23 results on '"white fat"'
Search Results
2. Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism.
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Zhang, Peiwen, He, Yuxu, Wu, Shuang, Li, Xinrong, Lin, Xutao, Gan, Mailin, Chen, Lei, Zhao, Ye, Niu, Lili, Zhang, Shunhua, Li, Xuewei, Zhu, Li, and Shen, Linyuan
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WHITE adipose tissue , *BROWN adipose tissue , *LIPID metabolism , *ADIPOSE tissues , *LIPID metabolism disorders , *GLUCOSE metabolism disorders , *FAT cells - Abstract
Mammalian adipose tissue can be divided into white and brown adipose tissue based on its colour, location, and cellular structure. Certain conditions, such as sympathetic nerve excitement, can induce the white adipose adipocytes into a new type of adipocytes, known as beige adipocytes. The process, leading to the conversion of white adipocytes into beige adipocytes, is called white fat browning. The dynamic balance between white and beige adipocytes is closely related to the body's metabolic homeostasis. Studying the signal transduction pathways of the white fat browning might provide novel ideas for the treatment of obesity and alleviation of obesity-related glucose and lipid metabolism disorders. This article aimed to provide an overview of recent advances in understanding white fat browning and the role of BAT in lipid metabolism. [ABSTRACT FROM AUTHOR]
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- 2022
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3. 低温运动干预肥胖大鼠的脂肪组织类型及功能改变.
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王朝格, 翁锡全, 林宝璇, 陈丽娜, and 徐国琴
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WHITE adipose tissue , *UNCOUPLING proteins , *BROWN adipose tissue , *FAT , *TREADMILL exercise , *FAT cells , *SOLITARY nucleus - Abstract
BACKGROUND: Cold exposure and exercise serve as two powerful physiological stimuli to change the type and function of fat, which has positive implications for the treatment of obesity and related metabolic diseases. So far, it remains to be unclear whether exercise in the different cold exposure can produce an addictive effect on fat change. OBJECTIVE: To observe the browning effect of white fat and the expression of uncoupling protein 1 in obese rats after 5 weeks of exercise intervention under cold exposure. METHODS: Sixty-four Sprague-Dawley rats were selected to establish animal models of nutritional obesity. They were randomly divided into four groups: normal control group (NTS), normal exercise group (NTE), acute cold control group (ACS), acute cold exercise group (ACE), intermittent cold control group (ICS) and intermittent cold exercise group (ICE), continuous cold control group (CES), and continuous cold exercise group (CEE). The normal temperature environment was 24-26 °C, the cold environment was 3-4 °C, and the relative humidity was 50%-60%. For acute cold exposure, the rats were exposed to low temperature for only 4 hours before the end of the experiment; for intermittent cold exposure, the rats were exposed to low temperature for 4 hours per day; for continuous cold exposure, the rats stayed in a cold environment all day. The protocol for treadmill running in exercise groups was as follows: 25 m/min (speed), 0 °C (slope), 30 minutes once, for two sections. Sampling was conducted after 5 weeks. The fat rate was measured by Micro-CT LCT200. The interscapular and inguinal fats were collected for hematoxylin-eosin staining to observe morphological changes, and the expression of uncoupling protein 1 in the inguinal fat was examined by western blot. RESULTS AND CONCLUSION: In the CES, ICE and CEE groups, the volume of interscapular fat cells decreased significantly and the cell number increased significantly; the lipid droplets gradually disappeared and the intercellular capillaries gradually increased. The white fat cells in the inguinal of the rats in the ICE and SEE groups were multilocular, with smaller and more uniform cell size and tighter tissue, showing an obvious browning trend. Compared with the CEE group, the visceral and body fat rate were significantly declined in the NTS, NTE, ACS, ACE, ICS and CES groups (P < 0.05). The subcutaneous fat rate of the NTS group was significantly declined compared with that of the ACS and ICS groups (P < 0.05), and that of the ACE group was significantly declined compared with that of the NTE group (P < 0.05). Compared with the NTS group, the brown fat rate was significantly higher in the ACS, ICS, CES and CEE groups (P < 0.05); compared with the ACE group, the brown fat rate was significantly higher in ACS group (P < 0.05); compared with the ICE group, the brown fat rate was significantly higher in ICS group (P < 0.05); compared with the ACE group, the brown fat rate was significantly declined in ICE and CEE groups (P < 0.05). The expression of uncoupling protein 1 in each exercise group was significantly up-regulated compared with the corresponding control group (P < 0.05). The expression of uncoupling protein 1 was lowest in the NTS group, and highest in CCE group, followed by the ICE group (P < 0.05). To conclude, exercises under continuous and intermittent cold exposure can induce the browning of subcutaneous inguinal white fat and reduce the body fat rate of obese body, which may be correlated with the morphological changes of inguinal fat as well as the changes of uncoupling protein 1. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Dlgap1 negatively regulates browning of white fat cells through effects on cell proliferation and apoptosis.
