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Previous studies have shown that subcutaneous adipose tissue is an important energy supply organ for chicks before and after birth, except yolk. So far, the significance of large deposits of subcutaneous adipose tissue in chicks is unclear. Therefore, this study takes the information interaction between adipocytes and macrophages as the starting point to explore whether adipocytes and macrophages could participate in adipose tissue fibrosis, angiogenesis, adaptive thermogenesis and other related functions in a specific metabolic environment. Under cold stress, the expression levels of genes related to lipidolysis, lipid transport and fatty acid oxidation in adipose tissue of chicks were significantly increased, but the expression levels of genes related to mitochondrial uncoupling were not significantly changed. Through Masson staining of adipose tissue of chicks under cold stress, it was found that the level of vascularization in adipose tissue of chicks was significantly increased. We found that the interaction between adipocyte and macrophage could participate in the angiogenesis related process of adipocytes in chicks through the HIF1A-VEGFA pathway. The analysis of lipid metabolism in subcutaneous adipose tissue of chicks from the perspective of cell heterogeneity will expand the understanding of lipid metabolism in chicks and provide a theoretical basis for chick rearing.

Bone development and bone remodelling during adult life are highly anabolic processes requiring an adequate supply of oxygen and nutrients. Bone-forming osteoblasts and bone-resorbing osteoclasts interact closely to preserve bone mass and architecture and are often located close to blood vessels. Chondrocytes within the developing growth plate ensure that bone lengthening occurs before puberty, but these cells function in an avascular environment. With ageing, numerous bone marrow adipocytes appear, often with negative effects on bone properties. Many studies have now indicated that skeletal cells have specific metabolic profiles that correspond to the nutritional microenvironment and their stage-specific functions. These metabolic networks provide not only skeletal cells with sufficient energy, but also biosynthetic intermediates that are necessary for proliferation and extracellular matrix synthesis. Moreover, these metabolic pathways control redox homeostasis to avoid oxidative stress and safeguard cell survival. Finally, several intracellular metabolites regulate the activity of epigenetic enzymes and thus control the fate and function of skeletal cells. The metabolic profile of skeletal cells therefore not only reflects their cellular state, but can also drive cellular activity. Insight into skeletal cell metabolism will thus not only advance our understanding of skeletal development and homeostasis, but also of skeletal disorders, such as osteoarthritis, diabetic bone disease and bone malignancies., (© 2024. Springer Nature Limited.)

Bone marrow adipose tissue (BMAT) is a metabolically and clinically relevant fat depot that exists within bone. Two subtypes of BMAT, regulated and constitutive, reside in hematopoietic-rich red marrow and fatty yellow marrow, respectively, and exhibit distinct characteristics compared to peripheral fat such as white and brown adipose tissues. Bone marrow adipocytes (BMAds) are evolutionally preserved in most vertebrates, start development after birth and expand throughout life, and originate from unique progenitor populations that control bone formation and hematopoiesis. Mature BMAds also interact closely with other cellular components of the bone marrow niche, serving as a nearby energy reservoir to support the skeletal system, a signaling hub that contributes to both local and systemic homeostasis, and a final fuel reserve for survival during starvation. Though BMAT and bone are often inversely correlated, more BMAT does not always mean less bone, and the prevention of BMAT expansion as a strategy to prevent bone loss remains questionable. BMAT adipogenesis and lipid metabolism are regulated by the nervous systems and a variety of circulating hormones. This contributes to the plasticity of BMAT, including BMAT expansion in common physiological or pathological conditions, and BMAT catabolism under certain extreme circumstances, which are often associated with malnutrition and/or systemic inflammation. Altogether, this article provides a comprehensive overview of the local and systemic functions of BMAT and discusses the regulation and plasticity of this unique adipose tissue depot in health and disease. © 2024 American Physiological Society. Compr Physiol 14:5521-5579, 2024., (Copyright © 2024 American Physiological Society. All rights reserved.)

Adipose tissue is highly plastic, as illustrated mainly by the transdifferentiation of white adipocytes into beige adipocytes, depending on environmental conditions. However, during gestation and lactation in rodent, there is an amazing phenomenon of transformation of subcutaneous adipose tissue into mammary glandular tissue, known as pink adipose tissue, capable of synthesizing and secreting milk. Recent work using transgenic lineage-tracing experiments, mainly carried out in Saverio Cinti's team, has demonstrated very convincingly that this process does indeed correspond to a transdifferentiation of white adipocytes into mammary alveolar cells (pink adipocytes) during gestation and lactation. This phenomenon is reversible, since during the post-lactation phase, pink adipocytes revert to the white adipocyte phenotype. The molecular mechanisms underlying this reversible transdifferentiation remain poorly understood., (Copyright © 2024. Published by Elsevier Masson SAS.)

