 genetics, 3T3-L1 Cells, Apoptosis genetics, Adipogenesis genetics, Mitosis genetics, Adipocytes metabolism, Adipocytes cytology, CDC2 Protein Kinase metabolism, CDC2 Protein Kinase genetics, Cyclin-Dependent Kinase Inhibitor p21 genetics, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Caveolin 2 genetics, Caveolin 2 metabolism
- Abstract
Here, we report that Caveolin-2 (Cav-2) is a cell cycle regulator in the mitotic clonal expansion (MCE) for adipogenesis. For the G2/M phase transition and re-entry into the G1 phase, dephosphorylated Cav-2 by protein tyrosine phosphatase 1B (PTP1B) controlled epigenetic activation of Ccnb1, Cdk1, and p21 in a lamin A/C-dependent manner, thereby ensuring the survival of preadipocytes. Cav-2, associated with lamin A/C, recruited the repressed promoters of Ccnb1 and Cdk1 for activation, and disengaged the active promoter of p21 from lamin A/C for inactivation through histone H3 modifications at the nuclear periphery. Cav-2 deficiency abrogated the histone H3 modifications and impeded the transactivation of Ccnb1, Cdk1, and p21, leading to a delay in mitotic entry, retardation of re-entry into G1 phase, and the apoptotic cell death of preadipocytes. Re-expression of Cav-2 restored the G2/M phase transition and G1 phase re-entry, preadipocyte survival, and adipogenesis in Cav-2-deficient preadipocytes. Our study uncovers a novel mechanism by which cell cycle transition and apoptotic cell death are controlled for adipocyte hyperplasia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
6. Cleavage and polyadenylation factors are potential regulators of adipogenesis.
- Author
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Mostafa SM and Moore C
- Subjects
- Animals, Mice, Polyadenylation, RNA, Messenger genetics, RNA, Messenger metabolism, Adipocytes metabolism, Cleavage And Polyadenylation Specificity Factor metabolism, Cleavage And Polyadenylation Specificity Factor genetics, 3T3-L1 Cells, Adipogenesis genetics, Cell Differentiation
- Abstract
Objective: Alternative polyadenylation (APA) is a co-transcriptional process that leads to isoform diversity in the 3' ends of mRNAs. APA is known to occur during differentiation, and its dysregulation is observed in diseases like cancer and autoimmune disorders. It has been previously reported that differentiation of 3T3-L1 cells to adipocytes leads to an overall lengthening of mRNAs, but the proteins involved in this regulation have not been identified. The expression levels of subunits of the cleavage and polyadenylation (C/P) complex can regulate the choice of poly(A) site, which in turn can affect different cellular activities. In this paper, we studied the change in levels of C/P proteins during 3T3-L1 differentiation., Results: We observed that while the RNA expression of these proteins is unchanged during differentiation, the protein levels of some subunits do change, including a decrease in levels of CPSF73, the nuclease that cuts at the poly(A) site. However, overexpression of CPSF73 alone does not affect the efficiency and rate of differentiation., (© 2024. The Author(s).)
- Published
- 2024
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7. SERPINE1AS2 regulates intramuscular adipogenesis by inhibiting PAI1 protein expression.
- Author
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Zhang D, Ma X, Li H, Li X, Wang J, and Zan L
- Subjects
- Animals, Cattle, Gene Expression Regulation, Cell Differentiation genetics, Cell Proliferation genetics, Signal Transduction, Adipose Tissue metabolism, Adipose Tissue cytology, Adipogenesis genetics, Plasminogen Activator Inhibitor 1 genetics, Plasminogen Activator Inhibitor 1 metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Adipocytes metabolism, Adipocytes cytology
- Abstract
Antisense long non-coding RNAs (lncRNAs) played a crucial role in the precise regulation of essential biological processes and were abundantly present in animals. Many of these antisense lncRNAs have been identified as key roles in adipose tissue accumulation in livestock, underscoring their vital role in the regulation of animal physiology. Nonetheless, the functional roles of these antisense lncRNAs in regulating adipogenesis and the specific molecular mechanisms these processes were still unclear, which was a significant gap in current scientific research. In this study, we identified and characterized SERPINE1AS2, a novel natural antisense lncRNA, was highly expressed in the fat tissues of adult cattle and calves. Its expression gradually increased during the differentiation of intramuscular adipocytes. Through functional studies, we observed that knockdown of SERPINE1AS2 inhibited the proliferation and adipogenesis of intramuscular adipocytes, while overexpression of SERPINE1AS2 produced the opposite effect. RNA sequencing (RNA-seq) analysis following SERPINE1AS2 knockdown revealed that differential expression genes (DEGs) were significantly enriched in key signaling pathways, notably the MAPK, Wnt, and mTOR signaling pathways. Furthermore, SERPINE1AS2 interacted with Plasminogen Activator Inhibitor-1 (PAI1), forming RNA dimers through complementary base pairing and consequently influencing PAI1 expression. Interestingly, studies on PAI1 suggested that reduced expression facilitated adipogenesis and the downregulation of PAI1 alleviated the inhibitory effect of reduced SERPINE1AS2 on adipogenesis. In summary, this study suggested that SERPINE1AS2 played a crucial role in the adipogenesis of bovine intramuscular adipocytes by modulating the expression of PAI1. SERPINE1AS2 also regulated adipogenesis by engaging in the MAPK, Wnt, and mTOR signaling pathways. Our results suggested that SERPINE1AS2 had a complex regulatory mechanism on adipogenesis in intramuscular adipocytes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Linsen Zan reports financial support was provided by Ministry of Agriculture and Rural Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
8. Lipidomics and single-cell RNA sequencing reveal lipid and cell dynamics of porcine glycerol-injured skeletal muscle regeneration model.
- Author
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Sun Y, Xu Z, You W, Zhou Y, Nong Q, Chen W, and Shan T
- Subjects
- Animals, Swine, Single-Cell Analysis methods, Sequence Analysis, RNA methods, Signal Transduction, Transforming Growth Factor beta metabolism, Disease Models, Animal, Cell Differentiation, Lipid Metabolism drug effects, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Regeneration, Glycerol metabolism, Adipogenesis drug effects, Lipidomics methods
- Abstract
Aims: Intramuscular fat (IMF) infiltration and extracellular matrix (ECM) deposition are characteristic features of muscle dysfunction, such as muscular dystrophy and severe muscle injuries. However, the underlying mechanisms of cellular origin, adipocyte formation and fibrosis in skeletal muscle are still unclear., Main Methods: Pigs were injected with 50 % glycerol (GLY) to induce skeletal muscle injury and regeneration. The acyl chain composition was analyzed by lipidomics, and the cell atlas and molecular signatures were revealed via single-cell RNA sequencing (scRNA-seq). Adipogenesis analysis was performed on fibroblast/fibro-adipogenic progenitors (FAPs) isolated from pigs., Key Findings: The porcine GLY-injured skeletal muscle regeneration model was characterized by IMF infiltration and ECM deposition. Skeletal muscle stem cells (MuSCs) and FAP clusters were analyzed to explore the potential mechanisms of adipogenesis and fibrosis, and it was found that the TGF-β signaling pathway might be a key switch that regulates differentiation. Consistently, activation of the TGF-β signaling pathway increased SMAD2/3 phosphorylation and inhibited adipogenesis in FAPs, while inhibition of the TGF-β signaling pathway increased the expression of PPARγ and promoted adipogenesis., Significance: GLY-induced muscle injury and regeneration provides comprehensive insights for the development of therapies for human skeletal muscle dysfunction and fatty infiltration-related diseases in which the TGF-β/SMAD signaling pathway might play a primary regulatory role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships. that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
9. The obesogen bisphenol A promotes adipogenesis in canine adipose-derived stem cells: Potential implication in dog obesity.
- Author
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Park EJ, Lee S, Kim JY, Choi J, Lee YS, Park M, Jeon JH, and Lee HJ
- Subjects
- Animals, Dogs, Adipose Tissue metabolism, Cell Differentiation drug effects, Benzhydryl Compounds toxicity, Phenols toxicity, Adipogenesis drug effects, Obesity metabolism, Endocrine Disruptors toxicity, Stem Cells drug effects
- Abstract
The growing number of companion dogs has contributed to a rapidly growing market for pet products, including dog toys. However, little is known about the hazardous substances released from dog toys. This study aims to examine the potential presence of obesogens, a subset of endocrine-disrupting chemicals (EDCs) that are widely utilized as raw materials in the manufacture of dog toy components, and their effects on dog health. To achieve this, we adapted and employed a migration method typically used for children's products to simulate obesogen exposure in dogs through sucking or chewing toys. We demonstrated that out of various obesogens, bisphenol A (BPA) was released from dog toys into synthetic saliva, whereas phthalates and azo dyes were not detected in any of the leachates. Additionally, we found that BPA induced adipogenic differentiation in canine adipose-derived stem cells (cADSCs). Our RNA sequencing experiments revealed that BPA alters the adipogenesis-related gene signature in cADSCs by elevating the expression levels of ADIPOQ, PLIN1, PCK1, CIDEC, and FABP4. The associated transcriptional changes are involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which may contribute to the promotion of adipogenesis by BPA. Our findings suggest that companion dogs are at risk of BPA exposure, which may contribute to obesity in dogs. Therefore, the implementation of precautionary measures is crucial., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
10. GSK3 regulation Wnt/β-catenin signaling affects adipogenesis in bovine skeletal muscle fibro/adipogenic progenitors.
- Author
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Zhang J, Wang E, Li Q, Peng Y, Jin H, Naseem S, Sun B, Park S, Choi S, and Li X
- Subjects
- Animals, Cattle, beta Catenin metabolism, beta Catenin genetics, Cell Differentiation, Stem Cells metabolism, Stem Cells cytology, Adipogenesis, Glycogen Synthase Kinase 3 metabolism, Muscle, Skeletal metabolism, Muscle, Skeletal cytology, Wnt Signaling Pathway
- Abstract
Clarifying the cellular origin and regulatory mechanisms of intramuscular fat (IMF) deposition is crucial for improving beef quality. Here, we used single-nucleus RNA sequencing to analyze the structure and heterogeneity of skeletal muscle cell populations in different developmental stages of Yanbian cattle and identified eight cell types in two developmental stages of calves and adults. Among them, fibro/adipogenic progenitors (FAPs) expressing CD29 (ITGA7)
pos and CD56 (NCAM1)neg surface markers were committed to IMF deposition in beef cattle and expressed major Wnt ligands and receptors. LY2090314/XAV-939 was used to activate/inhibit Wnt/β-catenin signal. The results showed that the blockade of Glycogen Synthase Kinase 3 (GSK3) by LY2090314 promoted the stabilization of β-catenin and reduced the expression of genes related adipogenic differentiation (e.g., PPARγ and C/EBPα) in bovine FAPs, confirming the anti-adipogenic effect of GSK3. XAV-939 inhibition of the Wnt/β-catenin pathway promoted the lipid accumulation capacity of FAPs. Furthermore, we found that blocking GSK3 enhanced the paracrine effects of FAPs-MuSCs and increased myotube formation in muscle satellite cells (MuSCs). Overall, our results outline a single-cell atlas of skeletal muscle development in Yanbian cattle, revealed the role of Wnt/GSK3/β-catenin signaling in FAPs adipogenesis, and provide a theoretical basis for further regulation of bovine IMF deposition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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11. S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction
- Author
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Chakrabarty, Sagarika, Bui, Quyen, Badeanlou, Leylla, Hester, Kelly, Chun, Jerold, Ruf, Wolfram, Ciaraldi, Theodore P, and Samad, Fahumiya
- Subjects
obesity ,Histology ,Physiology ,Diet, High-Fat ,sphingosine 1 phosphate ,Diseases of the endocrine glands. Clinical endocrinology ,adipogenesis ,Mice ,Sphingosine ,Animals ,Humans ,t2d ,QP1-981 ,Sphingosine-1-Phosphate Receptors ,Biological Phenomena ,Inflammation ,hepatic inflammation ,QH573-671 ,hepatic steatosis ,Cell Biology ,RC648-665 ,adipose inflammation ,Fatty Liver ,Mice, Inbred C57BL ,s1pr3 ,lipids (amino acids, peptides, and proteins) ,Lysophospholipids ,Cytology ,Research Article ,Research Paper - Abstract
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to biological processes including cell growth, immune cell trafficking, and inflammation.We demonstrate that in Type 2 diabetic (T2D) subjects, plasma S1P levels significantly increased in response to the anti-diabetic drug, rosiglitazone, and, S1P levels correlated positively with measures of improved glucose homeostasis. In HFD-induced obese C57BL/6 J mice S1PR3 gene expression was increased in adipose tissues (AT) and liver compared with low fat diet (LFD)-fed counterparts. On a HFD, weight gain was similar in both S1PR3-/- mice and WT littermates; however, HFD-fed S1PR3-/- mice exhibited a phenotype of partial lipodystrophy, exacerbated insulin resistance and glucose intolerance. This worsened metabolic phenotype of HFD-fed S1PR3-/- mice was mechanistically linked with increased adipose inflammation, adipose macrophage and T-cell accumulation, hepatic inflammation and hepatic steatosis. In 3T3-L1 preadipocytes S1P increased adipogenesis and S1P-S1PR3 signalling regulated the expression of PPARγ, suggesting a novel role for this signalling pathway in the adipogenic program. These results reveal an anti-diabetic role for S1P, and, that S1P-S1PR3 signalling in the adipose and liver defends against excessive inflammation and steatosis to maintain metabolic homeostasis at key regulatory pathways.