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Zhang, Ju, Yang, Jie, Yang, Nan, Ma, Jianfei, Lu, Datong, Dong, Yanhua, Liang, Hao, Liu, Dongjun, and Cang, Ming
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WHITE adipose tissue , *FAT cells , *BROWN adipose tissue , *LEUCOCYTES , *CELL proliferation , *ADIPOGENESIS - Abstract
Background: Obesity is a metabolic imbalance characterized by excessive deposition of white fat. The browning of white fat can effectively treat obesity and related diseases. Although Dlgap1 (Discs, Large (Drosophila) Homolog-Associated Protein 1) is suspected to have an effect on this process, no empirical evidence is available. Methods: To understand the role of Dlgap1, we cultured white and brown fat cells, then performed overexpression and knockout experiments. Results: We found that Dlgap1 overexpression in brown adipocytes inhibits brown-fat-related gene expression, promotes white-fat-related genes, while also increasing brown-adipocyte proliferation and apoptosis. However, the gene overexpression has no effect on brown adipocyte maturation. Knocking out Dlgap1 in white fat cells promotes the expression and inhibition of brown-fat-related and white-fat-related genes, respectively. Additionally, the knockout inhibits white fat cell proliferation and apoptosis, while also promoting their maturation. Conclusions: Dlgap1 negatively regulates the browning of white adipocytes by influencing cell proliferation and apoptosis. [ABSTRACT FROM AUTHOR]
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- 2020
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5. Differentiating supraclavicular from gluteal adipose tissue based on simultaneous PDFF and T2 * mapping using a 20-echo gradient-echo acquisition.
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Franz, Daniela, Diefenbach, Maximilian N., Treibel, Franziska, Weidlich, Dominik, Syväri, Jan, Ruschke, Stefan, Wu, Mingming, Holzapfel, Christina, Drabsch, Theresa, Baum, Thomas, Eggers, Holger, Rummeny, Ernst J., Hauner, Hans, and Karampinos, Dimitrios C.
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ADIPOSE tissues ,WHITE adipose tissue ,BROWN adipose tissue ,WILCOXON signed-rank test ,STANDARD deviations ,BUTTOCKS ,CLAVICLE ,COMPARATIVE studies ,LONGITUDINAL method ,MAGNETIC resonance imaging ,RESEARCH methodology ,MEDICAL cooperation ,REFERENCE values ,RESEARCH ,EVALUATION research - Abstract
Background: Adipose tissue (AT) can be classified into white and brown/beige subtypes. Chemical shift encoding-based water-fat MRI-techniques allowing simultaneous mapping of proton density fat fraction (PDFF) and T2 * result in a lower PDFF and a shorter T2 * in brown compared with white AT. However, AT T2 * values vary widely in the literature and are primarily based on 6-echo data. Increasing the number of echoes in a multiecho gradient-echo acquisition is expected to increase the precision of AT T2 * mapping.Purpose: 1) To mitigate issues of current T2 *-measurement techniques through experimental design, and 2) to investigate gluteal and supraclavicular AT T2 * and PDFF and their relationship using a 20-echo gradient-echo acquisition.Study Type: Prospective.Subjects: Twenty-one healthy subjects.Field Strength/sequence Assessment: First, a ground truth signal evolution was simulated from a single-T2 * water-fat model. Second, a time-interleaved 20-echo gradient-echo sequence with monopolar gradients of neck and abdomen/pelvis at 3 T was performed in vivo to determine supraclavicular and gluteal PDFF and T2 *. Complex-based water-fat separation was performed for the first 6 echoes and the full 20 echoes. AT depots were segmented.Statistical Tests: Mann-Whitney test, Wilcoxon signed-rank test and simple linear regression analysis.Results: Both PDFF and T2 * differed significantly between supraclavicular and gluteal AT with 6 and 20 echoes (PDFF: P < 0.0001 each, T2 *: P = 0.03 / P < 0.0001 for 6/20 echoes). 