E2F transcription factor 5 (E2F5) gene is a transcription factor, plays an important role in the development of a variety of cells. E2F5 is expressed in human and mouse adipocytes, but its specific function in adipogenesis is unclear. Krüppel-like factor 7 (KLF7) facilitates proliferation and inhibits differentiation in chicken preadipocytes. Our previous KLF7 chromatin immunoprecipitation-sequencing analysis revealed a KLF7-binding peak in the 3' flanking region of the E2F5, indicating a regulatory role of KLF7 in this region. In the present study, we investigated E2F5 potential role, the overexpression and knockdown analyses revealed that E2F5 inhibited the differentiation and promoted the proliferation of chicken preadipocytes. Moreover, we identified enhancer activity in the 3' flanking region (nucleotides +22661/+22900) of E2F5 and found that KLF7 overexpression increased E2F5 expression and luciferase activity in this region. Deleting the putative KLF7-binding site eliminated the promoting effect of KLF7 overexpression on E2F5 expression. Further, E2F5 reversed the KLF7-induced decrease in preadipocyte differentiation and increase in preadipocyte proliferation. Taken together, our findings demonstrate that KLF7 inhibits differentiation and promotes proliferation in preadipocytes by enhancing E2F5 transcription., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We studied the interaction of human buccal mesenchymal stem cells (MSCs) and osteoblasts differentiated from them with the surface of titanium samples. MSCs were isolated by enzymatic method from buccal fat pads. The obtained cell culture was presented by MSCs, which was confirmed by flow cytometry and differentiation into adipocytes and osteoblasts. Culturing of buccal MSCs on titanium samples was accompanied by an increase in the number of cells for 15 days and the formation of a developed network of F-actin fibers in the cells. The viability of buccal MSCs decreased by 8 days, but was restored by 15 days. Culturing of osteoblasts obtained as a result of buccal MSC differentiation on the surface of titanium samples was accompanied by a decrease in their viability and proliferation. Thus, MSCs from buccal fat pads can be used to coat implants to improve osseointegration during bone reconstruction in craniofacial surgery and dentistry. To improve the integration of osteoblasts, modification of the surface of titanium samples is required., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Radiation-induced fibrosis is a recognised consequence of radiotherapy, especially after multiple and prolonged dosing regimens. There is no definitive treatment for late-stage radiation-induced fibrosis, although the use of autologous fat transfer has shown promise. However, the exact mechanisms by which this improves radiation-induced fibrosis remain poorly understood. We aim to explore existing literature on the effects of autologous fat transfer on both in-vitro and in-vivo radiation-induced fibrosis models, and to collate potential mechanisms of action., Method: PubMed, Cochrane reviews and Scopus electronic databases from inception to May 2023 were searched. Our search strategy combined both free-text terms with Boolean operators, derived from synonyms of adipose tissue and radiation-induced fibrosis., Results: The search strategy produced 2909 articles. Of these, 90 underwent full-text review for eligibility, yielding 31 for final analysis. Nine conducted in-vitro experiments utilising a co-culture model, whilst 25 conducted in-vivo experiments. Interventions under autologous fat transfer included adipose-derived stem cells, stromal vascular function, whole fat and microfat. Notable findings include downregulation of fibroblast proliferation, collagen deposition, epithelial cell apoptosis, and proinflammatory processes. Autologous fat transfer suppressed hypoxia and pro-inflammatory interferon-γ signalling pathways, and tissue treated with adipose-derived stem cells stained strongly for anti-inflammatory M2 macrophages. Although largely proangiogenic initially, studies show varying effects on vascularisation. There is early evidence that adipose-derived stem cell subgroups may have different functional properties., Conclusion: Autologous fat transfer functions through pro-angiogenic, anti-fibrotic, immunomodulatory, and extracellular matrix remodelling properties. By characterising these mechanisms, relevant drug targets can be identified and used to further improve clinical outcomes in radiation-induced fibrosis. Further research should focus on adipose-derived stem cell sub-populations and augmentation techniques such as cell-assisted lipotransfer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pattani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As a member of the PGAMs family, PGAM2 has been proved to catalyze the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. However, it is unclear whether PGAM2 has a role in regulating differentiation in goat intramuscular preadipocytes. Here, this study was carried to clone the open reading frame (ORF) of goat PGAM2 , elucidate its molecular and expressional characteristics, and evaluate the involvement in adipogenesis of intramuscular preadipocytes. According to our findings, the cloned goat PGAM2 gene was 784 bp in full length, including 762 bp of ORF and encoding a protein of 253 amino acids. The expressional level of PGAM2 peaked at 48 hours after induced adipogenic differentiation and was highest in the skeletal muscle of triceps. Moreover, overexpression of PGAM2 transfected by its overexpression plasmid promotes lipid accumulation of goat intramuscular adipocyte as shown by Oil Red O and bodipy staining, accompanied by up-regulating the mRNA levels of peroxisome proliferator-activated receptor γ ( PPARγ ) ( p  < 0.001), sterol regulatory element-binding protein 1 ( SREBP1 ) ( p  < 0.001), CCAAT/Enhancer-binding protein α ( C/EBPα ) ( p  < 0.01) and lipoprotein lipase ( LPL ) ( p  < 0.01). Taken together, these findings indicate that PGAM2 is a positive regulator for goat intramuscular adipocytes and provide new insights into improvement intramuscular fat deposition in goat meat.

Intramuscular fat (IMF) content is one of the most significant factors influencing beef quality in terms of tenderness, flavor, and juiciness. Thus, internal factors affecting IMF deposition have received considerable attention for decades. In this study, we demonstrated a long non-coding RNA, lnc210, promoted adipogenic differentiation of buffalo intramuscular adipocytes. lnc210 was rich in adipose tissue and showed increased expression with the adipogenic differentiation of buffalo intramuscular adipocytes. lnc210 was mainly expressed in the nucleus of adipocytes. Full-length lnc210 was obtained by rapid amplification of cDNA ends technology. lnc210 overexpression promoted lipid accumulation by upregulating the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) and CCAAT enhancer binding protein alpha (C/EBPα) in buffalo intramuscular adipocytes. These results provide a basis for an in-depth analysis of the role of lnc210 in accelerating IMF deposition in buffaloes.

Intramuscular fat (IMF) positively influences various aspects of meat quality, while the subcutaneous fat (SF) has negative effect on carcass characteristics and fattening efficiency. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation, herein, through bioinformatic screen for the potential regulators of adipogenesis from two independent microarray datasets, we identified that PPARγ is a potentially regulator between porcine IMF and SF adipogenesis. Then we treated subcutaneous preadipocytes (SA) and intramuscular preadipocytes (IMA) of pig with RSG (1 µmol/L), and we found that RSG treatment promoted the differentiation of IMA via differentially activating PPARγ transcriptional activity. Besides, RSG treatment promoted apoptosis and lipolysis of SA. Meanwhile, by the treatment of conditioned medium, we excluded the possibility of indirect regulation of RSG from myocyte to adipocyte and proposed that AMPK may mediate the RSG-induced differential activation of PPARγ. Collectively, the RSG treatment promotes IMA adipogenesis, and advances SA lipolysis, this effect may be associated with AMPK-mediated PPARγ differential activation. Our data indicates that targeting PPARγ might be an effective strategy to promote intramuscular fat deposition while reduce subcutaneous fat mass of pig.

TEA domain transcription factor 1 ( TEAD1 ), also called TEF-1 , acts as a transcriptional enhancer to regulate muscle-specific gene expression. However, the role of TEAD1 in regulating intramuscular preadipocyte differentiation in goats is unclear. The aim of this study was to obtain the sequence of TEAD1 gene and elucidate the effect of TEAD1 on goat intramuscular preadipocyte differentiation in vitro and its possible mechanism. The results showed that the goat TEAD1 gene CDS region sequence was 1311 bp. TEAD1 gene was widely expressed in goat tissues, with the highest expression in brachial triceps ( p  < 0.01). The expression of TEAD1 gene in goat intramuscular adipocytes at 72 h was extremely significantly higher than that at 0 h ( p  < 0.01). Overexpression of goat TEAD1 inhibited the accumulation of lipid droplets in goat intramuscular adipocyte. The relative expression of differentiation marker genes SREBP1 , PPARγ , C/EBPβ were significantly down-regulated (all p  < 0.01), but PREF-1 was significantly up-regulated ( p  < 0.01). Binding analysis showed that there were multiple binding sites between the DNA binding domain of goat TEAD1 and the promoter binding region of SREBP1 , PPARγ , C/EBPβ and PREF-1 . In conclusion, TEAD1 negatively regulates the differentiation of goat intramuscular preadipocytes.

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.

Fibroblast growth factor 1( FGF 1) has been proved to bind to specific signal molecules and activate intracellular signal transduction, leading to proliferation or differentiation of cells. However, the role of FGF 1 in goat adipocytes is still unclear. Here, we investigated its role in lipogenesis of goats, which depends on the activation of FGFRs. In goat intramuscular and subcutaneous adipocytes, we observed that adipocytes accumulation was inhibited by interfering of FGF 1, the expression of C / EBP α, C / EBP β, LPL , Pref -1, PPAR γ, AP 2, KLF 4, KLF 6, KLF 10 and KLF 17 were significantly down-regulated ( p  < 0.05). When the FGF 1 was up-regulated, the opposite result was found, while the expression of C / EBP β, LPL , PPAR γ, SREBP 1, AP 2, KLF 4, KLF 7, KLF 15, KLF 16 and KLF 17 were increased significantly ( p  < 0.05) in goat intramuscular and subcutaneous adipocytes. The expression level of FGFR 1 was significantly and decreased with the interference of FGF 1, and increased with the overexpression of FGF 1. But in goat subcutaneous adipocytes, only the expression of FGFR 2 was consistent with the expression of FGF 1. Interference methods confirmed that FGFR 1 or FGFR 2 and FGF 1 have the similarly promoting function in adipocytes differentiation. With the co-transfection technology, we confirmed that FGF 1 promoted the differentiation of intramuscular and subcutaneous adipocytes might via FGFR 1 or FGFR 2, respectively.