- Published
- 2022
12. Regulatory network of metformin on adipogenesis determined by combining high-throughput sequencing and GEO database
- Author
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Zhicong, Zhao, Chenxi, Wang, Jue, Jia, Zhaoxiang, Wang, Lian, Li, Xia, Deng, Zhensheng, Cai, Ling, Yang, Dong, Wang, Suxian, Ma, Li, Zhao, Zhigang, Tu, and Guoyue, Yuan
- Subjects
gene expression omnibus ,Adipogenesis ,Histology ,endocrine system diseases ,QH573-671 ,Physiology ,High-Throughput Nucleotide Sequencing ,nutritional and metabolic diseases ,Cell Differentiation ,adipogenensis ,Cell Biology ,RC648-665 ,Diseases of the endocrine glands. Clinical endocrinology ,Mice ,Diabetes Mellitus, Type 2 ,integrated bioinformatics ,3T3-L1 Cells ,Adipocytes ,Animals ,QP1-981 ,metformin ,Cytology ,transcriptome ,Research Article ,Research Paper - Abstract
Adipose differentiation and excessive lipid accumulation are the important characteristics of obesity. Metformin, as a classic hypoglycaemic drug, has been proved to reduce body weight in type 2 diabetes, the specific mechanism has not been completely clear. A few studies have explored its effect on adipogenesis in vitro, but the existing experimental results are ambiguous. 3T3-L1 preadipocytes were used to explore the effects of metformin on the morphological and physiological changes of lipid droplets during adipogenesis. A high throughput sequencing was used to examine the effects of metformin on the transcriptome of adipogenesis. Considering the inevitable errors among independent experiments, we performed integrated bioinformatics analysis to identify important genes involved in adipogenesis and reveal potential molecular mechanisms. During the process of adipogenesis, metformin visibly relieved the morphological and functional changes. In addition, metformin reverses the expression pattern of genes related to adipogenesis at the transcriptome level. Combining with integrated bioinformatics analyses to further identify the potential targeted genes regulated by metformin during adipogenesis. The present study identified novel changes in the transcriptome of metformin in the process of adipogenesis that might shed light on the underlying mechanism by which metformin impedes the progression of obesity.
- Published
- 2022
13. Role of lncRNA LIPE-AS1 in adipogenesis
- Author
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Alyssa Thunen, Deirdre La Placa, Zhifang Zhang, and John E. Shively
- Subjects
Adipogenesis ,Histology ,QH573-671 ,long non-coding RNA ,Physiology ,CCAAT-Enhancer-Binding Protein-beta ,apoptosis ,Ceacam1 ,Cell Biology ,RC648-665 ,Diseases of the endocrine glands. Clinical endocrinology ,LIPE ,Mice ,Adipose Tissue ,Adipocytes ,QP1-981 ,Animals ,RNA, Long Noncoding ,Cytology ,Research Article ,Research Paper - Abstract
Recent studies have identified long non-coding RNAs (lncRNAs) as potential regulators of adipogenesis. In this study, we have characterized a lncRNA, LIPE-AS1, that spans genes CEACAM1 to LIPE in man with conservation of genomic organization and tissue expression between mouse and man. Tissue-specific expression of isoforms of the murine lncRNA were found in liver and adipose tissue, one of which, designated mLas-V3, overlapped the Lipe gene encoding hormone-sensitive lipase in both mouse and man suggesting that it may have a functional role in adipose tissue. Knock down of expression of mLas-V3 using anti-sense oligos (ASOs) led to a significant decrease in the differentiation of the OP9 pre-adipocyte cell line through the down regulation of the major adipogenic transcription factors Pparg and Cebpa. Knock down of mLas-V3 induced apoptosis during the differentiation of OP9 cells as shown by expression of active caspase-3, a change in the localization of LIP/LAP isoforms of C/EBPβ, and expression of the cellular stress induced factors CHOP, p53, PUMA, and NOXA. We conclude that mLas-V3 may play a role in protecting against stress associated with adipogenesis, and its absence leads to apoptosis.
- Published
- 2021
14. Licochalcone A activation of glycolysis pathway has an anti-aging effect on human adipose stem cells
- Author
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Yating Wu, Jianbo Zhu, Haitao Shen, Hao Wang, and Hailiang Liu
- Subjects
Glycyrrhiza inflata ,Aging ,Licochalcone A ,Adipose tissue ,chemistry.chemical_compound ,Chalcones ,Osteogenesis ,Humans ,Oil Red O ,Glycolysis ,Lipoprotein lipase ,Adipogenesis ,biology ,licochalcone A ,Gluconeogenesis ,Telomere Homeostasis ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,glycolysis ,biology.organism_classification ,Molecular biology ,cell proliferation ,chemistry ,adipose-derived stem cells ,Stem cell ,Reactive Oxygen Species ,Research Paper - Abstract
Licochalcone A (LA) is a chalcone flavonoid of Glycyrrhiza inflata, which has anti-cancer, antioxidant, anti-inflammatory, and neuroprotective effects. However, no anti-aging benefits of LA have been demonstrated in vitro or in vivo. In this study, we explored whether LA has an anti-aging effect in adipose-derived stem cells (ADSCs). We performed β-galactosidase staining and measured reactive oxygen species, relative telomere lengths, and P16ink4a mRNA expression. Osteogenesis was assessed by Alizarin Red staining and adipogenesis by was assessed Oil Red O staining. Protein levels of related markers runt-related transcription factor 2 and lipoprotein lipase were also examined. RNA sequencing and measurement of glycolysis activities showed that LA significantly activated glycolysis in ADSCs. Together, our data strongly suggest that the LA have an anti-aging effect through activate the glycolysis pathway.
- Published
- 2021
15. Synergetic protective effect of berberine and ginsenoside Rb1 against tumor necrosis factor alpha−induced inflammation in adipocytes
- Author
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Yue Chen and Zhixing Cai
- Subjects
obesity ,Ginsenosides ,Cell Survival ,Bioengineering ,Inflammation ,Pharmacology ,Protective Agents ,adipocyte ,Applied Microbiology and Biotechnology ,chemistry.chemical_compound ,Mice ,Berberine ,Adipocyte ,3T3-L1 Cells ,berberine ,medicine ,Adipocytes ,Animals ,nuclear factor kappa b ,Receptor ,Cell Proliferation ,Adipogenesis ,Activator (genetics) ,Tumor Necrosis Factor-alpha ,RANK Ligand ,NF-kappa B ,Drug Synergism ,General Medicine ,eye diseases ,chemistry ,inflammation ,ginsenoside rb1 ,Tumor necrosis factor alpha ,Signal transduction ,medicine.symptom ,Insulin Resistance ,TP248.13-248.65 ,Signal Transduction ,Research Article ,Research Paper ,Biotechnology - Abstract
Obesity significantly impacts living a normal life by increasing morbidity. Additionally, obesity has been shown to be closely associated with severe inflammation in adipocytes. It is widely reported that berberine (BBR) has an anti-inflammatory effect and can reduce glucose and lipid accumulation, whereas ginsenoside Rb1 (Rb1) has been shown to have a significant inhibitory effect on insulin resistance and lipid peroxidation. In this study, we aimed to explore the synergetic effect of BBR and Rb1 on tumor necrosis factor alpha (TNF-α)-treated adipocytes and the mechanisms underlying it. We found that TNF-α reduced cell viability, facilitated the production of inflammatory factors, induced adipogenesis, activated the nuclear factor kappa B (NF-κB) pathway, and increased the expression of peroxisome proliferator-activated receptor gamma, CCAAT enhancer-binding protein alpha, and sterol regulatory element-binding protein-1 c in adipocytes. However, these effects were significantly alleviated by BBR or Rb1. Additionally, a synergetic effect was observed when BBR and Rb1 were used in combination. The effects of BBR in combination with Rb1 on cell proliferation, inflammation, adipogenesis, and the NF-κB pathway in TNF-α-treated adipocytes were significantly abolished by receptor activator of nuclear factor kappa-Β ligand, which is an activator of the NF-κB pathway. Collectively, the results revealed that BBR and Rb1 have a synergetic protective effect against TNF-α-induced inflammation in adipocytes. The mechanism underlying this synergetic effect was found to be inhibition of the NF-κB signaling pathway.
- Published
- 2021
16. Increased proliferation and differentiation capacity of placenta-derived mesenchymal stem cells from women of median maternal age correlates with telomere shortening
- Author
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Erika N Guerrero, Shantal Vega, Cindy Fu, Davis Beltran, Ruth De León, and Mairim Alexandra Solis
- Subjects
Senescence ,Homeobox protein NANOG ,Adult ,Aging ,Adolescent ,proliferation ,Placenta ,Cell ,Biology ,Andrology ,Young Adult ,Pregnancy ,medicine ,telomere length ,Humans ,Telomere Shortening ,Cell Proliferation ,mesenchymal stem cells ,Cell growth ,Mesenchymal stem cell ,Cell Differentiation ,Cell Biology ,differentiation ,Telomere ,medicine.anatomical_structure ,Adipogenesis ,multipotent markers ,Female ,Research Paper ,Maternal Age - Abstract
Mesenchymal stem cells (MSCs) experience functional decline with systemic aging, resulting in reduced proliferation, increased senescence, and lower differentiation potential. The placenta represents a valuable source of MSCs, but the possible effect of donor age on the properties of placenta-derived mesenchymal stem cells (PDMSCs) has not been thoroughly studied. Thus, the aim of this study was to underscore the effect of maternal age on the biological characteristics and stemness properties of PDMSCs. PDMSCs were isolated from 5 donor age groups (A: 18-21, B: 22-25, C: 26-30, D:31-35 and E: ≥36 years) for comparison of morphological, proliferative and differentiation properties. The pluripotency markers NANOG, OCT4, and SSEA4, as well as multipotency and differentiation markers, showed higher expression in PDMSCs from mothers aged 22-35 years, with up to a 7-fold increase in adipogenesis. Cumulative population doubling, cell growth curves, and colony-forming unit-fibroblast assays revealed higher self-renewal ability in donors 26-30 years old. An increase in the proliferative characteristics of PDMSCs correlated with increased telomere shortening, suggesting that shorter telomere lengths could be related to cellular division rather than aging. A clear understanding of the effect of maternal age on MSC regenerative potential will assist in increasing the effectiveness of future cell therapies.