6-echo T2 * demonstrated higher standard deviations and broader ranges than 20-echo T2 *. Regression analyses revealed a strong relationship between PDFF and T2 * values per AT compartment (R2 = 0.63 supraclavicular, R2 = 0.86 gluteal, P < 0.0001 each).Data Conclusion: The present findings suggest that an increase in the number of sampled echoes beyond 6 does not affect AT PDFF quantification, whereas AT T2 * is considerably affected. Thus, a 20-echo gradient-echo acquisition enables a multiparametric analysis of both AT PDFF and T2 * and may therefore improve MR-based differentiation between white and brown fat.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:424-434. [ABSTRACT FROM AUTHOR]- Published
- 2019
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6. Ginsenoside rg3 reduces body weight by regulating fat content and browning in obese mice
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Ying Bai, Xin Fang, Sihua Gao, Jiacheng Zuo, Min Fu, Fangfang Mo, Qianqian Mu, Jing Hua, Dandan Zhao, and Xiaoshan Zhou
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Ginsenoside rg3 ,medicine.medical_specialty ,Blood lipids ,Adipose tissue ,Blood sugar ,White adipose tissue ,030226 pharmacology & pharmacy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Weight loss ,Internal medicine ,medicine ,Obesity ,lcsh:Miscellaneous systems and treatments ,030304 developmental biology ,PRDM16 ,0303 health sciences ,Chemistry ,lcsh:RZ409.7-999 ,Thermogenin ,Endocrinology ,Complementary and alternative medicine ,Ginsenoside ,White fat ,Browning ,medicine.symptom - Abstract
Objective To determine the effects of ginsenoside rg3 on the body weight of C57BL/6J obese mice and to investigate its underlying weight loss mechanisms with a focus on white fat browning-related factors. Methods Eight-week-old C57BL/6J male mice were fed a high-fat diet for 12 successive weeks to construct the obese model. C57BL/6J male mice were fed a standard chow diet to construct normal control group. After 8 weeks of intervention with ginsenoside rg3, the food intake, body weight, body fat mass, blood sugar, and lipid profiles of the mice in each group were detected. Hematoxylin and eosin (HE) staining was used to observe the histological morphology of the adipose tissues. Real-time polymerase chain reaction (RT-PCR) and Western blotting (WB) were applied to detect the gene and protein expression levels of peroxisome proliferators-activated receptor gama (PPARγ), Peroxisome proliferator-activated receptor-gamma coactivator -1alpha (PGC-1α), PR domain containing 16 (PRDM16), and uncoupling protein 1 (UCP-1). Results Compared to normal control group mice, the body weight, food intake, body fat composition, and blood lipid levels of model group mice increased significantly. After 8 weeks of intervention with ginsenoside rg3, body weight, body fat composition, food intake, and blood lipid profiles decreased. HE staining showed that ginsenoside rg3 can improve white adipocyte hypertrophy to a certain extent. RT-PCR and WB demonstrated that ginsenoside rg3 can increase the mRNA and protein expression levels of PPARγ, PGC-1α, PRDM16, and UCP-1 in the adipose tissues of obese mice. Conclusion The weight reduction effect of ginsenoside rg3 may be related to the promotion of white fat browning.