Background: Lipedema, diagnosed most often in women, is a progressive disease characterized by the disproportionate and symmetrical distribution of adipose tissue, primarily in the extremities. Although numerous results from in vitro and in vivo studies have been published, many questions regarding the pathology and genetic background of lipedema remain unanswered., Methods: In this study, adipose tissue-derived stromal/stem cells were isolated from lipoaspirates derived from nonobese and obese donors with or without lipedema. Growth and morphology, metabolic activity, differentiation potential, and gene expression were evaluated using quantification of lipid accumulation, metabolic activity assay, live-cell imaging, reverse transcription polymerase chain reaction, quantitative polymerase chain reaction, and immunocytochemical staining., Results: The adipogenic potential of lipedema and nonlipedema adipose tissue-derived stromal/stem cells did not rise in parallel with the donors' body mass index and did not differ significantly between groups. However, in vitro differentiated adipocytes from nonobese lipedema donors showed significant upregulation of adipogenic gene expression compared with nonobese controls. All other genes tested were expressed equally in lipedema and nonlipedema adipocytes. The adiponectin/leptin ratio was significantly reduced in adipocytes from obese lipedema donors compared with their nonobese lipedema counterparts. Increased stress fiber-integrated smooth muscle actin was visible in lipedema adipocytes compared with nonlipedema controls and appeared enhanced in adipocytes from obese lipedema donors., Conclusions: Not only lipedema per se but also body mass index of donors affect adipogenic gene expression substantially in vitro. The significantly reduced adiponectin/leptin ratio and the increased occurrence of myofibroblast-like cells in obese lipedema adipocyte cultures underscores the importance of attention to the co-occurrence of lipedema and obesity. These are important findings toward accurate diagnosis of lipedema., Clinical Relevance Statement: Our study highlights not only the difficulty in lipedema diagnostics but also the tremendous need for further studies on lipedema tissue. Although lipedema might seem to be an underestimated field in plastic and reconstructive surgery, the power it holds to provide better treatment to future patients can not be promoted enough., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis, as well as potentially nourishing the bone marrow during periods of stress. Bone marrow adipose tissue is regulated by multiple factors, but particularly nutrient status. In this Review, we examine how bone marrow adipocytes originate, their function in normal and pathological states and how bone marrow adipose tissue modulates whole-body homoeostasis through actions on bone cells, haematopoietic stem cells and extra-medullary adipocytes during nutritional challenges. We focus on both rodent models and human studies to help understand the unique marrow adipocyte, its response to the external nutrient environment and its effects on the skeleton. We finish by addressing some critical questions that to date remain unanswered., (© 2023. Springer Nature Limited.)

Recently, emerging evidence has shown that LncRNA MEG3 is involved in adipocyte inflammation and insulin resistance progression, however, the specific mechanism of action remains unclear. In this study, we found that LncRNA MEG3 expression was increased in TNF-α stimulated 3T3-L1 mature adipocytes, and inflammatory factors IL-6 and MCP-1 secretion levels were increased, cell apoptosis and caspase3 activity was enhanced, ROS content was increased, and iNOS protein expression was increased. Moreover, TNF-α treatment attenuated glucose uptake, promoted triglyceride accumulation, inhibited GLUT4 protein expression at the plasma membrane, and reduced the phosphorylation levels of AMPK and ACC in the cells. Interestingly, we found that transfection of si-MEG3 reversed TNF-α caused inflammatory injury and insulin resistance of 3T3-L1 mature adipocytes. Next, we found that IGF2BP2 is an RNA binding protein of LncRNA MGE3 and transfection of si-IGF2BP2 reversed TNF-α caused inflammatory injury and insulin resistance in 3T3-L1 mature adipocytes, the same effects as transfection of si-MEG3. Mechanistically, LncRNA MGE3 was able to aggravate adipocyte inflammatory injury and dysregulation of insulin sensitivity by activating TLR4 pathway through upregulating the protein expression of IGF2BP2. In vivo findings showed that HFD mice with knockdown of MEG3 had reduced body weight, lower glucose concentrations and insulin levels in plasma, decreased inflammatory factors secretion, and reduced MEG3 and IGF2BP2 expression in epididymal adipose tissues and reduced fat accumulation in mice compared with HFD mice. Our results indicate that LncRNA MEG3 can aggravate chronic inflammation and insulin resistance in adipocytes by activating TLR4/NF-κB signaling pathway via targeting IGF2BP2., 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.)

Background: The pathophysiology of adipose proliferation or differentiation in extremity lymphedema has not been thoroughly studied. This study investigated the impacts of the lymph harvested from lymphedematous limbs on the adipogenesis of adipose-derived stem cells (ASCs)., Methods: ASCs were isolated from the adipose tissue of normal extremities and cultured with lymph collected from Cheng lymphedema grade III to IV patients or adipogenic differentiation medium (ADM) and further subjected to differentiation and proliferation assay. The expression of adipogenesis genes was examined by real-time polymerase chain reaction to investigate the effect of lymph on ASCs. The level of adipogenic cytokines in the lymph was also evaluated., Results: The adipocytes were significantly larger in lymphedema fat tissue compared with that in normal fat tissues ( P < 0.00). The adipogenesis of ASCs cultured in lymph was significantly enhanced compared with in ADM ( P = 0.008) on day 10, suggesting that the adipogenesis of ASCs was promoted under the lymph-cultured environment. The expression of adipogenesis genes, peroxisome proliferator-activated receptor ( P = 0.02), CAAT/enhancer-binding protein α ( P = 0.008); fatty-acid binding protein ( P = 0.004), and lipoprotein lipase ( P = 0.003), was statistically elevated when the ASCs were cultured with lymph. The insulin content in lymph was statistically higher in lymph ( P < 0.001) than in plasma., Conclusions: The adipogenesis of ASCs was promoted under the lymph-cultured environment with statistically increased adipogenesis genes of peroxisome proliferator-activated receptor, CAAT/enhancer-binding protein α, fatty-acid binding protein, and lipoprotein lipase. The excess lymph accumulated in the lymphedematous extremity contained a greater insulin/insulin-like growth factor-2. These adipogenic factors promoted the expression of early adipogenesis genes and led ASCs to undergo adipogenesis and differentiated into adipocytes., Clinical Relevance Statement: The accumulation of adipose tissue in the lymphedema region was contributed from the content of excess lymph., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Intramuscular fat is positively related to meat quality including tenderness, flavor, and juiciness. Long noncoding RNA (LncRNA) plays a vital role in regulating adipogenesis. However, it is largely unknown about lncRNAs associated with porcine intramuscular adipocyte adipogenesis. In the present study, we focus on a novel LncRNA, which is named lncIMF2, associated with adipogenesis by our previous RNA-sequence analysis and bioinformatics analysis. We demonstrated LncIMF2 knockdown inhibited the proliferation of porcine intramuscular adipocytes while expression of cell cycle-related genes was decreased. Besides, we found LncIMF2 knockdown inhibited expression of adipogenic differentiation marker genes including PPARγ (Peroxisome proliferator-activated reporter gamma) and ATGL (Adipose triglyceride lipase). Similarly, overexpression of LncIMF2 promotes proliferation and differentiation of porcine intramuscular preadipocytes. Moreover, we proved that IncIMF2 acts as a molecular sponge for MicroRNA-217 (miR-217), which has been found associated with adipogenesis, thereby affecting the expression of the miR-217 target gene. Collectively, our findings will contribute to a deeper understanding of the role of LncRNA in pig IMF deposition for the improvement of meat quality.