- Published
- 2021
17. Assessment of the disruption effects of tetrabromobisphenol A and its analogues on lipid metabolism using multiple in vitro models.
- Author
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Li Z, Liu QS, Gao Y, Wang X, Sun Z, Zhou Q, and Jiang G
- Subjects
- Animals, Mice, Humans, Hep G2 Cells, Cell Differentiation drug effects, Mesenchymal Stem Cells drug effects, Endocrine Disruptors toxicity, Adipocytes drug effects, Adipocytes metabolism, Polybrominated Biphenyls toxicity, Lipid Metabolism drug effects, 3T3-L1 Cells, Adipogenesis drug effects, Flame Retardants toxicity
- Abstract
Tetrabromobisphenol A (TBBPA), a widely-used brominated flame retardant, has been revealed to exert endocrine disrupting effects and induce adipogenesis. Given the high structural similarities of TBBPA analogues and their increasing exposure risks, their effects on lipid metabolism are necessary to be explored. Herein, 9 representative TBBPA analogues were screened for their interference on 3T3-L1 preadipocyte adipogenesis, differentiation of C3H10T1/2 mesenchymal stem cells (MSCs) to brown adipocytes, and lipid accumulation of HepG2 cells. TBBPA bis(2-hydroxyethyl ether) (TBBPA-BHEE), TBBPA mono(2-hydroxyethyl ether) (TBBPA-MHEE), TBBPA bis(glycidyl ether) (TBBPA-BGE), and TBBPA mono(glycidyl ether) (TBBPA-MGE) were found to induce adipogenesis in 3T3-L1 preadipocytes to different extends, as evidenced by the upregulated intracellular lipid generation and expressions of adipogenesis-related biomarkers. TBBPA-BHEE exhibited a stronger obesogenic effect than did TBBPA. In contrast, the test chemicals had a weak impact on the differentiation process of C3H10T1/2 MSCs to brown adipocytes. As for hepatic lipid formation test, only TBBPA mono(allyl ether) (TBBPA-MAE) was found to significantly promote triglyceride (TG) accumulation in HepG2 cells, and the effective exposure concentration of the chemical under oleic acid (OA) co-exposure was lower than that without OA co-exposure. Collectively, TBBPA analogues may perturb lipid metabolism in multiple tissues, which varies with the test tissues. The findings highlight the potential health risks of this kind of emerging chemicals in inducing obesity, non-alcoholic fatty liver disease (NAFLD) and other lipid metabolism disorders, especially under the conditions in conjunction with high-fat diets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
18. Deletion of Impdh2 in adipocyte precursors limits the expansion of white adipose tissue and enhances metabolic health with overnutrition.
- Author
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Hu J, Zheng S, Hua M, Ding M, Hu Z, and Jiang H
- Subjects
- Animals, Male, Mice, Cell Proliferation, Energy Metabolism genetics, Gene Deletion, Mice, Inbred C57BL, Mice, Knockout, Stem Cells metabolism, Stem Cells cytology, Stem Cells pathology, Adipocytes metabolism, Adipogenesis genetics, Adipose Tissue, White metabolism, Diet, High-Fat, Overnutrition metabolism, Overnutrition genetics, IMP Dehydrogenase genetics, IMP Dehydrogenase metabolism
- Abstract
The equilibrium between the hypertrophic growth of existing adipocytes and adipogenesis is vital in managing metabolic stability in white adipocytes when faced with overnutrition. Adipogenesis has been established as a key player in combating metabolic irregularities caused by various factors. However, the benefits of increasing adipogenesis-mediated white adipose tissue (WAT) expansion for metabolic health regulation remain uncertain. Our findings reveal an increase in Impdh2 expression during the adipogenesis phase, both in vivo and in vitro. Xmp enhances adipogenic potential by fostering mitotic clonal expansion (MCE). The conditional knockout of Impdh2 in adipocyte progenitor cells(APCs) in adult and aged mice effectively curbs white adipose tissue expansion, ameliorates glucose tolerance, and augments energy expenditure under high-fat diet (HFD). However, no significant difference is observed under normal chow diet (NCD). Concurrently, the knockout of Impdh2 in APCs significantly reduces the count of new adipocytes induced by HFD, without affecting adipocyte size. Mechanistically, Impdh2 regulates the proliferation of APCs during the MCE phase via Xmp. Exogenous Xmp can significantly offset the reduction in adipogenic abilities of APCs due to Impdh2 deficiency. In summary, we discovered that adipogenesis-mediated WAT expansion, induced by overnutrition, also contributes to metabolic abnormalities. Moreover, the pivotal role of Impdh2 in regulating adipogenesis in APCs offers a novel therapeutic approach to combat obesity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Haochen Jiang reports financial support was provided by National Natural Science Foundation of China. Zhangfeng Hu reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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19. Anti-adipogenic and anti-obesity effects of morroniside in vitro and in vivo.
- Author
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Oh KI, Lim E, Uprety LP, Jeong J, Jeong H, Park E, and Jeong SY
- Subjects
- Animals, Mice, Female, Adipocytes drug effects, Adipocytes metabolism, Glycosides pharmacology, Adipose Tissue drug effects, Adipose Tissue metabolism, Cell Differentiation drug effects, Mice, Obese, Triglycerides metabolism, Ovariectomy, Fatty Liver drug therapy, Adipogenesis drug effects, 3T3-L1 Cells, Obesity drug therapy, Obesity metabolism, Anti-Obesity Agents pharmacology, Diet, High-Fat adverse effects, Mice, Inbred C57BL
- Abstract
Obesity is a multifaceted medical condition characterized by the pathological accumulation of excessive lipids in the body. We investigated the effects of morroniside, a bioactive compound derived from Cornus officinalis, on adipogenesis. We used a preadipocyte 3T3-L1 stable cell line and primary cultured adipose-derived stem cells (ADSCs) in vitro and ovariectomized (OVX) and a high-fat diet (HFD)-fed obese mouse model in vivo. Preadipocyte 3T3-L1 cells and ADSCs incubated with morroniside during adipocyte differentiation and obese mice subjected to OVX and HFD received oral morroniside treatment for 12 weeks. Morroniside treatment significantly reduced adipocyte differentiation and fatty acid accumulation and downregulated adipogenesis-related gene expression, concomitant with a decrease in triglyceride content and an increase in glycerol release in cells. The results of the in vivo study showed that morroniside ameliorated obesity-related phenotypes by reducing body weight gain, hepatic steatosis, and adipose tissue in obese mice. These findings suggest that morroniside is a promising compound for preventing and treating obesity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Seon-Yong Jeong reports financial support was provided by Ministry of Health & Welfare, Republic of Korea. Eunkuk Park reports financial support was provided by Ministry of SMEs and Startups. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
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20. AN698/40746067 suppresses bone marrow adiposity to ameliorate hyperlipidemia-induced osteoporosis through targeted inhibition of ENTR1.
- Author
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Ren H, Mao K, Yuan X, Mu Y, Zhao S, Fan X, Zhu L, Ye Z, and Lan J
- Subjects
- Animals, Male, Mice, Adiposity drug effects, Endosomal Sorting Complexes Required for Transport metabolism, Mice, Inbred C57BL, Adipogenesis drug effects, Bone Marrow metabolism, Bone Marrow drug effects, Hyperlipidemias drug therapy, Hyperlipidemias metabolism, Mesenchymal Stem Cells drug effects, Mesenchymal Stem Cells metabolism, Osteoporosis drug therapy, Osteoporosis metabolism, Osteoporosis etiology, Osteoporosis prevention & control, PPAR gamma metabolism
- Abstract
Hyperlipidemia-induced osteoporosis is marked by increased bone marrow adiposity, and treatment with statins for hyperlipidemia often leads to new-onset osteoporosis. Endosome-associated trafficking regulator 1 (ENTR1) has been found to interact with different proteins in pathophysiology, but its exact role in adipogenesis is not yet understood. This research aimed to explore the role of ENTR1 in adipogenesis and to discover a new small molecule that targets ENTR1 for evaluating its effectiveness in treating hyperlipidemia-induced osteoporosis. We found that ENTR1 expression increased during the adipogenesis of bone marrow mesenchymal cells (BMSCs). ENTR1 gain- and loss-of-function assays significantly enhanced lipid droplets formation. Mechanistically, ENTR1 binds peroxisome proliferator-activated receptor γ (PPARγ) and enhances its expression, thereby elevating adipogenic markers including C/EBPα and LDLR. Therapeutically, AN698/40746067 attenuated adipogenesis by targeting ENTR1 to suppress PPARγ. In vivo, AN698/40746067 reduced bone marrow adiposity and bone loss, as well as prevented lipogenesis-related obesity, inflammation, steatohepatitis, and abnormal serum lipid levels during hyperlipidemia. Together, these findings suggest that ENTR1 facilitates adipogenesis by PPARγ involved in BMSCs' differentiation, and targeted inhibition of ENTR1 by AN698/40746067 may offer a promising therapy for addressing lipogenesis-related challenges and alleviating osteoporosis following hyperlipidemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
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21. Metabolomics in human SGBS cells as new approach method for studying adipogenic effects: Analysis of the effects of DINCH and MINCH on central carbon metabolism.
- Author
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Goerdeler C, Engelmann B, Aldehoff AS, Schaffert A, Blüher M, Heiker JT, Wabitsch M, Schubert K, Rolle-Kampczyk U, and von Bergen M
- Subjects
- Humans, Carbon metabolism, Cell Line, Plasticizers toxicity, Metabolomics methods, Dicarboxylic Acids pharmacology, Dicarboxylic Acids metabolism, Adipogenesis drug effects, Adipocytes drug effects, Adipocytes metabolism, Cyclohexanecarboxylic Acids pharmacology
- Abstract
Growing evidence suggests that exposure to certain metabolism-disrupting chemicals (MDCs), such as the phthalate plasticizer DEHP, might promote obesity in humans, contributing to the spread of this global health problem. Due to the restriction on the use of phthalates, there has been a shift to safer declared substitutes, including the plasticizer diisononyl-cyclohexane-1,2-dicarboxylate (DINCH). Notwithstanding, recent studies suggest that the primary metabolite monoisononyl-cyclohexane-1,2-dicarboxylic acid ester (MINCH), induces differentiation of human adipocytes and affects enzyme levels of key metabolic pathways. Given the lack of methods for assessing metabolism-disrupting effects of chemicals on adipose tissue, we used metabolomics to analyze human SGSB cells exposed to DINCH or MINCH. Concentration analysis of DINCH and MINCH revealed that uptake of MINCH in preadipocytes was associated with increased lipid accumulation during adipogenesis. Although we also observed intracellular uptake for DINCH, the solubility of DINCH in cell culture medium was limited, hampering the analysis of possible effects in the μM concentration range. Metabolomics revealed that MINCH induces lipid accumulation similar to peroxisome proliferator-activated receptor gamma (PPARG)-agonist rosiglitazone through upregulation of the pyruvate cycle, which was recently identified as a key driver of de novo lipogenesis. Analysis of the metabolome in the presence of the PPARG-inhibitor GW9662 indicated that the effect of MINCH on metabolism was mediated at least partly by a PPARG-independent mechanism. However, all effects of MINCH were only observed at high concentrations of 10 μM, which are three orders of magnitudes higher than the current concentrations of plasticizers in human serum. Overall, the assessment of the effects of DINCH and MINCH on SGBS cells by metabolomics revealed no adipogenic potential at physiologically relevant concentrations. This finding aligns with previous in vivo studies and supports the potential of our method as a New Approach Method (NAM) for the assessment of adipogenic effects of environmental chemicals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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22. Anti-obesity effects of Celosia cristata flower extract in vitro and in vivo.