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- 2021
7. LncRNA Ctcflos orchestrates transcription and alternative splicing in thermogenic adipogenesis
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Bart Deplancke, Tobias Fromme, Peter Weber, Christoph Kiefer, Martin Klingenspor, Petra C. Schwalie, Yongguo Li, Anna Schießl, and Andrea Bast-Habersbrunner
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Gene isoform ,white fat ,adipocytes ,Adipose Tissue, White ,Brite Adipocytes ,Long Noncoding Rnas ,Prdm16 ,Splicing ,Ucp1-dependent Thermogenesis ,White adipose tissue ,Biology ,Biochemistry ,Article ,splicing ,Mice ,Adipose Tissue, Brown ,Gene expression ,Genetics ,brown adipose-tissue ,Animals ,brite adipocytes ,long noncoding RNAs ,gene ,Molecular Biology ,Gene ,mouse ,PRDM16 ,Adipogenesis ,Alternative splicing ,Thermogenesis ,Articles ,de-novo reconstruction ,Ucp1‐dependent thermogenesis ,RNA Biology ,Cell biology ,ddc ,cold-exposure ,Alternative Splicing ,Metabolism ,RNA splicing ,identification ,RNA, Long Noncoding ,long noncoding rna ,ucp1-dependent thermogenesis - Abstract
The recruitment of thermogenic brite adipocytes within white adipose tissue attenuates obesity and metabolic comorbidities, arousing interest in understanding the underlying regulatory mechanisms. The molecular network of brite adipogenesis, however, remains largely unresolved. In this light, long noncoding RNAs (lncRNAs) emerged as a versatile class of modulators that control many steps within the differentiation machinery. Leveraging the naturally varying propensities of different inbred mouse strains for white adipose tissue browning, we identify the nuclear lncRNA Ctcflos as a pivotal orchestrator of thermogenic gene expression during brite adipocyte differentiation. Mechanistically, Ctcflos acts as a pleiotropic regulator, being essential for the transcriptional recruitment of the early core thermogenic regulatory program and the modulation of alternative splicing to drive brite adipogenesis. This is showcased by Ctcflos‐regulated gene transcription and splicing of the key browning factor Prdm16 toward the isoform that is specific for the thermogenic gene program. Conclusively, our findings emphasize the mechanistic versatility of lncRNAs acting at several independent levels of gene expression for effective regulation of key differentiation factors to direct cell fate and function., LncRNA Ctcflos functions as an essential regulator in brite adipocyte development and thermogenesis through orchestration of transcriptional and post‐transcriptional alternative splicing programs. These include the modulation of transcript abundance and isoform profiles of Prdm16.
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- 2021
8. The brown fat secretome: metabolic functions beyond thermogenesis.
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Wang, Guo-Xiao, Zhao, Xu-Yun, and Lin, Jiandie D.
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BROWN adipose tissue , *ENERGY metabolism , *BODY temperature regulation , *UNCOUPLING proteins , *HOMEOSTASIS , *DRUG development - Abstract
Brown fat is highly active in fuel oxidation and dissipates chemical energy through uncoupling protein (UCP)1-mediated heat production. Activation of brown fat leads to increased energy expenditure, reduced adiposity, and lower plasma glucose and lipid levels, thus contributing to better homeostasis. Uncoupled respiration and thermogenesis have been considered to be responsible for the metabolic benefits of brown adipose tissue. Recent studies have demonstrated that brown adipocytes also secrete factors that act locally and systemically to influence fuel and energy metabolism. This review discusses the evidence supporting a thermogenesis-independent role of brown fat, particularly through its release of secreted factors, and their implications in physiology and therapeutic development. [ABSTRACT FROM AUTHOR]
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- 2015
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9. CD47 differentially regulates white and brown fat function
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Heather Norman-Burgdolf, Patrick G. Sullivan, Shuxia Wang, and Dong Li
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Male ,medicine.medical_specialty ,white fat ,QH301-705.5 ,Adipose Tissue, White ,Science ,CD47 Antigen ,030209 endocrinology & metabolism ,White adipose tissue ,Fatty Acids, Nonesterified ,Mitochondrion ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Adipose Tissue, Brown ,Internal medicine ,Brown adipose tissue ,medicine ,Animals ,Lipolysis ,Biology (General) ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Adipogenesis ,brown fat ,medicine.disease ,Obesity ,cd47 ,mitochondria ,medicine.anatomical_structure ,Endocrinology ,Gene Knockdown Techniques ,Lipogenesis ,Knockout mouse ,lipolysis ,Energy Metabolism ,General Agricultural and Biological Sciences ,Biomarkers ,Ex vivo ,Research Article - Abstract
Mechanisms that enhance energy expenditure are attractive therapeutic targets for obesity. Previously we have demonstrated that mice lacking cd47 are leaner, exhibit increased energy expenditure, and are protected against diet-induced obesity. In this study, we further defined the physiological role of cd47 deficiency in regulating mitochondrial function and energy expenditure in both white and brown adipose tissue. We observed that cd47 deficient mice (under normal chow diet) had comparable amount of white fat mass but reduced white adipocyte size as compared to wild-type mice. Subsequent ex vivo and in vitro studies suggest enhanced lipolysis, and not impaired lipogenesis or energy utilization, contributes to this phenotype. In contrast to white adipose tissue, there were no obvious morphological differences in brown adipose tissue between wild-type and knockout mice. However, mitochondria isolated from brown fat of cd47 deficient mice had significantly higher rates of free fatty acid-mediated uncoupling. This suggests that enhanced fuel availability via white adipose tissue lipolysis may perpetuate elevated brown adipose tissue energy expenditure and contributes to the lean phenotype observed in cd47 deficient mice., Summary: Under physiological conditions, CD47 differentially regulates white fat and brown fat function. Through a coordinated manner, altered fuel availability via white adipose tissue lipolysis may influence brown adipose tissue energy expenditure and then body weight management.