Although the adipose tissue (AT) is a central metabolic organ in the regulation of whole-body energy homeostasis, it is also an important endocrine and immunological organ. As an endocrine organ, AT secretes a variety of bioactive peptides known as adipokines - some of which have inflammatory and immunoregulatory properties. As an immunological organ, AT contains a broad spectrum of innate and adaptive immune cells that have mostly been studied in the context of obesity. However, overwhelming evidence supports the notion that AT is a genuine immunological effector site, which contains all cell subsets required to induce and generate specific and effective immune responses against pathogens. Indeed, AT was reported to be an immune reservoir in the host's response to infection, and a site of parasitic, bacterial and viral infections. In addition, besides AT's immune cells, preadipocytes and adipocytes were shown to express innate immune receptors, and adipocytes were reported as antigen-presenting cells to regulate T-cell-mediated adaptive immunity. Here we review the current knowledge on the role of AT and AT's immune system in host defense against pathogens. First, we will summarize the main characteristics of AT: type, distribution, function, and extraordinary plasticity. Second, we will describe the intimate contact AT has with lymph nodes and vessels, and AT immune cell composition. Finally, we will present a comprehensive and up-to-date overview of the current research on the contribution of AT to host defense against pathogens, including the respiratory viruses influenza and SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barthelemy, Bogard and Wolowczuk.)

Obesity treatment is a global public health challenge due to inadequate weight loss and weight regain even after endeavors with multimodal treatments. Considering the abundance of resident macrophages in adipose tissues, precise regulation of the interactions between macrophages and adipocytes may provide chances for immunotherapy of obesity. Herein, inspired by the phagocytosis of macrophages to clear apoptotic cells in homeostasis, an immunotherapy strategy for obesity treatment is proposed for the first time through apoptotic camouflage of adipocytes by PA Au BPs to activate macrophages for clearance, where PA Au BPs are gold nanobipyramids engineered with adipose-targeting and apoptotic cell-mimicking functions. During clearance, the macrophage is switched from pro-inflammatory M1 to anti-inflammatory M2, remarkably modulating the immune microenvironment of adipose tissues to prevent weight regain. After inguinal injection with PA Au BPs, the body weights of obese mice are effectively decreased by 24.4% and can be decreased by 33.3% when combined with photothermal lipolysis, and little weight regain is associated with these treatments. This study demonstrates that the strategy of camouflaging adipocytes with apoptotic features holds great potential for obesity immunotherapy., (© 2022 Wiley-VCH GmbH.)

Childhood obesity is a serious public health crisis and a critical factor that determines future obesity prevalence. Signals affecting adipocyte development in early postnatal life have a strong potential to trigger childhood obesity; however, these signals are still poorly understood. We show here that mitochondrial (mt)RNA efflux stimulates transcription of nuclear-encoded genes for mitobiogenesis and thermogenesis in adipocytes of young mice and human infants. While cytosolic mtRNA is a potential trigger of the interferon (IFN) response, young adipocytes lack such a response to cytosolic mtRNA due to the suppression of IFN regulatory factor (IRF)7 expression by vitamin D receptor signalling. Adult and obese adipocytes, however, strongly express IRF7 and mount an IFN response to cytosolic mtRNA. In turn, suppressing IRF7 expression in adult adipocytes restores mtRNA-induced mitobiogenesis and thermogenesis and eventually mitigates obesity. Retrograde mitochondrion-to-nucleus signalling by mtRNA is thus a mechanism to evoke thermogenic potential during early adipocyte development and to protect against obesity., (© 2022. The Author(s).)

Most mammalian cells have an intrinsic circadian clock that coordinates metabolic activity with the daily rest and wake cycle. The circadian clock is known to regulate cell differentiation, but how continuous daily oscillations of the internal clock can control a much longer, multiday differentiation process is not known. Here, we simultaneously monitor circadian clock and adipocyte-differentiation progression live in single cells. Strikingly, we find a bursting behavior in the cell population whereby individual preadipocytes commit to differentiate primarily during a 12-h window each day, corresponding to the time of rest. Daily gating occurs because cells irreversibly commit to differentiate within only a few hours, which is much faster than the rest phase and the overall multiday differentiation process. The daily bursts in differentiation commitment result from a differentiation-stimulus driven variable and slow increase in expression of PPARG, the master regulator of adipogenesis, overlaid with circadian boosts in PPARG expression driven by fast, clock-driven PPARG regulators such as CEBPA. Our finding of daily bursts in cell differentiation only during the circadian cycle phase corresponding to evening in humans is broadly relevant, given that most differentiating somatic cells are regulated by the circadian clock. Having a restricted time each day when differentiation occurs may open therapeutic strategies to use timed treatment relative to the clock to promote tissue regeneration.

The prevalence of obesity and its associated pathologies continue to increase, which has led to a renewed interest in our major weight-regulating organ, the white adipose tissue. It has become clear that its development, expansion, and physiological function depend on proper crosstalk between each of its cellular constituents, with a central role for the vascular endothelium lining the blood vessels. Although first considered a mere barrier, the endothelium has emerged as a dynamic unit modulating many critical adipose tissue functions. It not only oversees the uptake of all nutrients to be stored in the adipocytes but also provides an important growth niche for adipocyte progenitors and regulates the expandability of the tissue during overfeeding and obesity. In this review, we describe the reciprocal relationship between endothelial cells, adipocytes, and obesity. We present recent studies that support an important role for endothelial cells as central mediators of many of the physiological and pathological functions of the adipose tissue and highlight several unknown aspects of adipose tissue vascular biology. This new perspective could present exciting opportunities to develop new therapeutic approaches against obesity-related pathologies and is thus of great interest in our increasingly obese society., (© 2021 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