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Uprety LP, Lee CG, Oh KI, Jeong H, Yeo S, Yong Y, Seong JK, Kim IY, Go H, Park E, and Jeong SY
- Subjects
- Animals, Male, Mice, Adipose Tissue drug effects, Adipose Tissue metabolism, Lipid Metabolism drug effects, Lipolysis drug effects, Cell Differentiation drug effects, Plant Extracts pharmacology, Plant Extracts isolation & purification, 3T3-L1 Cells, Mice, Inbred C57BL, Anti-Obesity Agents pharmacology, Anti-Obesity Agents isolation & purification, Flowers chemistry, Adipogenesis drug effects, Obesity drug therapy, Obesity metabolism, Diet, High-Fat adverse effects, Adipocytes drug effects, Adipocytes metabolism, Celosia chemistry
- Abstract
Background: The overstoring of surplus calories in mature adipocytes causes obesity and abnormal metabolic activity. The anti-obesity effect of a Celosia cristata (CC) total flower extract was assessed in vitro, using 3T3-L1 pre-adipocytes and mouse adipose-derived stem cells (ADSCs), and in vivo, using high-fat diet (HFD)-treated C57BL/6 male mice., Methods: CC extract was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs. After differentiation, lipid droplets were assessed by oil red O staining, adipogenesis and lipolytic factors were evaluated, and intracellular triglyceride and glycerol concentrations were analyzed. For in vivo experiments, histomorphological analysis, mRNA expression levels of adipogenic and lipolytic factors in adipose tissue, blood plasma analysis, metabolic profiles were investigated., Results: CC treatment significantly prevented adipocyte differentiation and lipid droplet accumulation, reducing adipogenesis-related factors and increasing lipolysis-related factors. Consequently, the intracellular triacylglycerol content was diminished, whereas the glycerol concentration in the cell supernatant increased. Mice fed an HFD supplemented with the CC extract exhibited decreased HFD-induced weight gain with metabolic abnormalities such as intrahepatic lipid accumulation and adipocyte hypertrophy. Improved glucose utilization and insulin sensitivity were observed, accompanied by the amelioration of metabolic disturbances, including alterations in liver enzymes and lipid profiles, in CC-treated mice. Moreover, the CC extract helped restore the disrupted energy metabolism induced by the HFD, based on a metabolic animal monitoring system., Conclusion: This study suggests that CC total flower extract is a potential natural herbal supplement for the prevention and management of obesity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Seon-Yong Jeong reports financial support was provided by Ministry of Health & Welfare, Republic of Korea. Eunkuk Park reports financial support was provided by Ministry of SMEs and Startups. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
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23. Effects of an environmentally relevant mixture of organochlorine pesticide compounds on adipogenesis and adipocyte function in an immortalized human adipocyte model.
- Author
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Howell GE 3rd and Young D
- Subjects
- Humans, Cytokines metabolism, Membrane Potential, Mitochondrial drug effects, Glucose metabolism, Adenosine Triphosphate metabolism, Cell Line, Fatty Acids, Staphylococcus aureus drug effects, Environmental Pollutants toxicity, Hydrocarbons, Chlorinated toxicity, Pesticides toxicity, Adipogenesis drug effects, Adipocytes drug effects
- Abstract
Exposure to persistent organic pollutants (POPs), including organochlorine (OC) pesticide POPs, has been associated with the increased prevalence of obesity and type 2 diabetes. However, the underlying mechanisms through which exposure to these compounds may promote obesity and metabolic dysfunction remain an area of active investigation. To this end, the concentration dependent effects of an environmentally relevant mixture of OC pesticide POPs on adipocyte function was explored utilizing a translationally relevant immortalized human subcutaneous preadipocyte/adipocyte model. Briefly, immortalized human preadipocytes/adipocytes were exposed to a mixture of dichlorodiphenyldichloroethylene (DDE), trans-nonachlor, and oxychlordane (DTO) then key indices of preadipocyte/adipocyte function were assessed. Exposure to DTO did not alter adipogenesis. However, in mature adipocytes, exposure to DTO slightly increased fatty acid uptake whereas isoproterenol stimulated lipolysis, basal and insulin stimulated glucose uptake, mitochondrial membrane potential, and cellular ATP levels were all significantly decreased. DTO significantly increased Staphylococcus aureus infection induced increases in expression of pro-inflammatory cytokines IL-6, IL-1β, and Mcp-1 as well as the adipokine resistin. Taken together, the present data demonstrated exposure to an environmentally relevant mixture of OC pesticide compounds can alter mature adipocyte function in a translationally relevant human adipocyte model which further supports the adipose tissue as an effector site of OC pesticide POPs action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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24. M2 macrophage-derived TGF-β induces age-associated loss of adipogenesis through progenitor cell senescence.
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Zeng X, Wang TW, Yamaguchi K, Hatakeyama S, Yamazaki S, Shimizu E, Imoto S, Furukawa Y, Johmura Y, and Nakanishi M
- Subjects
- Animals, Mice, Humans, Mice, Inbred C57BL, Aging metabolism, Male, Adipocytes metabolism, Adipose Tissue, White metabolism, Cellular Senescence, Adipogenesis, Macrophages metabolism, Transforming Growth Factor beta metabolism, Stem Cells metabolism
- Abstract
Objectives: Adipose tissue is an endocrine and energy storage organ composed of several different cell types, including mature adipocytes, stromal cells, endothelial cells, and a variety of immune cells. Adipose tissue aging contributes to the pathogenesis of metabolic dysfunction and is likely induced by crosstalk between adipose progenitor cells (APCs) and immune cells, but the underlying molecular mechanisms remain largely unknown. In this study, we revealed the biological role of p16
high senescent APCs, and investigated the crosstalk between each cell type in the aged white adipose tissue., Methods: We performed the single-cell RNA sequencing (scRNA-seq) analysis on the p16high adipose cells sorted from aged p16-CreERT2 /Rosa26-LSL-tdTomato mice. We also performed the time serial analysis on the age-dependent bulk RNA-seq datasets of human and mouse white adipose tissues to infer the transcriptome alteration of adipogenic potential within aging., Results: We show that M2 macrophage-derived TGF-β induces APCs senescence which impairs adipogenesis in vivo. p16high senescent APCs increase with age and show loss of adipogenic potential. The ligand-receptor interaction analysis reveals that M2 macrophages are the donors for TGF-β and the senescent APCs are the recipients. Indeed, treatment of APCs with TGF-β1 induces senescent phenotypes through mitochondrial ROS-mediated DNA damage in vitro. TGF-β1 injection into gonadal white adipose tissue (gWAT) suppresses adipogenic potential and induces fibrotic genes as well as p16 in APCs. A gWAT atrophy is observed in cancer cachexia by APCs senescence, whose induction appeared to be independent of TGF-β induction., Conclusions: Our results suggest that M2 macrophage-derived TGF-β induces age-related lipodystrophy by APCs senescence. The TGF-β treatment induced DNA damage, mitochondrial ROS, and finally cellular senescence in APCs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Makoto Nakanishi reports financial support was provided by Japan Society for the Promotion of Science. Makoto Nakanishi reports financial support was provided by Japan Agency for Medical Research and Development. Yoshikazu Johmura reports financial support was provided by Japan Society for the Promotion of Science. Yoshikazu Johmura reports financial support was provided by Japan Agency for Medical Research and Development. Makoto Nakanishi reports a relationship with reverSASP Therapeutics that includes: consulting or advisory. Satoshi Yamazaki reports a relationship with Celaid Therapeutics that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)- Published
- 2024
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25. TAT38 and TAT38 mimics potently inhibit adipogenesis by repressing C/EBPα, PPARγ, Pi-PPARγ, and SREBP1 expression.
- Author
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Park SY, Shin D, Yoon YS, Park S, Im SS, Kim Y, Kim YS, Choi C, and Hur MW
- Subjects
- Animals, Mice, CCAAT-Enhancer-Binding Protein-alpha metabolism, CCAAT-Enhancer-Binding Protein-alpha genetics, 3T3-L1 Cells, Humans, Gene Expression Regulation, Mice, Obese, Male, Cyclin T metabolism, Obesity metabolism, Adipocytes metabolism, Mice, Inbred C57BL, CCAAT-Enhancer-Binding Proteins, PPAR gamma metabolism, Adipogenesis drug effects, Sterol Regulatory Element Binding Protein 1 metabolism, Sterol Regulatory Element Binding Protein 1 genetics, tat Gene Products, Human Immunodeficiency Virus metabolism, tat Gene Products, Human Immunodeficiency Virus genetics
- Abstract
Antiretroviral therapy-naive people living with HIV possess less fat than people without HIV. Previously, we found that HIV-1 transactivator of transcription (TAT) decreases fat in ob/ob mice. The TAT38 (a.a. 20-57) is important in the inhibition of adipogenesis and contains three functional domains: Cys-ZF domain (a.a. 20-35 TACTNCYCAKCCFQVC), core-domain (a.a. 36-46, FITKALGISYG), and protein transduction domain (PTD)(a.a. 47-57, RAKRRQRRR). Interestingly, the TAT38 region interacts with the Cyclin T1 of the P-TEFb complex, of which expression increases during adipogenesis. The X-ray crystallographic structure of the complex showed that the Cys-ZF and the core domain bind to the Cyclin T1 via hydrophobic interactions. To prepare TAT38 mimics with structural and functional similarities to TAT38, we replaced the core domain with a hydrophobic aliphatic amino acid (from carbon numbers 5 to 8). The TAT38 mimics with 6-hexanoic amino acid (TAT38 Ahx (C6)) and 7-heptanoic amino acid (TAT38 Ahp (C7)) inhibited adipogenesis of 3T3-L1 potently, reduced cellular triglyceride content, and decreased body weight of diet-induced obese (DIO) mice by 10.4-11 % in two weeks. The TAT38 and the TAT38 mimics potently repressed the adipogenic transcription factors genes, C/EBPα, PPARγ, and SREBP1. Also, they inhibit the phosphorylation of PPARγ. The TAT peptides may be promising candidates for development into a drug against obesity or diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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26. Development of piperine nanoparticles stabilized by OSA modified starch through wet-media milling technique with enhanced anti-adipogenic effect in 3T3-L1 adipocytes.
- Author
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Tang B, Sun J, Xiao J, Cao Y, Huang Q, Ho CT, Kou X, and Lu M
- Subjects
- Animals, Mice, Particle Size, Drug Liberation, Cell Differentiation drug effects, 3T3-L1 Cells, Nanoparticles chemistry, Polyunsaturated Alkamides chemistry, Polyunsaturated Alkamides pharmacology, Benzodioxoles pharmacology, Benzodioxoles chemistry, Piperidines pharmacology, Piperidines chemistry, Adipogenesis drug effects, Alkaloids chemistry, Alkaloids pharmacology, Adipocytes drug effects, Starch chemistry, Starch analogs & derivatives
- Abstract
Piperine (PIP) has been known for its pharmacological activities with low water solubility and poor dissolution, which limits its nutritional application. The purpose of this research was to enhance PIP stability, dispersibility and biological activity by preparing PIP nanoparticles using the wet-media milling approach combined with nanosuspension solidification methods of spray/freeze drying. Octenyl succinic anhydride (OSA)-modified waxy maize starch was applied as the stabilizer to suppress aggregation of PIP nanoparticles. The particle size, redispersibility, storage stability and in vitro release behavior of PIP nanoparticles were measured. The regulating effect on adipocyte differentiation was evaluated using 3T3-L1 cell model. Results showed that PIP nanoparticles had a reduced particle size of 60 ± 1 nm, increased release rate in the simulated gastric (SGF) and intestinal fluids (SIF) and enhanced inhibition effect on adipogenesis in 3T3-L1 cells compared with free PIP, indicating that PIP-loaded nanoparticles with improved stability and anti-adipogenic property were developed successfully by combining wet-media milling and drying methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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27. A review of the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle.