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- 2020
10. Dlgap1 negatively regulates browning of white fat cells through effects on cell proliferation and apoptosis
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Dongjun Liu, Yanhua Dong, Ju Zhang, Datong Lu, Hao Liang, Nan Yang, Jianfei Ma, Jie Yang, and Ming Cang
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0301 basic medicine ,White fat cell proliferation ,Endocrinology, Diabetes and Metabolism ,Adipose Tissue, White ,Clinical Biochemistry ,Proliferation ,Brown fat ,Adipocytes, White ,Blotting, Western ,Adipose tissue ,Apoptosis ,White adipose tissue ,Biology ,Dlgap1 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Endocrinology ,Adipose Tissue, Brown ,Gene expression ,Browning ,Animals ,lcsh:RC620-627 ,Cell Proliferation ,Cell growth ,Research ,Biochemistry (medical) ,Cell biology ,SAP90-PSD95 Associated Proteins ,White (mutation) ,lcsh:Nutritional diseases. Deficiency diseases ,030104 developmental biology ,Adipocytes, Brown ,White fat ,030217 neurology & neurosurgery - Abstract
Background Obesity is a metabolic imbalance characterized by excessive deposition of white fat. The browning of white fat can effectively treat obesity and related diseases. Although Dlgap1 (Discs, Large (Drosophila) Homolog-Associated Protein 1) is suspected to have an effect on this process, no empirical evidence is available. Methods To understand the role of Dlgap1, we cultured white and brown fat cells, then performed overexpression and knockout experiments. Results We found that Dlgap1 overexpression in brown adipocytes inhibits brown-fat-related gene expression, promotes white-fat-related genes, while also increasing brown-adipocyte proliferation and apoptosis. However, the gene overexpression has no effect on brown adipocyte maturation. Knocking out Dlgap1 in white fat cells promotes the expression and inhibition of brown-fat-related and white-fat-related genes, respectively. Additionally, the knockout inhibits white fat cell proliferation and apoptosis, while also promoting their maturation. Conclusions Dlgap1 negatively regulates the browning of white adipocytes by influencing cell proliferation and apoptosis.
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- 2020
11. The long noncoding RNA Blnc1 orchestrates homeostatic adipose tissue remodeling to preserve metabolic health
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Carey N. Lumeng, Tongyu Liu, Xiaoling Peng, Jennifer L. DelProposto, Xu-Yun Zhao, Siming Li, Cara E. Porsche, Jiandie D. Lin, and Lin Mi
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0301 basic medicine ,lcsh:Internal medicine ,Transgene ,Adipose Tissue, White ,Brown fat ,Whitening ,Adipose tissue ,White adipose tissue ,Biology ,Diet, High-Fat ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,lncRNA ,Adipose Tissue, Brown ,Fibrosis ,Adipocyte ,Cell Line, Tumor ,Conditional gene knockout ,medicine ,Animals ,Homeostasis ,Obesity ,lcsh:RC31-1245 ,Molecular Biology ,Cells, Cultured ,Inflammation ,Adipose tissue remodeling ,Cell Biology ,medicine.disease ,Cell biology ,DNA-Binding Proteins ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,White fat ,Cytokines ,Original Article ,RNA, Long Noncoding ,Energy Metabolism ,Thermogenesis ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
Objective Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their significance in adipose tissue metabolism and physiology has not been demonstrated in vivo. We previously identified Blnc1 as a conserved lncRNA regulator of brown and beige adipocyte differentiation. In this study, we investigated the physiological role of Blnc1 in thermogenesis, adipose remodeling and systemic metabolism. Methods We generated fat-specific Blnc1 transgenic and conditional knockout mouse strains and investigated how adipocyte Blnc1 levels are causally linked to key aspects of metabolic health following diet-induced obesity. We performed studies using cultured adipocytes to establish cell-autonomous role of Blnc1 in regulating adipocyte gene programs. Results Blnc1 is highly induced in both brown and white fats from obese mice. Fat-specific inactivation of Blnc1 impairs cold-induced thermogenesis and browning and exacerbates obesity-associated brown fat