In vitro models of adipogenesis are phenotypic assays that most closely mimic the increase of adipose tissue in obesity. Current models, however, often lack throughput and sensitivity and even report conflicting data regarding adipogenic potencies of many chemicals. Here, we describe a ten-day long adipogenesis model using high content analysis readouts for adipocyte number, size, and lipid content on primary human mesenchymal stem cells (MSC) sensitive enough to compare bisphenol A derivatives quantitatively in a robust and high throughput manner. The number of adipocytes was the most sensitive endpoint capable of detecting changes of 20% and was used to develop a benchmark concentration model (BMC) to quantitatively compare eight bisphenols (tested at 0.1-100 μM). The model was applied to evaluate mixtures of bisphenols obtaining the first experimental evidence of their additive effect on human MSC adipogenesis. Using the relative potency factors (RPFs), we show how a mixture of bisphenols at their sub-active concentrations induces a significant adipogenic effect due to its additive nature. The final active concentrations of bisphenols in tested mixtures reached below 1 μM, which is within the concentration range observed in humans. These results point to the need to consider the toxicity of chemical mixtures., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Adipose tissue (AT) expands by a combination of two fundamental cellular mechanisms: hypertrophic growth of existing adipocytes or through generation of new adipocytes, also known as hyperplastic growth. Multiple lines of evidence suggest a limited capacity for hyperplastic growth of AT in adulthood and that adipocyte number is relatively stable, even with fluctuations in AT mass. If the adipocyte number is stable in adulthood, despite well-documented birth and death of adipocytes, then this would suggest that birth may be coupled to death in a regenerative cycle. To test this hypothesis, we examined the dynamics of birth of new fat cells in relationship to adipocyte death by using high-fidelity stable isotope tracer methods in C57Bl6 mice. We discovered birth of new adipocytes at higher frequency in histological proximity to dead adipocytes. In diet-induced obesity, adipogenesis surged after an adipocyte death peak beyond 8 weeks of high-fat feeding. Through transcriptional analyses of AT and fractionated adipocytes, we found that the dominant cell death signals were inflammasome related. Proinflammatory signals were particularly evident in hypertrophied adipocytes or with deletion of a constitutive oxygen sensor and inhibitor of hypoxia-inducible factor, Egln1. We leveraged the potential role for the inflammasome in adipocyte death to test the adipocyte death-birth hypothesis, finding that caspase 1 loss of function attenuated adipocyte death and birth in murine visceral AT. These data collectively point to a regenerative cycle of adipocyte death and birth as a driver of adipogenesis in adult murine AT., (© 2022 by the American Diabetes Association.)

Adipogenesis is dependent on cytoskeletal remodeling that determines and maintains cellular shape and function. Cytoskeletal proteins contribute to the filament-based network responsible for controlling the shape of adipocytes and promoting the intracellular trafficking of cellular components. Currently, the understanding of these mechanisms and their effect on differentiation and adipocyte function remains incomplete. In this study, we identified the non-muscle myosin 10 (MYH10) as a novel regulator of adipogenesis and adipocyte function through its interaction with the insulin-dependent glucose transporter 4 (GLUT4). MYH10 depletion in preadipocytes resulted in impaired adipogenesis, with knockdown cells exhibiting an absence of morphological alteration and molecular signals. MYH10 was shown in a complex with GLUT4 in adipocytes, an interaction regulated by insulin induction. The missing adipogenic capacity of MYH10 knockdown cells was restored when the cells took up GLUT4 vesicles from neighbor wildtype cells in a co-culture system. This signaling cascade is regulated by the protein kinase C ζ (PKCζ), which interacts with MYH10 to modify the localization and interaction of both GLUT4 and MYH10 in adipocytes. Overall, our study establishes MYH10 as an essential regulator of GLUT4 translocation, affecting both adipogenesis and adipocyte function, highlighting its importance in future cytoskeleton-based studies in adipocytes.

Pancreatic steatosis associates with β-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.

Stem cells (SC) are largely known for their potential to restore damaged tissue through various known mechanisms. Among these mechanisms is their ability to transfer healthy mitochondria to injured cells to rescue them. This mitochondrial transfer plays a critical role in the healing process. To determine the optimal parameters for inducing mitochondrial transfer between cells, we assessed mitochondrial transfer as a function of seeding density and in two-dimensional (2D) and semi three-dimensional (2.5D) culture models. Since mitochondrial transfer can occur through direct contact or secretion, the 2.5D culture model utilizes collagen to provide cells with a more physiologically relevant extracellular matrix and offers a more realistic representation of cell attachment and movement. Results demonstrate the dependence of mitochondrial transfer on cell density and the distance between donor and recipient cell. Furthermore, the differences found between the transfer of mitochondria in 2D and 2.5D microenvironments suggest an optimal mode of mitochondria transport. Using these parameters, we explored the effects on mitochondrial transfer between SCs and tumorigenic cells. HEK293 (HEK) is an immortalized cell line derived from human embryonic kidney cells which grow rapidly and form tumors in culture. Consequently, HEKs have been deemed tumorigenic and are widely used in cancer research. We observed mitochondrial transfer from SCs to HEK cells at significantly higher transfer rates when compared to a SC-SC co-culture system. Interestingly, our results also revealed an increase in the migratory ability of HEK cells when cultured with SCs. As more researchers find co-localization of stem cells and tumors in the human body, these results could be used to better understand their biological relationship and lead to enhanced therapeutic applications.

In high-yielding dairy cows, the rapidly increasing milk production after parturition can result in a negative nutrient balance, since feed intake is insufficient to cover the needs for lactation. Mobilizing body reserves, mainly adipose tissue (AT), might affect steroid metabolism. We hypothesized, that cows differing in the extent of periparturient lipomobilization, will have divergent steroid profiles measured in serum and subcutaneous (sc)AT by a targeted metabolomics approach and steroidogenic enzyme profiles in scAT and liver. Fifteen weeks antepartum, 38 multiparous Holstein cows were allocated to a high (HBCS) or normal body condition (NBCS) group fed differently until week 7 antepartum to either increase (HBCS BCS: 3.8 ± 0.1 and BFT: 2.0 ± 0.1 cm; mean ± SEM) or maintain BCS (NBCS BCS: 3.0 ± 0.1 and BFT: 0.9 ± 0.1 cm). Blood samples, liver, and scAT biopsies were collected at week -7, 1, 3, and 12 relative to parturition. Greater serum concentrations of progesterone, androsterone, and aldosterone in HBCS compared to NBCS cows after parturition, might be attributed to the increased mobilization of AT. Greater glucocorticoid concentrations in scAT after parturition in NBCS cows might either influence local lipogenesis by differentiation of preadipocytes into mature adipocytes and/or inflammatory response., (© 2022. The Author(s).)

Octocrylene (OC) is an extensively prescribed organic ultraviolet B filter used in sunscreen products. Due to its extensive use, a significant level of OC is detected in marine and freshwater environments. Notably, the bioaccumulation of OC in aquatic biota may affect human health. In this study, the effect of OC on metabolism was investigated using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs). OC promoted adiponectin production during adipogenesis in hBM-MSCs compared to the vehicle-treated control (EC 50 , 29.6 μM). In target identification, OC directly bound to peroxisome proliferator-activated receptor (PPAR) γ (Ki, 37.8 μM). OC-bound PPARγ also significantly recruited nuclear receptor coactivator proteins SRC-1 (EC 50 , 54.1 μM) and SRC-2 (EC 50 , 58.6 μM). In the molecular docking simulation study, the optimal ligand-binding mode of OC suggested that OC is a PPARγ partial agonist. A competitive analysis with a PPARγ full agonist pioglitazone revealed that OC acted as a PPARγ partial agonist. OC altered the gene transcription profile of lipid-metabolism associated enzymes in normal human keratinocytes, primarily exposed human cells after the application of sunscreens. In conclusion, OC is a potential metabolic disrupting obesogen., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021. Published by Elsevier B.V.)