- Author
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Abebe BK, Wang H, Li A, and Zan L
- Subjects
- Cattle genetics, Animals, Transcription Factors genetics, Transcription Factors metabolism, Epigenesis, Genetic, Adipose Tissue metabolism, Muscle, Skeletal metabolism, Lipogenesis genetics, Adipogenesis genetics
- Abstract
In the past few decades, genomic selection and other refined strategies have been used to increase the growth rate and lean meat production of beef cattle. Nevertheless, the fast growth rates of cattle breeds are often accompanied by a reduction in intramuscular fat (IMF) deposition, impairing meat quality. Transcription factors play vital roles in regulating adipogenesis and lipogenesis in beef cattle. Meanwhile, understanding the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle has gained significant attention to increase IMF deposition and meat quality. Therefore, the aim of this paper was to provide a comprehensive summary and valuable insight into the complex role of transcription factors in adipogenesis and lipogenesis in beef cattle. This review summarizes the contemporary studies in transcription factors in adipogenesis and lipogenesis, genome-wide analysis of transcription factors, epigenetic regulation of transcription factors, nutritional regulation of transcription factors, metabolic signalling pathways, functional genomics methods, transcriptomic profiling of adipose tissues, transcription factors and meat quality and comparative genomics with other livestock species. In conclusion, transcription factors play a crucial role in promoting adipocyte development and fatty acid biosynthesis in beef cattle. They control adipose tissue formation and metabolism, thereby improving meat quality and maintaining metabolic balance. Understanding the processes by which these transcription factors regulate adipose tissue deposition and lipid metabolism will simplify the development of marbling or IMF composition in beef cattle., (© 2023 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)
- Published
- 2024
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28. Dysregulation of adipogenesis and disrupted lipid metabolism by the antidepressants citalopram and sertraline.
- Author
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Bozdag D, van Voorthuizen J, Korpel N, Lentz S, Gurer-Orhan H, and Kamstra JH
- Subjects
- Humans, Adipocytes drug effects, Adipocytes metabolism, Cells, Cultured, Dose-Response Relationship, Drug, Adipogenesis drug effects, Sertraline pharmacology, Sertraline toxicity, Citalopram pharmacology, Lipid Metabolism drug effects, Mesenchymal Stem Cells drug effects, Mesenchymal Stem Cells metabolism, Selective Serotonin Reuptake Inhibitors pharmacology, Selective Serotonin Reuptake Inhibitors toxicity, Antidepressive Agents pharmacology
- Abstract
Selective Serotonin Reuptake Inhibitors (SSRIs) are widely used medications for the treatment of major depressive disorder. However, long-term SSRI use has been associated with weight gain and altered lipid profiles. These findings suggest that SSRIs may have negative effects on metabolism. Exposure to certain chemicals called 'obesogens' is known to promote lipid accumulation and obesity by modulating adipogenesis. Here, we investigated whether citalopram (CIT) and sertraline (SER) interfere with the process of adipogenesis, using human mesenchymal stem cells (MSCs) in a 2D and a 3D model. Assessment of intracellular lipid accumulation by fluorescence staining was used as a measure for enhanced adipogenesis. To explore possible mechanisms behind SSRIs' effects, receptor mediated activity was studied using responsive cell lines for various nuclear receptors. Furthermore, RNA sequencing was performed in the 3D model, followed by differential gene expression and pathway analysis. A dose dependent increase in lipid accumulation was observed in both models with CIT and SER. For the 3D model, the effect was seen in a range close to reported steady-state plasma concentrations (0.065-0.65 μM for SER and 0.12-0.92 μM for CIT). Pathway analysis revealed unexpected results of downregulation in adipogenesis-related pathways and upregulation in phospholipids and lysosomal pathways. This was confirmed by an observed increase in lysosomes in the 2D model. Our findings suggest lysosomal dysfunction and disrupted lipid metabolism in mature adipocytes, leading to excessive phospholipid synthesis. Moreover, important adipogenic processes are inhibited, potentially leading to dysfunctional adipocytes, which might have implications in the maintenance of a healthy metabolic balance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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29. Long non-coding RNA (LncRNA) and epigenetic factors: their role in regulating the adipocytes in bovine.
- Author
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Diba Dedacha Jilo, Abebe, Belete Kuraz, Jianfang Wang, Juntao Guo, Anning Li, and Linsen Zan
- Subjects
GENETIC regulation ,GENETIC variation ,ADIPOGENESIS ,REGULATOR genes ,CELL physiology ,GENETIC markers ,LINCRNA ,GENE enhancers - Abstract
Investigating the involvement of long non-coding RNAs (lncRNAs) and epigenetic processes in bovine adipocytes can provide valuable new insights into controlling adipogenesis in livestock. Long non-coding RNAs have been associated with forming chromatin loops that facilitate enhancer-promoter interactions during adipogenesis, as well as regulating important adipogenic transcription factors like C/EBPa and PPARγ. They significantly influence gene expression regulation at the post-transcriptional level and are extensively researched for their diverse roles in cellular functions. Epigenetic modifications such as chromatin reorganization, histone alterations, and DNA methylation subsequently affect the activation of genes related to adipogenesis and the progression of adipocyte differentiation. By investigating how fat deposition is epigenetically regulated in beef cattle, scientists aim to unravel molecular mechanisms, identify key regulatory genes and pathways, and develop targeted strategies for modifying fat deposition to enhance desirable traits such as marbling and meat tenderness. This review paper delves into lncRNAs and epigenetic factors and their role in regulating bovine adipocytes while focusing on their potential as targets for genetic improvement to increase production efficiency. Recent genomics advancements, including molecular markers and genetic variations, can boost animal productivity, meeting global demands for high-quality meat products. This review establishes a foundation for future research on understanding regulatory networks linked to lncRNAs and epigenetic changes, contributing to both scholarly knowledge advancement and practical applications within animal agriculture. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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30. Single-cell RNA sequencing deconvolutes the in vivo heterogeneity of human bone marrow-derived mesenchymal stem cells
- Author
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Hong-Wen Deng, Yun Gong, Zun Wang, Li-Jun Tan, Yang Junxiao, Yiping Chen, Xiang Qiu, Cui Zhou, Liang Cheng, Jonathan Greenbaum, Siyuan Tang, Hong-Mei Xiao, Yusheng Li, Martin R. Schiller, Xiaohua Li, Yu Chen, Huixi Zhang, Yihe Hu, Hui Shen, Yang Xucheng, Ying Liu, and Jie Xie
- Subjects
Male ,Stromal cell ,bone marrow ,Bone Marrow Cells ,Nerve Tissue Proteins ,Receptors, Nerve Growth Factor ,Biology ,Muscle Development ,Applied Microbiology and Biotechnology ,Chondrocyte ,osteogenesis ,adipogenesis ,Mice ,Chondrocytes ,Bone Density ,chondrogenesis ,medicine ,Animals ,Cluster Analysis ,Humans ,Molecular Biology ,single-cell RNA sequencing (scRNA-seq) ,Ecology, Evolution, Behavior and Systematics ,Aged ,Aged, 80 and over ,Cluster of differentiation ,mesenchymal stem cell (MSC) ,Sequence Analysis, RNA ,Mesenchymal stem cell ,Osteoblast ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,CD56 Antigen ,Cell biology ,Mice, Inbred C57BL ,Haematopoiesis ,medicine.anatomical_structure ,Gene Expression Regulation ,Osteocyte ,Female ,Bone marrow ,Single-Cell Analysis ,Developmental Biology ,Research Paper - Abstract
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells that have a critical role in the maintenance of skeletal tissues such as bone, cartilage, and the fat in bone marrow. In addition to providing microenvironmental support for hematopoietic processes, BM-MSCs can differentiate into various mesodermal lineages including osteoblast/osteocyte, chondrocyte, and adipocyte that are crucial for bone metabolism. While BM-MSCs have high cell-to-cell heterogeneity in gene expression, the cell subtypes that contribute to this heterogeneity in vivo in humans have not been characterized. To investigate the transcriptional diversity of BM-MSCs, we applied single-cell RNA sequencing (scRNA-seq) on freshly isolated CD271+ BM-derived mononuclear cells (BM-MNCs) from two human subjects. We successfully identified LEPRhiCD45low BM-MSCs within the CD271+ BM-MNC population, and further codified the BM-MSCs into distinct subpopulations corresponding to the osteogenic, chondrogenic, and adipogenic differentiation trajectories, as well as terminal-stage quiescent cells. Biological functional annotations of the transcriptomes suggest that osteoblast precursors induce angiogenesis coupled with osteogenesis, and chondrocyte precursors have the potential to differentiate into myocytes. We also discovered transcripts for several clusters of differentiation (CD) markers that were either highly expressed (e.g., CD167b, CD91, CD130 and CD118) or absent (e.g., CD74, CD217, CD148 and CD68) in BM-MSCs, representing potential novel markers for human BM-MSC purification. This study is the first systematic in vivo dissection of human BM-MSCs cell subtypes at the single-cell resolution, revealing an insight into the extent of their cellular heterogeneity and roles in maintaining bone homeostasis.
- Published
- 2021
31. Differential regulatory roles of microRNAs during intramuscular adipogenesis in Chinese Guizhou Congjiang Xiang pigs
- Author
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Lulin Tan, Zhaojun Chen, Yong Ruan, and Houqiang Xu
- Subjects
Cancer Research ,China ,Adipogenesis ,Swine ,AMP-Activated Protein Kinases ,DNA Methylation ,Lipids ,MicroRNAs ,Phosphatidylinositol 3-Kinases ,Animals ,Luciferases ,Molecular Biology ,Proto-Oncogene Proteins c-akt ,Research Paper ,Cell Proliferation - Abstract
Intramuscular fat development is regulated by a series of complicated processes, with non-coding RNA (ncRNA) such as microRNA (miRNA) having a critical role during intramuscular preadipocyte proliferation and differentiation in pigs. In the present study, the miRNA expression profiles of intramuscular preadipocytes from the longissimus dorsi muscle of Chinese Guizhou Congjiang Xiang pigs were detected by RNA-seq during various differentiation stages, namely, day 0 (D0), day 4 (D4), and day 8 (D8). A total of 67, 95, and 16 differentially expressed (DE) miRNAs were detected between D4 and D0, D8 and D0, and D8 and D4, respectively. According to gene ontology and Kyoto Encyclopedia of Genes analysis, target genes of DE miRNAs were enriched in categories and pathways related to lipid metabolic process, lipid biosynthetic process, as well as the PI3K-Akt, AMPK, and MAPK signalling pathways. Notably, miR-148a-3p was differentially expressed, with highest expressed abundance in D0, D4, and D8. Overexpression of miR-148a-3p in intramuscular preadipocytes increased cell proliferation and differentiation, and decreased apoptosis, in comparison to the knockdown of miR-148a-3p in intramuscular preadipocytes. Luciferase activity assays, quantitative polymerase-chain reaction, and western blot analysis confirmed that miR-148a-3p regulated adipogenesis by repressing PPARGC1A expression. Accordingly, the effect of miR-148a-3p mimic was attenuated by overexpression of PPARGC1A intramuscular preadipocytes. Furthermore, miR-148a-3p promoted intramuscular preadipocyte differentiation by inhibiting the AMPK/ACC/CPT1C signalling pathway. Taken together, we identified expression profiles of miRNAs in intramuscular preadipocytes and determined that miR-148a-3p acted as a promoter of adipogenesis.