whitening, adipose tissue inflammation and fibrosis, leading to more severe insulin resistance and hepatic steatosis. On the contrary, transgenic expression of Blnc1 in adipose tissue elicits the opposite and beneficial metabolic effects, supporting a critical role of Blnc1 in driving adipose adaptation and homeostatic remodeling during obesity. Mechanistically, Blnc1 cell-autonomously attenuates proinflammatory cytokine signaling and promotes fuel storage in adipocytes through its protein partner Zbtb7b. Conclusions This study illustrates a surprisingly pleiotropic and dominant role of lncRNA in driving adaptive adipose tissue remodeling and preserving metabolic health., Highlights • Adipocyte-specific Blnc1 inactivation accelerates BAT whitening and impairs healthy WAT expansion. • Blnc1 transgenic mice are protected from diet-induced metabolic disorders. • Blnc1 attenuates adipose tissue inflammation and preserves metabolic health in obesity. • Blnc1 suppresses NF-kB signaling and TNFα-induced cytokine/chemokine release by adipocytes.
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- 2018
12. Brown versus White Adipose Tissue: A Mini-Review.
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Saely, Christoph H., Geiger, Kathrin, and Drexel, Heinz
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GERONTOLOGY research , *BROWN adipose tissue , *AGING , *TRIGLYCERIDES , *METABOLIC disorders - Abstract
Background: Brown adipose tissue (BAT) is abundant in small mammals and in newborns and helps them to survive cold temperatures. In adults, it had long been considered to be absent or at least of no relevance. Recent investigations, however, have fuelled interest in adult BAT. Objective: We aimed at (1) summarizing structural and physiological characteristics of BAT versus white adipose tissue (WAT); (2) discussing the development of the two adipose tissue types; (3) reviewing the data available from human studies on BAT, and (4) discussing the impact of aging. Methods: We summarize recent descriptions of BAT and WAT based on the original literature and reviews in the field, with emphasis on human BAT. Results: WAT and BAT have essentially antagonistic functions: WAT stores excess energy as triglycerides and BAT is specialized in the dissipation of energy through the production of heat. Considerable amounts of BAT are present in a substantial proportion of adult humans and relatively high quantities of BAT are associated with lower body weight. With increasing age, BAT decreases and body weight increases. Conclusions: Although the available cross-sectional data do not allow definite conclusions to be drawn concerning a causal relationship between loss of BAT and increasing body weight with advancing age or obesity-related metabolic disorders of older age, stimulation of BAT appears to be an attractive novel candidate target for the treatment of age-related obesity. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2011
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13. Thermogenic Capacity of Human White-Fat: The Actual Picture†
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Marinos Metaxas, Alexandros Georgakopoulos, Yiannis Koutedakis, John Koutsikos, Panagiotis Georgoulias, Argyro Krase, Roberto Vettor, Tiago Sotto Mayor, Marco Rossato, Eleni Karachaliou, Andreas D. Flouris, Athanasios Z. Jamurtas, Marnie Granzotto, Leonidas G. Ioannou, Paraskevi Gkiata, Andres E. Carrillo, Sofia Chatziioannou, Konstantinos Athanasiou, Petros C. Dinas, George S. Metsios, and Eleni Nintou
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medicine.medical_specialty ,exercise ,Normal diet ,white fat ,business.industry ,uncoupling protein 1 ,cold exposure ,Cold exposure ,lcsh:A ,White adipose tissue ,Thermogenin ,Confidence interval ,Environmental temperature ,Endocrinology ,thermogenicity ,Internal medicine ,Medicine ,White Adipocytes ,Animal studies ,lcsh:General Works ,business - Abstract