Marbling influences the taste and tenderness of meat and is the main determinant of carcass quality in many countries. This study aims to investigate the influence of KLF6 (Kruppel Like Factor 6) and associated molecular mechanisms on lipid metabolism in bovine adipocytes. In the current study, KLF6 gene expression was down regulated via siRNA (small interfering RNA) in bovine adipocytes in vitro. Subsequently, adipogenic cells were collected from the culture media after 9 days, and subjected to fluorescent imaging and RNA sequencing. After confirming that KLF6 was down regulated in bovine adipocytes by siRNA, differential gene expression analysis was used to characterize the infuence of KLF6 on gene expression profiles in bovine adipocytes. A total of 10,812 genes were characterized as differentially expressed genes (DEGs) of which, 109 were up-regulated and 62 were down-regulated genes. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis identified that the DEGs were associated with lipid metabolism, carbohydrate metabolism, cell growth and death, cancer, and the signaling pathways for calcium, AMPK (Adenosine Monophosphate-Activated Protein Kinase), PI3K-Akt (Phosphatidylinositol 3-kinase), PPAR (Peroxisome proliferator-activated receptors), MAPK (mitogen-activated protein kinase), cAMP (Cyclic adenosine monophosphate), and Wnt (Wingless-related integration site). Similarly, gene ontology analysis indicated that down-regulation of KLF6 gene significantly up regulated the genes that regulate adipogenesis, differentiation and regulation of adipocytes and homeostasis of bovine adipocytes, specifically regulating the cell-type specific apoptotic action, negative regulation of apoptotic pathways, programmed cell death, and growth. Results indicate that KLF6 has a role in regulating lipid metabolism in bovine adipocytes. These findings provide evidence that may inform further investigations into molecular mechanisms that underlie the role of bovine KLF6 gene in regulating adipogenesis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

As the largest energy storage reservoir, subcutaneous adipose tissue (SAT) stores excess lipids by adipocytes enlargement and/or recruitment of new precursor cells. Energy overload can cause ectopic fat deposition and metabolic diseases. In this study, 6814 differentially expressed genes (DEGs) were screened in goat subcutaneous preadipocytes and mature adipocytes by RNA-seq technique. The relative expression of the DEGs were verified by qPCR, such as PLIN2, MECR, ADCY7, PEBP1 and KLF5, and their expression level was found to be consistent with the trend of RNA-seq analysis. The KLF5 was selected for further functional verification. Overexpression of KLF5 promoted both the adipogenesis and the differentiation of preadipocytes, while the expression of preadipocyte marker gene: preadipocyte factor 1(Pref1) was decreased, as well as, peroxisome proliferator activation Receptor γ(PPARγ), CCAAT enhancer binding protein β(C/EBPβ) and Sterol regulatory element binding protein isoform 1(SREBP1) were increased. On the contrary, the interference of KLF5 could reduce adipogenesis, enhance the expression of Pref1, and reduce the expression of C/EBPβ and SREBP1. Our research provides a basic reference for revealing the mechanism of subcutaneous adipocyte differentiation in goats., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic or acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions of the gonadotropic axis and endocrine defects of adipose tissue with leptin and adiponectin deficiency. Diagnosis, based on clinical and metabolic investigations, and on genetic analyses, is of major importance to adapt medical care and genetic counseling. Molecular and cellular bases of these syndromes involve, among others, altered adipocyte differentiation, structure and/or regulation of the adipocyte lipid droplet, and/or premature cellular senescence. Lipodystrophy syndromes frequently present as systemic diseases with multi-tissue involvement. After an update on the main molecular bases and clinical forms of lipodystrophy, we will focus on topics that have recently emerged in the field. We will discuss the links between lipodystrophy and premature ageing and/or immuno-inflammatory aggressions of adipose tissue, as well as the relationships between lipomatosis and lipodystrophy. Finally, the indications of substitutive therapy with metreleptin, an analog of leptin, which is approved in Europe and USA, will be discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zammouri, Vatier, Capel, Auclair, Storey-London, Bismuth, Mosbah, Donadille, Janmaat, Fève, Jéru and Vigouroux.)

Objective: Adipogenesis plays an essential role in maintaining energy and hormonal balance. Cavin-2, one of the caveolae-related proteins, is abundant in adipocytes, the leading site of adipogenesis. However, the details of the roles of Cavin-2 in adipogenesis remain unknown. Here, we demonstrate the requirement of Cavin-2 for the expression and stability of IRβ in adequate adipocyte differentiation., Methods: Cavin-2 knockout (Cavin-2 KO) and wild-type (WT) mice were fed with a high-fat diet (HFD) for 8 weeks. We evaluated body weight, food intake, and several tissues. Glucose homeostasis was assessed by glucose and insulin tolerance tests. Insulin signaling in epididymal white adipose tissue (eWAT) was determined by Akt phosphorylation. In vitro study, we evaluated adipocyte differentiation, adipogenesis-related genes, and insulin signaling to clarify the relationship between Cavin-2 and adipogenesis under the manipulation of Cavin-2 expression., Results: Caveolae structure decreased in eWAT of Cavin-2 KO mice and Cavin-2 knockdown 3T3-L1 cells. Cavin-2 enhanced the stability of insulin receptor (IR) through direct association at the plasma membrane in adipocytes, resulting in accelerated insulin/IR/Akt signaling-induced adipogenic gene expression in insulin-containing solution-stimulated 3T3-L1 adipocytes. IR-mediated Akt activation also enhanced Cavin-2 and IR expression. Cavin-2 knockout mice showed insulin resistance with dyslipidemia and pathological hypertrophic adipocytes after a HFD., Conclusions: Cavin-2 enhances IR stability through binding IR and regulates insulin signaling, promoting adequate adipocyte differentiation. Our findings highlight the pivotal role of Cavin-2 in adipogenesis and lipid metabolism, which may help to develop novel therapies for pathological obesity and adipogenic disorders., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Obesity is associated with the risk of venous thromboembolism. Thrombi are constantly formed via the coagulation cascade and degraded by the fibrinolytic system, so they tend to form in obese individuals. Adipocytes are involved in thrombus formation in obesity, but it is not clear whether bioactive factors from adipocytes directly initiate or enhance coagulation and thrombosis. In this study, we confirmed that adipocyte-derived extracellular vesicles (ADEVs) enhance procoagulant activity in vitro. ADEVs prepared from the culture supernatant of mature 3T3-L1 adipocytes shortened plasma clotting times. Moreover, the effect of ADEVs on clotting time was weakened when using plasma lacking factors of the extrinsic pathway, but not the intrinsic pathway. ADEVs contain tissue factors and phosphatidylserine, which are involved in the extrinsic pathway, and blockade of these molecules diminished the effects of ADEVs on plasma clotting time. Additionally, the effect of ADEVs on plasma clotting time was further enhanced when cells were stimulated with the proinflammatory cytokine tumor necrosis factor-α. Thus, ADEVs may be a factor in thrombus formation in obesity.