- Published
- 2022
32. Silencing ANGPTL8 reduces mouse preadipocyte differentiation and insulin signaling.
- Author
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Ghosh A, Leung YH, Yu J, Sladek R, Chénier I, Oppong AK, Peyot ML, Madiraju SRM, Al-Khairi I, Thanaraj TA, Abubaker J, Al-Mulla F, Prentki M, and Abu-Farha M
- Subjects
- Mice, Animals, Cell Differentiation genetics, Signal Transduction, RNA, Small Interfering, Angiopoietin-Like Protein 8, Insulin, Adipogenesis genetics
- Abstract
ANGPTL8, expressed mainly in the liver and adipose tissue, regulates the activity of lipoprotein lipase (LPL) present in the extracellular space and triglyceride (TG) metabolism through its interaction with ANGPTL3 and ANGPTL4. Whether intracellular ANGPTL8 can also exert effects in tissues where it is expressed is uncertain. ANGPTL8 expression was low in preadipocytes and much increased during differentiation. To better understand the role of intracellular ANGPTL8 in adipocytes and assess whether it may play a role in adipocyte differentiation, we knocked down its expression in normal mouse subcutaneous preadipocytes. ANGPTL8 knockdown reduced adipocyte differentiation, cellular TG accumulation and also isoproterenol-stimulated lipolysis at day 7 of differentiation. RNA-Seq analysis of ANGPTL8 siRNA or control siRNA transfected SC preadipocytes on days 0, 2, 4 and 7 of differentiation showed that ANGPTL8 knockdown impeded the early (day 2) expression of adipogenic and insulin signaling genes, PPARγ, as well as genes related to extracellular matrix and NF-κB signaling. Insulin mediated Akt phosphorylation was reduced at an early stage during adipocyte differentiation. This study based on normal primary cells shows that ANGPTL8 has intracellular actions in addition to effects in the extracellular space, like modulating LPL activity. Preadipocyte ANGPTL8 expression modulates their differentiation possibly via changes in insulin signaling gene expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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33. Perturbation of lipid metabolism in 3T3-L1 at different stages of preadipocyte differentiation and new insights into the association between changed metabolites and adipogenesis promoted by TBBPA or TBBPS.
- Author
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Yu YJ, Tian JL, Zheng T, Kuang HX, Li ZR, Hao CJ, Xiang MD, and Li ZC
- Subjects
- Animals, Mice, 3T3-L1 Cells, Cell Differentiation, Glycerophospholipids pharmacology, Adipogenesis, Lipid Metabolism, Polybrominated Biphenyls
- Abstract
Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) are widely distributed brominated flame retardants. While TBBPA has been demonstrated to stimulate adipogenesis, TBBPS is also under suspicion for potentially inducing comparable effects. In this study, we conducted a non-targeted metabolomics to examine the metabolic changes in 3T3-L1 cells exposed to an environmentally relevant dose of TBBPA or TBBPS. Our findings revealed that 0.1 µM of both TBBPA and TBBPS promoted the adipogenesis of 3T3-L1 preadipocytes. Multivariate analysis showed significant increases in glycerophospholipids, sphingolipids, and steroids relative levels in 3T3-L1 cells exposed to TBBPA or TBBPS at the final stage of preadipocyte differentiation. Metabolites set composed of glycerophospholipids was found to be highly effective predictors of adipogenesis in 3T3-L1 cells exposed to TBBPA or TBBPS (revealed from the receiver operating characteristic curve with an area under curve > 0.90). The results from metabolite set enrichment analysis suggested both TBBPA and TBBPS exposures significantly perturbed steroid biosynthesis in adipocytes. Moreover, TBBPS additionally disrupted the sphingolipid metabolism in the adipocytes. Our study presents new insights into the obesogenic effects of TBBPS and provides valuable information about the metabolites associated with adipogenesis induced by TBBPA or TBBPS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2024
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34. The inhibitory effects of Xiao-Gao-Jiang-Zhuo-containing serum on adipogenesis in 3T3-L1 preadipocytes.
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Chen L, Han Y, Li J, Feng C, Chen C, and Ye T
- Subjects
- Humans, Mice, Rats, Animals, 3T3-L1 Cells, Obesity, Triglycerides, Transcription Factors, PPAR gamma metabolism, Adipogenesis, Glycerol metabolism, Glycerol pharmacology
- Abstract
Background: Obesity and related metabolic diseases are becoming a worldwide epidemic, leading to increased mortality and heavy medical costs. Our Chinese herbal formula Xiao-Gao-Jiang-Zhuo (XGJZ) has remarkable effects on curing obese patients in the clinic, but the cellular and molecular basis remains unknown. This study aimed to reveal the molecular mechanism involved in adipogenesis in vitro., Methods: Chinese herbal formula XGJZ-containing serum was prepared from XGJZ-treated obesity model rats. The function of XGJZ-containing serum was validated in 3T3-L1 preadipocytes. Oil O staining was performed to determine intracellular lipid accumulation in differentiated 3T3-L1 cells. The expression of pro-adipogenic transcription factors was measured to further validate the adipogenesis of 3T3-L1 adipocytes. The contents of triglyceride (TG), free fatty acid (FFA), and glycerin, along with the activities of lipid metabolism-related enzymes (including FAT, FATP1, DGAT, GPAT, ATGL, and HSL) were measured to study the lipogenesis in 3T3-L1 adipocytes., Results: XGJZ-containing serum inhibited 3T3-L1 differentiation, decreased intracellular lipid accumulation, and suppressed the expression of pro-adipogenic transcription factors in differentiated 3T3-L1 cells. The contents of TG, FFA, and glycerin were decreased when treated with XGJZ-containing serum, which also modulated lipid metabolism-related enzyme activities. The activities of fatty acid transporters (FAT, FATP1) and lipid mobilization enzymes (ATGL, HSL) were promoted, while activities of triglyceride biosynthesis enzymes (DGAT, GPAT) were attenuated in differentiated 3T3-L1 cells., Conclusion: XGJZ-containing serum has inhibitory effects on adipogenesis in 3T3-L1 preadipocytes, affirming the effect of XGJZ in treating obesity. It provides evidence for the mechanism of obesity., Competing Interests: The authors report no conflicts of interest in this work.
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- 2024
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35. Sesamin and sesamolin potentially inhibit adipogenesis through downregulating the peroxisome proliferator-activated receptor γ protein expression and activity in 3T3-L1 cells.
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Gina NNT, Kuo JL, Wu ML, and Chuang SM
- Subjects
- Animals, Mice, PPAR gamma genetics, PPAR gamma metabolism, 3T3-L1 Cells, Adipocytes, Cell Differentiation, CCAAT-Enhancer-Binding Protein-alpha metabolism, Mitogen-Activated Protein Kinases metabolism, Adipogenesis, Lignans pharmacology, Dioxoles
- Abstract
Sesamin and sesamolin are major sesame lignans that have demonstrated anti-inflammatory, anticancer, and neuroprotective properties and potential benefits in the liver, cardiovascular diseases, and metabolic syndrome. However, despite previous research on their antiobesity effects and underlying mechanisms, a comprehensive investigation of these aspects is still lacking. In this study, we evaluated the regulatory effects of 20 to 80 µM sesamin and sesamolin on adipogenesis in vitro using 3T3-L1 cells as a model cell line. We hypothesized that the lignans would inhibit adipogenic differentiation in 3T3-L1 cells through the regulation of peroxisome proliferator-activated receptor γ (PPARγ). Our data indicate that sesamin and sesamolin inhibited the adipogenic differentiation of 3T3-L1 cells by dose-dependently decreasing lipid accumulation and triglyceride formation. Sesamin and sesamolin reduced the mRNA and protein expression of the adipogenesis-related transcription factors, PPARγ and CCAAT/enhancer-binding protein α, leading to the dose-dependent downregulations of their downstream targets, fatty acid binding protein 4, hormone-sensitive lipase, lipoprotein lipase, and glucose transporter 4. In addition, glucose uptake was dose-dependently attenuated by sesamin and sesamolin in both differentiated 3T3-L1 cells and HepG2 cells. Interestingly, our results suggested that sesamin and sesamolin might directly bind to PPARγ to inhibit its transcriptional activity. Finally, sesamin and sesamolin decreased the phosphorylation of 3 mitogen-activated protein kinase signaling components in differentiated 3T3-L1 cells. Taken together, our findings suggest that sesamin and sesamolin may exhibit antiobesity effects by potentially downregulating PPARγ and its downstream genes through the mitogen-activated protein kinase signaling pathway, offering important insights into the molecular mechanisms underlying the potential antiobesity effects of sesamin and sesamolin., Competing Interests: Declaration of competing interest The authors state that they do not have any known financial interests or personal relationships that could have influenced the findings of this paper., (Copyright © 2023. Published by Elsevier Inc.)
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- 2024
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36. Enhancer-mediated FOXO3 expression promotes MSC adipogenic differentiation by activating autophagy.
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Feng P, Pang P, Sun Z, Xie Z, Chen T, Wang S, Cao Q, Mi R, Zeng C, Lu Y, Yu W, Shen H, and Wu Y
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- Humans, Proto-Oncogene Proteins c-akt genetics, PPAR gamma metabolism, Phosphatidylinositol 3-Kinases genetics, Forkhead Box Protein O3 genetics, Transcription Factors, Autophagy genetics, Adipogenesis genetics, Osteoporosis
- Abstract
Background: Mesenchymal stem cells (MSCs) are pluripotent stem cells capable of differentiating into osteocytes, adipocytes and chondrocytes. However, in osteoporosis, the balance of differentiation is tipped toward adipogenesis and the key mechanism is controversial. Researches have shown that, as upstream regulatory elements of gene expression, enhancers ar involved in the expression of identity genes. In this study, we identified enhancers-mediated gene FOXO3 promoting MSC adipogenic differentiation by activating autophagy., Methods: We integrated data of RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq) and ATAC-sequencing (ATAC-seq) to find the identity gene FOXO3. The expression of FOXO3 protein, adipogenic transcription factors and the substrate of autophagy were measured by western blotting. The Oil Red O (ORO) staining was used to visualize the adipogenesis of MSCs. Immunohistochemistry was used to visualize the FOXO3 expression in adipocytes in bone marrow. Immunofluorescence was used to detect the expression of PPARγ and LC3B., Results: During adipogenesis, enhancers redistribute to genes associated with adipogenic differentiation, among which we identified the pivotal identity gene FOXO3. FOXO3 could promote the expression of the adipogenic transcription factors PPARγ, CEBPα, and CEBPβ during adipogenic differentiation, while PPARγ, CEBPα, and CEBPβ could in turn bind to FOXO3 and continue to promote FOXO3 expression to form a positive feedback loop. Consistently elevated FOXO3 expression promotes autophagy by activating the PI3K-AKT pathway which mediates adipogenic differentiation., Conclusions: Pivotal identity gene FOXO3 promotes autophagy by activating PI3K-AKT pathway, which provokes adipogenic differentiation of MSCs. Enhancer-regulated adipogenic identity gene FOXO3 could be an attractive treatment for osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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37. Excess feeding increases adipogenesis but lowers leptin transcript abundance in zebrafish larvae.
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Thompson WA, Rajeswari JJ, Holloway AC, and Vijayan MM
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- Animals, Leptin genetics, Leptin metabolism, Larva genetics, PPAR gamma genetics, PPAR gamma metabolism, Lipids, Adipogenesis genetics, Zebrafish metabolism
- Abstract
Although fish exposed to municipal wastewater effluents (MWWE) show higher lipid accumulation, whether this is due to adipogenesis is unclear. The objective here was to identify molecular markers of adipogenesis in zebrafish (Danio rerio) larvae for use as high throughput screening tools for environmental contaminants, including obesogens in MWWE. Zebrafish larvae were fed a commercial diet at a maintenance level (5 % body mass) or in excess (25 or 50 % body mass) from day 6 to 30 days post-fertilization (dpf) to stimulate adipogenesis. We monitored fat accumulation and markers of lipid metabolism, including peroxisome proliferator-activated receptor γ (ppar γ), fatty acid synthase (fas), ELOVL fatty acid elongase 2 (elovl2), diacylglycerol O-acyltransferase 2 (dgat2), leptin (lepa and lepb), leptin receptor (lepr), and lipoprotein lipase (lpl). Excess feeding led to a higher growth rate, protein content and an increase in igf1 transcript abundance. Also, these larvae had higher triglyceride levels and accumulated lipids droplets in the abdominal cavity and viscera. The molecular markers of adipogenesis, including fas, elovl2, and dgat2, were upregulated, while the transcript abundance of lpl, a lipolytic gene, was transiently lower due to excess feeding. The increased adiposity seen at 30 dpf due to excess feeding coincided with a lower lep but not lepr transcript abundance in zebrafish. Our results demonstrate that excess feeding alters the developmental programming of key genes involved in lipid homeostasis, leading to excess lipid accumulation in zebrafish larvae. Overall, fas, elovl2, lpl, and dgat2, but not lep or ppar γ, have the potential to be biomarkers of adipogenesis in zebrafish larvae., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
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38. Mechanobiology of Adipocytes.
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Blade, Sean P., Falkowski, Dylan J., Bachand, Sarah N., Pagano, Steven J., and Chin, LiKang
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FAT cells ,CELLULAR mechanics ,ADIPOGENESIS ,ADIPOSE tissues ,TISSUE mechanics ,ADIPOSE tissue diseases ,CELL physiology - Abstract
Simple Summary: The rising population of people with obesity has presented an important need for the study of how adipocytes (fat cells) behave and affect biological function. Adipocytes have traditionally been thought to only function as energy storage for the body, an assumption that has led to them being understudied in health sciences. However, recent studies have shown that adipocytes experience forces in vivo, are reactive to mechanical stimuli, and their cell function can be altered by changes to the mechanical microenvironment and, in some cases, contribute to disease. The aim of this review is to summarize recent scientific publications on how adipocytes sense and respond to their mechanical environment, the use of engineered scaffolds to study cell behavior, adipose cell and tissue mechanical properties, and the current state of computational models. The growing obesity epidemic necessitates increased research on adipocyte and adipose tissue function and disease mechanisms that progress obesity. Historically, adipocytes were viewed simply as storage for excess energy. However, recent studies have demonstrated that adipocytes play a critical role in whole-body homeostasis, are involved in cell communication, experience forces in vivo, and respond to mechanical stimuli. Changes to the adipocyte mechanical microenvironment can affect function and, in some cases, contribute to disease. The aim of this review is to summarize the current literature on the mechanobiology of adipocytes. We reviewed over 100 papers on how mechanical stress is sensed by the adipocyte, the effects on cell behavior, and the use of cell culture scaffolds, particularly those with tunable stiffness, to study adipocyte behavior, adipose cell and tissue mechanical properties, and computational models. From our review, we conclude that adipocytes are responsive to mechanical stimuli, cell function and adipogenesis can be dictated by the mechanical environment, the measurement of mechanical properties is highly dependent on testing methods, and current modeling practices use many different approaches to recapitulate the complex behavior of adipocytes and adipose tissue. This review is intended to aid future studies by summarizing the current literature on adipocyte mechanobiology. [ABSTRACT FROM AUTHOR]
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- 2024
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39. MicroRNA-378 regulates adipogenic differentiation in bovine intramuscular preadipocytes by targeting
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Dongwei, Li, Heng, Wang, Yongmin, Li, Changqing, Qu, Yunhai, Zhang, Hongyu, Liu, and Xiaorong, Zhang
- Subjects
intramuscular preadipocytes ,Adipogenesis ,bovine ,Cell Differentiation ,Microrna-378 ,PPAR gamma ,MicroRNAs ,Adipocytes ,Animals ,Cattle ,Camkk2 ,adipogenic differentiation ,Research Article ,Research Paper - Abstract
Intramuscular fat, as one of the most important palatability attribute of beef carcase, is the primary determinant of beef quality. The research of adipogenesis mechanism would provide new insight into intramuscular fatty deposition. Here, the role of microRNA-378 was investigated during bovine adipogenic differentiation. It was revealed that miR-378 expression exists variably in bovine major tissue and organs by RT-qPCR. It was predicted that miR-378 targets CaMKK2, as an AMPKα kinase, by DIANA Tools. For better research, primary preadipocytes with stable transfection for up-/down-regulated expression of miR-378 were constructed by lentiviral vectors with GFP gene. The analyses of qPCR showed that PPARγ and adiponectin mRNA levels increased, but C/EBPβ, pref-1 and CaMKK2 mRNA levels decreased during adipogenic differentiation. When miR-378 was overexpressed, preadipocytes proliferation became slower, there are more cellular lipid droplets, and PPARγ and C/EBPβ mRNA levels were higher, but pref-1, adiponectin and CaMKK2 were lower than control groups. Luciferase assay and western blot analysis validated that miR-378 binds the nucleotide sites of the 3′- untranslated region of CaMKK2, which inhibits the mRNA and protein expression of CaMKK2. These findings suggest that miR-378 promotes adipogenic differentiation in bovine intramuscular preadipocytes by targeting CaMKK2 via AMPK signalling pathway.
- Published
- 2021
40. The Effects of Chronological Age on the Chondrogenic Potential of Mesenchymal Stromal Cells: A Systematic Review.
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Vogt, Antonia, Kapetanos, Konstantinos, Christodoulou, Neophytos, Asimakopoulos, Dimitrios, Birch, Mark A., McCaskie, Andrew W., and Khan, Wasim
- Subjects
AGE ,STROMAL cells ,SURFACE analysis ,TISSUE engineering ,REGENERATIVE medicine ,CARTILAGE regeneration ,ADIPOGENESIS - Abstract
Tissue engineering and cell therapy for regenerative medicine have great potential to treat chronic disorders. In musculoskeletal disorders, mesenchymal stromal cells (MSCs) have been identified as a relevant cell type in cell and regenerative strategies due to their multi-lineage potential, although this is likely to be a result of their trophic and immunomodulatory effects on other cells. This PRISMA systematic review aims to assess whether the age of the patient influences the chondrogenic potential of MSCs in regenerative therapy. We identified a total of 3027 studies after performing a search of four databases, including Cochrane, Web of Science, Medline, and PubMed. After applying inclusion and exclusion criteria, a total of 14 papers were identified that were reviewed, assessed, and reported. Cell surface characterization and proliferation, as well as the osteogenic, adipogenic, and chondrogenic differentiation, were investigated as part of the analysis of these studies. Most included studies suggest a clear link between aged donor MSCs and diminished clonogenic and proliferative potential. Our study reveals a heterogeneous and conflicting range of outcomes concerning the chondrogenic, osteogenic, and adipogenic potential of MSCs in relation to age. Further investigations on the in vitro effects of chronological age on the chondrogenic potential of MSCs should follow the outcomes of this systematic review, shedding more light on this complex relationship. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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41. A review of the role of liposome-encapsulated phytochemicals targeting PPAR Ɣ and associated pathways to combat obesity.
- Author
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Shaji, Athira and Jayasri, M. A.
- Subjects
CLINICAL trial registries ,CHILDHOOD obesity ,PEROXISOME proliferator-activated receptors ,PHYTOCHEMICALS ,DRUG utilization ,LIPOSOMES ,OBESITY - Abstract
A limited number of studies have directly examined the effects of liposomal encapsulated phytochemicals and their anti-obesity effects in adults. This study aimed to summarize the evidence on the effect of liposomal encapsulated phytochemicals and their role in regulating major pathways involved in the anti-obesity mechanism. A systematic search was performed using several search engines like Science Direct, Google Scholar, and other online journals, focusing on laboratory research, systematic reviews, clinical trials, and meta-analysis that focused on liposomal encapsulated phytochemicals with anti-obesity properties, and followed the preferred reporting terms for this systematic review. An initial search provided a result of 1810 articles, and 93 papers were selected after the inclusion and exclusion criteria. Very few studies have been conducted on the liposomal encapsulation of phytochemicals or its synergistic study to combat obesity; hence this review paves the way for future obesity research and is mainly helpful for the pediatric obesity population. Liposomal encapsulation of phytochemicals has improved the efficiency of freely administered phytochemicals. Targeted delivery improved drug utilization and regulated the anti-obesity pathways. PPARƔ is a major therapeutic target for obesity as it inhibits adipocyte differentiation and maintains energy homeostasis. [ABSTRACT FROM AUTHOR]
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- 2023
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42. Adipogenic and osteogenic effects of OBS and synergistic action with PFOS via PPARγ-RXRα heterodimers.
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Qin H, Lang Y, Wang Y, Cui W, Niu Y, Luan H, Li M, Zhang H, Li S, Wang C, and Liu W
- Subjects
- Humans, Osteogenesis, PPAR alpha, Molecular Docking Simulation, Adipogenesis, PPAR gamma genetics
- Abstract
Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is a novel alternative to perfluorooctane sulfonate (PFOS), with environmental health risks largely unknown. The present study aims to unravel the adipogenesis effects and underlying molecular initiating events of OBS, which are crucial for understanding and predicting its adverse outcome. In undifferentiated human mesenchymal stem cells (hMSCs), exposure to 1-100 nM of OBS for 7 days stimulated reactive oxygen species production. In the subsequent multipotent differentiation, hMSCs favored adipogenesis and repressed osteogenesis. The point of departure (PoD) for cellular responses of OBS was 38.85 nM, higher than PFOS (0.39 nM). Notably, OBS/PFOS co-exposure inhibited osteogenesis and synergistically promoted adipogenesis. Consistently, the expression of adipogenic marker genes was up-regulated, while that of osteogenic marker genes was down-regulated. The decreased adiponectin and elevated tumor necrosis factor α (TNFα) secretion were observed in differentiated cells exposed to the mixture of OBS and PFOS. The co-treatment of a peroxisome proliferator-activated receptor γ (PPARγ) antagonist alleviated the adipogenic effects of PFOS and its combination with OBS. Moreover, OBS/PFOS co-exposure induced peroxisome PPARγ activation in reporter gene assays, and increased formation of PPARγ - retinoid X receptor α (RXRα) heterodimers measured by co-immunoprecipitation assays. Molecular docking showed interaction energy of OBS (-20.7 kcal/mol) with intact PPARγ-RXRα complex was lower than that of PFOS (-25.9 kcal/mol). Overall, single OBS exhibited lower potency in inducing adipogenesis but is comparable to PFOS in repressing osteogenesis, whereas OBS/PFOS co-exposure increases interaction with PPARγ-RXRα heterodimers, resulting in the synergistic activation of PPARγ, ultimately enhancing adipogenesis at the expense of osteogenic differentiation. The results indicate the potential health risks of increased obesity and decreased bone density caused by OBS and its co-exposure with PFOS, as well as other perfluorinated alkylated substances mixtures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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43. Glucocorticoid signaling and the impact of high-fat diet on adipogenesis in vivo.
- Author
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Babel NK and Feldman BJ
- Subjects
- Humans, Diet, High-Fat adverse effects, Obesity metabolism, Adipocytes metabolism, Adipogenesis, Glucocorticoids metabolism
- Abstract
Our research used glucocorticoids as a medically relevant molecular probe to identify a previously unrecognized ADAMTS1-PTN-Wnt pathway. We elucidated the role of this pathway in regulating adipose precursor cell (APC) behavior to either proliferate or differentiate in response to systemic cues, such as elevated caloric intake. Further, our studies identified the non-muscle myosin protein MYH9 as a key target of this pathway to modulate adipogenesis in vivo. These findings enable strategies toward developing novel therapeutics for obesity and related metabolic disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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44. Phosphodiesterase 4 activity uniquely regulates ciliary cAMP-dependent 3T3-L1 adipogenesis.