Background: Leptin resistance occurs in obese patients, but its independent contribution to adiposity and the accompanying metabolic diseases, i.e., diabetes, liver steatosis, and steatohepatitis, remains to be established. This study was conducted in an extreme model of leptin resistance to investigate mechanisms initiating diabetes, fat expansion, liver steatosis, and inflammatory disease, focusing on the involvement of glucose intolerance and organ-specific glucose uptake in brown and subcutaneous adipose tissues (BAT, SAT) and in the liver., Methods: We studied preobese and adult Zucker rats (fa/fa, fa/+ ) during fasting or glucose loading to assess glucose tolerance. Relevant pancreatic and intestinal hormonal levels were measured by Milliplex. Imaging of 18 F-fluorodeoxyglucose by positron emission tomography was used to quantify glucose uptake in SAT, BAT, and liver, and evaluate its relationship with adipocyte size and biopsy-proven nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH)., Results: Preobese fa/fa pups showed impaired glucose tolerance, adipocyte enlargement, hepatic microsteatosis, and lobular inflammation, with elevated hepatic post-glucose load glucose uptake and production. Adult fa/fa rats had more severe glucose intolerance, fasting hyperglycemia, hormonal abnormalities, elevated glucose uptake in SAT and BAT, and more markedly in the liver, together with macrosteatosis, and highly prevalent hepatic inflammation. Organ glucose uptake was proportional to the degree of fat accumulation and tissue inflammation and was able to dissect healthy from NAFLD and NAFLD/NASH livers. Most severe NASH livers showed a decline in glucose uptake and liver enzymes., Conclusions: In fa/fa Zucker rats, leptin resistance leads to glucose intolerance, mainly due to hepatic glucose overproduction, preceding obesity, and explaining pancreatic and intestinal hormonal changes and fat accumulation in adipocytes and hepatocytes. Our data support the involvement of liver glucose uptake in the pathogenesis of liver inflammatory disease. Its potential as more generalized biomarker or diagnostic approach remains to be established outside of our leptin-receptor-deficient rat model., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

It is primarily important to define the standard features and factors that affect dental pulp stem cells (DPSCs) for their broader use in tissue engineering. This study aimed to verify whether DPSCs isolated from various teeth extracted from the same donor exhibit intra-individual variability and what the consequences are for their differentiation potential. The heterogeneity determination was based on studying the proliferative capacity, viability, expression of phenotypic markers, and relative length of telomere chromosomes. The study included 14 teeth (6 molars and 8 premolars) from six different individuals ages 12 to 16. We did not observe any significant intra-individual variability in DPSC size, proliferation rate, viability, or relative telomere length change within lineages isolated from different teeth but the same donor. The minor non-significant variances in phenotype were probably mainly because DPSC cell lines comprised heterogeneous groups of undifferentiated cells independent of the donor. The other variances were seen in DPSC lineages isolated from the same donor, but the teeth were in different stages of root development. We also did not observe any changes in the ability of cells to differentiate into mature cell lines-chondrocytes, osteocytes, and adipocytes. This study is the first to analyze the heterogeneity of DPSC dependent on a donor.

Thyroid hormone (TH) and thyroid hormone receptor (THR) regulate stem cell proliferation and differentiation during development, as well as during tissue renewal and repair in the adult. THR undergoes posttranslational modification by small ubiquitin-like modifier (SUMO). We generated the THRA (K283Q/K288R) -/- mouse model for in vivo studies and used human primary preadipocytes expressing the THRA sumoylation mutant (K283R/K288R) and isolated preadipocytes from mutant mice for in vitro studies. THRA mutant mice had reduced white adipose stores and reduced adipocyte cell diameter on a chow diet, compared to wild-type, and these differences were further enhanced after a high fat diet. Reduced preadipocyte proliferation in mutant mice, compared to wt, was shown after in vivo labeling of preadipocytes with EdU and in preadipocytes isolated from mice fat stores and studied in vitro. Mice with the desumoylated THRA had disruptions in cell cycle G 1 /S transition and this was associated with a reduction in the availability of cyclin D2 and cyclin-dependent kinase 2. The genes coding for cyclin D1, cyclin D2, cyclin-dependent kinase 2 and Culin3 are stimulated by cAMP Response Element Binding Protein (CREB) and contain CREB Response Elements (CREs) in their regulatory regions. We demonstrate, by Chromatin Immunoprecipitation (ChIP) assay, that in mice with the THRA K283Q/K288R mutant there was reduced CREB binding to the CRE. Mice with a THRA sumoylation mutant had reduced fat stores on chow and high fat diets and reduced adipocyte diameter., (© 2021. The Author(s).)

Background: Recently, lineage-tracing studies demonstrated that parathyroid hormone and anti-sclerostin antibody (Scl-Ab) can convert bone lining cells (BLCs) into active osteoblasts. However, BLCs might also be differentiated into other lineages. Here we investigated whether BLCs could differentiate into bone marrow adipocytes (BMAds) and whether Scl-Ab could suppress this process., Methods: Dmp1-CreERt2:mTmG mice were injected with 0.5 mg of 4-hydroxytamoxifen once weekly from postnatal week 4 to week 8. The mice were treated with either vehicle or rosiglitazone for 8 weeks (weeks 12-20). Moreover, they were administered either vehicle or Scl-Ab (50 mg/kg) twice weekly for 4 weeks (weeks 16-20, N = 4-6/group). We chased the GFP+ cells from the endosteal surface to the bone marrow (BM) of the femur. Using immunohistochemical staining, the numbers of perilipin+ or GFP+/perilipin double+ cells in the BM were quantified. In addition, serum N-terminal propeptide of type I procollagen (P1NP) levels were measured at each time point, and bone mass was analyzed at 20 weeks using micro-computed tomography., Results: Scl-Ab administration significantly reversed the decreases in bone parameters induced by rosiglitazone. Plump GFP+ cells, presumably active osteoblasts, and extremely flat GFP+ cells, presumably BLCs, were present on the endosteal surface of the femur at 8 and 12 weeks, respectively, in line with prior findings. When we chased the GFP+ cells, rosiglitazone significantly increased the number of GFP/perilipin double+ BMAds compared to the effects of the vehicle (P < 0.001), and overlapping Scl-Ab administration decreased the number of GFP/perilipin double + BMAd compared to rosiglitazone alone (P < 0.001). In addition, we found that osteoblast lineage cells such as BLCs might express PPARγ on immunohistochemical staining. When rosiglitazone was administered to Rip-Cre:mTmG mice, GFP+ cells were not present on the endosteal surface or in the BM of the femur; however, they were present in the pancreas., Conclusion: BLCs could be sources of BMAds, and rosiglitazone could stimulate the differentiation of osteoblast lineage cells into BMAds. Suppression of the differentiation of osteoblast lineage cells into BMAds might contribute to anabolic effects resulting from the pharmacologic inhibition of sclerostin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Yang and Kim.)

Our understanding of adipose tissue has progressed from an inert tissue for energy storage to be one of the largest endocrine organs regulating metabolic homoeostasis through its ability to synthesize and release various adipokines that regulate a myriad of pathways. The field of adipose tissue biology is growing due to this association with various chronic metabolic diseases. An important process in the regulation of adipose tissue biology is adipogenesis, which is the formation of new adipocytes. Investigating adipogenesis in vitro is currently a focus for identifying factors that might be utilized in clinically. A powerful tool for such work is high-throughput sequencing which can rapidly identify changes at gene expression level. Various cell models exist for studying adipogenesis and has been used in high-throughput studies, yet little is known about transcriptome profile that underlies adipogenesis in mouse embryonic fibroblasts. This study utilizes RNA-sequencing and computational analysis with DESeq2, gene ontology, protein-protein networks, and robust rank analysis to understand adipogenesis in mouse embryonic fibroblasts in-depth. Our analyses confirmed the requirement of mitotic clonal expansion prior to adipogenesis in this cell model and highlight the role of  Cebpa  and  Cebpb  in regulating adipogenesis through interactions of large numbers of genes.

The mesenchymal components of the hair follicle-the dermal papilla (DP) and dermal sheath (DS)-are maintained by hair follicle dermal stem cells, but the position of this stem cell population throughout the hair cycle, its contribution to the maintenance of the dermis, and the existence of a migratory axis from the DP to the dermis remain unclear. In this study, we show that during homeostasis DP and DS cells are confined to their compartments, and during the regression phase of the hair cycle, some DP/DS cells undergo apoptosis and subsequently are internalized by nearby adipocytes. In contrast, during wound healing, DP/DS cells move toward the wound but do not directly participate in follicle neogenesis. Furthermore, hair follicle dermal stem cells, driving the cyclic renewal of the DS during the hair cycle, are heterogeneous and are housed during the growth phase within the most proximal part of the DS. Our analysis provides insight into the mechanisms of tissue maintenance and reveals a potential function of adipocytes in phagocytosis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Intramuscular fat content, an important meat quality trait, strongly affects flavor, juiciness, and tenderness. Sex hormones regulate lipid metabolism, and female hormones stimulate fat deposition, thereby making the female chickens always fatter than males. In this study, the effect of sex on IMF deposition was screened following transcriptomics in chickens., Methods and Results: Results confirmed significantly higher IMF content of 150-day female chickens as compared to the male chickens. The female chickens manifested higher serum TG, LDL-C, and VLDL, and significantly lower HDL-C contents than male chickens. Moreover, differential expression of genes involved in lipid metabolism were obtained in the muscle and liver between female and male chicken, which could partly interpret the possible reasons for the sex-mediated differences of IMF content. Cellular results revealed that inhibition of PLIN2 significantly inhibited chicken preadipocyte proliferation and induces apoptosis of preadipocytes, as well as promoted adipocyte differentiation., Conclusions: According to our results, PLIN2 may be considered as a molecular marker for poultry meat quality and applying this gene in early breed selection., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Lipodystrophic syndromes (LS) constitute a clinically and genetically heterogeneous group of diseases characterized by a loss of adipose tissue. These syndromes are usually associated with metabolic complications, which are determinant for morbidity and mortality. The classical forms of LS include partial, generalized, and progeroid lipodystrophies. They are usually due to defects in proteins playing a key role in adipogenesis and adipocyte functions. More recently, systemic disorders combining lipodystrophy and multiple organ dysfunction have been described, including autoinflammatory syndromes, mitochondrial disorders, as well as other complex entities. To date, more than thirty genes have been implicated in the monogenic forms of LS, but the majority of them remain genetically-unexplained. The associated pathophysiological mechanisms also remain to be clarified in many instances. Next generation sequencing-based approaches allow simultaneous testing of multiple genes and have become crucial to speed up the identification of new disease-causing genes. The challenge for geneticists is now the interpretation of the amount of available genetic data, generated especially by exome and whole-genome sequencing. International recommendations on the interpretation and classification of variants have been set up and are regularly reassessed. Very close collaboration between geneticists, clinicians, and researchers will be necessary to make rapid progress in understanding the molecular and cellular basis of these diseases, and to promote personalized medicine., Competing Interests: Disclosure of interest The author declares that she has no conflict of interest concerning this article, (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The mammalian focal adhesion proteins Pinch1/2 activate integrins and promote cell-extracellular matrix adhesion and migration; however, their roles in adipose tissue and metabolism are unclear. Here we find that high-fat diet (HFD) feeding dramatically increases expression of Pinch1/2 proteins in white adipose tissue (WAT) in mice. Furthermore, expression of Pinch1 is largely upregulated in WAT in leptin-deficient ob / ob type 2 diabetic mice and obese humans. While mice with loss of Pinch1 in adipocytes or global Pinch2 do not display any notable phenotypes, deleting Pinch1 in adipocytes and Pinch2 globally significantly decreases body weight and WAT mass, but not brown adipose tissue mass, in HFD-fed, but not normal chow diet-fed, mice. Pinch loss ameliorates HFD-induced glucose intolerance and fatty liver. After HFD challenge, Pinch loss slightly but significantly accelerates energy expenditure. While Pinch loss decreases adipocyte size and alters adipocyte size distribution, it greatly accelerates cell apoptosis primarily in epididymal WAT and to a lesser extent in subcutaneous WAT. In vitro studies demonstrate that Pinch loss accelerates adipocyte apoptosis by activating the Bim/Caspase-8 pathway. In vivo, genetic ablation of Caspase-8 expression in adipocytes essentially abolishes the ameliorating effects of Pinch deficiency on obesity, glucose intolerance, and fatty liver in mice. Thus, we demonstrate a previously unknown function of Pinch in control of adipose mass, glucose, and fat metabolism via modulation of adipocyte apoptosis. We may define a novel target for the prevention and treatment of metabolic diseases, such as obesity and diabetes., (© 2021 by the American Diabetes Association.)

Eight compounds (1-8) including one novel nitrophenyl glycoside, ginkgonitroside (1) were isolated from the leaves of Ginkgo biloba, a popular medicinal plant. The structure of the new compound was characterized using extensive spectroscopic analyses via 1D and 2D NMR data interpretations, HR-ESIMS, and chemical transformation. To the best of our knowledge, the present study is the first to report the presence of nitrophenyl glycosides, which are relatively unique phytochemicals in natural products, in G. biloba. The isolated compounds (1-8) were examined for their effects on the regulation of mesenchymal stem cell (MSC) differentiation. Compounds 1-3 and 8 were able to suppress MSC differentiation toward adipocytes. In contrast, compounds 5 and 8 showed activity promoting osteogenic differentiation of MSCs. These findings demonstrate that the active compounds showed regulatory activity on MSC differentiation between adipocytes and osteocytes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Metabolic syndrome caused obesity has long been recognized as a risk of health. Celery and celery extracts have various medicinal properties, such as anti-diabetes and anti-inflammatory properties and blood glucose and serum lipid reduction. However, the effect of probiotic fermentation on celery juice and the association between fermented celery juice (FCJ) and obesity were unclear. This study aimed to evaluate the beneficial effects of FCJ on high-fat diet (HFD) induced obesity and related metabolic syndromes. C57BL/6 mice were randomly divided into six groups ( n = 15 per group) fed either a normal diet (ND) or HFD with or without CJ/FCJ (10 g kg -1 day -1 ) by oral gavage for 12 weeks. Here we demonstrated that the probiotic fermentation of celery juice (CJ) could enhance the active ingredients in celery, such as total polyphenols, flavonoids, vitamin C and SOD. Compared to the slight improvement induced by CJ ingestion, FCJ intake significantly inhibited body weight gain, prevented dyslipidemia and hyperglycemia, and suppressed visceral fat accumulation. Furthermore, 16S rRNA sequencing analysis revealed that FCJ intake altered the composition of gut microbiota, increasing the ratio of Firmicutes / Bacteroidetes and the relative abundance of beneficial bacteria ( Lactobacillus , Ruminococcaceae&#95;UCG-014 , Faecalibaculum and Blautia ), and decreasing the relative abundance of harmful bacteria ( Alloprevotella and Helicobacter ). These findings suggest that FCJ can prevent HFD-induced obesity and become a novel gut microbiota modulator to prevent HFD-induced gut dysbiosis and obesity-related metabolic disorders.