- Author
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Erdelsky MR, Groves SA, Shah C, Delios SB, Umana MB, and Maurice DH
- Subjects
- Mice, Animals, 3T3-L1 Cells, Cell Differentiation, Docosahexaenoic Acids, PPAR gamma, Adipogenesis, Cyclic Nucleotide Phosphodiesterases, Type 4
- Abstract
Recent evidence indicates that the presence of a primary cilium (PC), and of selective cAMP signaling within this smallest of organelles, promotes adipogenic differentiation of 3T3-L1 preadipocytes incubated in media supplemented with either a natural (docosahexaenoic acid, DHA), or a synthetic (TUG-891), free fatty acid receptor 4 (FFAR4) agonist. Indeed, in this earlier work, activation of ciliary FFAR4 in 3T3-L1 cells was correlated with selective increases in PC cAMP and adipogenesis in these cells. However, this study was silent on the role of local PC cAMP phosphodiesterases (PDEs)-mediated events in regulating these adipogenic responses and on the identity of cAMP PDEs that could regulate the "pool" of ciliary cAMP accessed by FFAR4 agonists. In this context, we have identified the PDEs expressed by 3T3-L1 preadipocytes and showed that of these, only PDE4 inhibition promotes FFAR4-mediated adipogenesis. We propose that this work will identify more selective therapeutic targets through which to control adipogenesis, and perhaps the differentiation of other stem cells in which ciliary cAMP is critical., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Donald Maurice reports financial support was provided by Canadian Institutes of Health Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
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45. Anti-adipogenic action of a novel oxazole derivative through activation of AMPK pathway.
- Author
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Mishra T, Gupta S, Rai P, Khandelwal N, Chourasiya M, Kushwaha V, Singh A, Varshney S, Gaikwad AN, and Narender T
- Subjects
- Cricetinae, Animals, Humans, Mice, AMP-Activated Protein Kinases metabolism, Mesocricetus, Adipocytes metabolism, Obesity drug therapy, Obesity metabolism, 3T3-L1 Cells, Adipogenesis, Dyslipidemias
- Abstract
Obesity is a chronic disorder with multifactorial etiology, including genetic, medical, dietary and other environmental factors. Both natural and synthetic heterocyclic compounds, especially oxazoles, represent an interesting group of compounds and have gained much attention due to their remarkable biological activities. Therefore, a library of 3,3-DMAH (3,3-dimethylallylhalfordinol) inspired N-alkylated oxazole bromide salts with varied substitutions were prepared and screened using the 3T3-L1 model of adipogenesis and HFD-induced obesity model in Syrian golden hamsters. Several compounds in the synthesized series displayed remarkable anti-adipogenic potential on the differentiation of 3T3-L1 preadipocytes. Compound 19e, displayed the most potent activity of all and selected for further studies. Compound 19e inhibited mitotic clonal expansion of 3T3-L1 cells and enhanced the mitochondrial oxygen consumption rate of the cells during early phase of differentiation via AMPK activation. 19e also improved the dyslipidaemia in high calorie diet fed Syrian Golden Hamsters. Therefore, compound 19e can serve as a potential lead against adipogenesis and dyslipidaemia models and could be further investigated to affirm its significance as a drug candidate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)
- Published
- 2023
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46. Vitisin A-13-O-β-D-glucoside and Vitisin A from Iris lactea inhibit lipogenesis and promote lipolysis via the PKA/HSL pathway during adipogenic transdifferentiation of C2C12 cells.
- Author
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Tie F, Hu N, Dong Q, and Wang H
- Subjects
- Mice, Animals, Lipolysis, Lipogenesis, Sterol Esterase metabolism, Glucosides pharmacology, Cell Transdifferentiation, Lipids, 3T3-L1 Cells, PPAR gamma metabolism, Adipogenesis, Iris Plant metabolism
- Abstract
Oligostilbenes are a group of natural products derived from the polymerization of stilbene monomers. Despite the demonstration of their activities in regulating lipid metabolism, the function of oligostilbenes in the adipogenic transdifferentiation of multipotent myoblast cells remains unknown. Hence, the five oligostilbenes from Iris lactea were tested for their regulatory effects on adipogenic transdifferentiation of C2C12 myoblast cells. As a result, it was shown that Vitisin A-13-O-β-D-glucoside (VitAOG), Vitisin A (VitA) and Hopeaphenol (Hop) can greatly inhibit the adipogenic transdifferentiation of C2C12 cells by reducing lipid accumulation and downregulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein beta (C/EBPβ) and fatty acid binding proteins 4 (FABP4). In contrast, Vitisin D (VitD) and Isohopeaphenol (Isohop) promote adipogenic transdifferentiation of C2C12 cells by increasing lipid accumulation and upregulating the expression of adipogenesis and lipogenesis markers. Further research found that the lipolytic protein levels of adipocyte triglyceride lipase (ATGL) and phosphorylation of hormone-sensitive lipase (HSL) were elevated by VitAOG and VitA. Additionally, VitAOG and VitA maintain lipid homeostasis by improving mitochondrial function. Taken together, our study reveals an effect of oligostilbenes on lipid metabolism in C2C12 cells, and VitAOG and VitA can be regarded as potential candidates for the treatment of obesity and other disorders of lipid metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2023
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47. Research progress of intramuscular fat formation based on co-culture.
- Author
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Song Y, Wei D, Raza SHA, Zhao Y, Jiang C, Song X, Wu H, Wang X, Luoreng Z, and Ma Y
- Subjects
- Humans, Animals, Coculture Techniques, Cell Differentiation, Meat, Muscle, Skeletal physiology, Adipose Tissue physiology, Adipogenesis, Adipocytes physiology
- Abstract
Intramuscular fat (IMF) is closely related to the meat quality of livestock and poultry. As a new cell culture technique in vitro , cell co-culture has been gradually applied to the related research of IMF formation because it can simulate the changes of microenvironment in vivo during the process of IMF cell formation. In the co-culture model, in addition to studying the effects of skeletal muscle cells on the proliferation and differentiation of IMF, we can also consider the role of many secretion factors in the formation of IMF, thus making the cell research in vitro closer to the real level in vivo . This paper reviewed the generation and origin of IMF, summarized the existing co-culture methods and systems, and discussed the advantages and disadvantages of each method as well as the challenges faced in the establishment of the system, with emphasis on the current status of research on the formation of IMF for human and animal based on co-culture technology.
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- 2023
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48. lpla (lipoprotein lipase a) is a marker of early adipogenesis rather than late adipogenesis in grass carp (Ctenopharyngodon idellus).
- Author
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Tian Z, Wei M, Xue R, Song L, Li H, Ji H, and Sun J
- Subjects
- Animals, Lipoprotein Lipase genetics, RNA, Messenger metabolism, Amino Acids, Fish Proteins metabolism, Mammals genetics, Mammals metabolism, Adipogenesis, Carps genetics, Carps metabolism
- Abstract
Lipoprotein lipase (LPL) functions as a marker of adipocyte differentiation in mammals, but little is known about its role in fish adipogenesis. The aim of this research is to investigate the function of Lpl in adipocyte differentiation in fish. In this paper, we isolated and characterized lipoprotein lipase a (lpla) and lipoprotein lipase b (lplb) from grass carp (Ctenopharyngodon idellus). The complete coding sequence of lpla and lplb was 1524 bp and 1503 bp in length, coding for 507 amino acids and 500 amino acids, respectively. Both lpla and lplb mRNA were expressed in a great number of tissues. During adipogenesis, the level of lpla mRNA reached its maximum at day 2 and then dropped gradually, while the level of lplb mRNA had no significant changes, indicating that lpla and lplb may have different function in the differentiation of grass carp adipocyte. Furthermore, inhibition of lpla by inhibitor of LPL(GSK264220A) at early time points most clearly reduced adipogenesis, whereas these effects were less pronounced at later stages, suggesting that lpla predominantly affects early adipogenesis rather than late adipogenesis. Based on these findings, it can be inferred that lpla and lplb in grass carp may have distinct roles in the differentiation of grass carp adipocyte, and lpla may play an important role in the early adipogenesis rather than late adipogenesis in grass carp., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)
- Published
- 2023
- Full Text
- View/download PDF
49. Identification of a Novel Long Non-Coding RNA G8110 That Modulates Porcine Adipogenic Differentiation and Inflammatory Responses.
- Author
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Chai J, Wang N, Chen L, Bai J, Zhang J, Zhang G, An J, Zhang T, Tong X, Wu Y, Li M, and Jin L
- Subjects
- Animals, Swine, Adipocytes metabolism, Cell Differentiation genetics, Lipids, Adipogenesis genetics, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism
- Abstract
Long non-coding RNAs (lncRNAs) have been extensively studied, and their crucial roles in adipogenesis, lipid metabolism, and gene expression have been revealed. However, the exact regulatory or other mechanisms by which lncRNAs influence the functioning of mesenteric adipose tissue (MAT) remain largely unknown. In this paper, we report the identification of a new lncRNA, named G8110, from the MAT of Bama pigs. The coordinated expression levels of lncRNA G8110 and NFE2L1 were significantly decreased in the MAT of obese Bama pigs compared with those in the MAT of lean pigs. Using a bone mesenchymal stem cell adipogenic differentiation model, we found that lncRNA G8110 played a role in adipocyte differentiation by positively regulating NFE2L1 . We also found that lncRNA G8110 inhibited the formation of intracellular lipid synthesis, promoted lipid metabolism, and inhibited the expression of inflammatory cytokines. Our findings regarding lipid synthesis may further promote the role of lncRNAs in driving adipose tissue remodeling and maintaining metabolic health.
- Published
- 2023
- Full Text
- View/download PDF
50. Dual mechanism of silver nanoparticle-mediated upregulation of adipogenesis in mouse fibroblasts (3T3-L1) in vitro.
- Author
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Skóra B, Piechowiak T, and Szychowski KA
- Subjects
- Animals, Mice, Up-Regulation, Silver toxicity, Silver metabolism, PPAR gamma genetics, PPAR gamma metabolism, 3T3-L1 Cells, Reactive Oxygen Species metabolism, Cell Differentiation, Lipids, Adipogenesis genetics, Metal Nanoparticles toxicity
- Abstract
Silver nanoparticles (AgNPs) are widespread in the environment due to the increase in their application e.g. in medicine as part of hard-to-heal wound dressings. Many studies have revealed easy diffusion of AgNPs into deep skin layers through damaged epidermis and contact with e.g. fibroblasts. Therefore, the aim of this study was to evaluate the impact of small-size AgNPs (10 nm) in ppm concentrations on the adipogenesis process in mouse embryo fibroblasts (3T3-L1). The results showed a decrease in the metabolic activity, followed by an increase in the reactive oxygen species (ROS) level in a dose- and time-dependent manner (0-20 ppm). The increased caspase-3 activity was observed only at the highest concentration (20 ppm) of AgNPs. Further analysis showed the ability of the tested NPs to increase the lipid accumulation in adipocytes, similar to ROSI [peroxisome proliferator-activated receptor gamma (PPARγ) agonist], measured by Oil-Red-O staining. Moreover, the analyses evidenced the ability of AgNPs to increase the lipoxygenase activity and malondialdehyde levels, which is probably based on ROS-dependent enhancement of lipid hydroperoxidation. Lastly, a significant increase in the PPARγ, Adiponectin, Resistin, Vegf, and Serpine mRNA expression was shown 6 h after the induction of the differentiation process. Based on the obtained results, it can be concluded that small-size AgNPs increase adipogenesis via ROS- and PPARγ-based mechanisms with potential engagement of crosstalk with the aryl hydrocarbon receptor, which is important due to the widespread application of AgNPs in medicine. However, more studies are needed to elucidate the full mechanism of these NPs in the tested cell model in depth., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
- Full Text
- View/download PDF
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