AIM: Cold exposure and exercise may increase thermogenic capacity of white adipose tissue (WAT), which could subsequently enhance energy expenditure and body weight loss. We aimed to identify possible alterations in uncoupling protein 1 (UCP1)—the main biomarker of thermogenic activation—in human WAT due to both cold exposure and exercise, as well as the link between environmental temperature and thermogenic capacity of human WAT. MATERIAL & METHOD: We conducted four human experimental studies and two systematic reviews and meta-analyses—PROSPERO registration CRD42019120116, CRD42019120213. RESULTS: UCP1 mRNA was higher in winter than in summer [t(30) = 2.232, p = 0.03] in human WAT and our meta-analysis showed a main effect of cold exposure on human UCP1 mRNA [standard mean difference (Std-md) = 1.81, confidence interval (CI) = 0.50–3.13, p = 0.007]. However, UCP1 mRNA/protein expressions displayed no associations with %fat mass or BMI (p > 0.05, Cohen’s f2 < 0.20). Both a 2-hour cooling and a non-cooling protocol preceding the positron emission tomography/computed tomography (PET/CT) measurements revealed no association between environmental temperature and standardised uptake value (SUVmax) of human WAT, as well as no mean differences in SUVmax-WAT-activity between winter and summer. An 8-week exercise program had no effect on UCP1 of human WAT or on body composition. Our meta-analysis also revealed: (a) no effect of chronic exercise on human UCP1 mRNA, (b) a main effect of chronic exercise on UCP1 protein concentrations (Std-md = 0.59, CI = 0.03–1.16, p = 0.04) and UCP1 mRNA (Std-md = 1.76, CI = 0.48–3.04, p = 0.007) in WAT of normal diet animals, c) a main effect of chronic exercise on UCP1 mRNA (Std-md = 2.94, CI = 0.24–5.65, p = 0.03) and UCP1 protein concentrations (Std-md = 2.06, CI = 0.07–4.05, p = 0.04) of high-fat diet animals. CONCLUSIONS: Cold exposure represents a main stimulus for increased thermogenic capacity in human white adipocytes; however, this may have no impact on body weight loss. Chronic exercise may represent no major stimulus for UCP1 induced in human white adipocytes, while in animals it increases UCP1 gene independently of their diet. Therefore, evidence from animal studies regarding UCP1 gene activation in white adipocytes may not be applicable in humans. Finally, the identification of human WAT thermogenic capacity via PET/CT examination may be optimal with both a cooling and a non-cooling protocol.
- Published
- 2019
14. Interscapular and Perivascular Brown Adipose Tissue Respond Differently to a Short-Term High-Fat Diet
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Peter Aldiss, Helen Budge, Amanda K. Miles, David J. Boocock, Michael E. Symonds, Ian Bloor, Francis J. P. Ebling, and Jo E. Lewis
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Male ,medicine.medical_specialty ,Nucleosome assembly ,white fat ,proteome ,Adipose tissue ,Peroxisome proliferator-activated receptor ,Down-Regulation ,lcsh:TX341-641 ,Histone exchange ,White adipose tissue ,Biology ,Diet, High-Fat ,Article ,Drug Administration Schedule ,Rats, Sprague-Dawley ,Mice ,Adipose Tissue, Brown ,Internal medicine ,nutrient excess ,Brown adipose tissue ,medicine ,Animals ,chemistry.chemical_classification ,molecular_biology ,brown fat ,Lipid metabolism ,Thermogenesis ,Dietary Fats ,Rats ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Gene Expression Regulation ,Body Composition ,medicine.symptom ,Insulin Resistance ,Weight gain ,lcsh:Nutrition. Foods and food supply - Abstract
Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n=12) were fed either a standard (10% fat, n=6) or high fat diet (HFD: 45% fat, n=6) for 72h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72h induced rapid weight gain (c. 2.6%) and reduced serum non-esterified fatty acids (NEFA) with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and peroxisome proliferator-activated receptor (PPAR) signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g., Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.
- Published
- 2019
15. Exercise training-induced effects on the abdominal subcutaneous adipose tissue phenotype in humans with obesity
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Ellen E. Blaak, Johan W. E. Jocken, Matthijs K. C. Hesselink, Bram Brouwers, Gijs H. Goossens, Patrick Schrauwen, Karianna F. Teunissen-Beekman, Rudi Stinkens, Marleen A. van Baak, Promovendi NTM, Humane Biologie, RS: NUTRIM - R2 - Liver and digestive health, RS: NUTRIM - R1 - Metabolic Syndrome, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, and Nutrition and Movement Sciences
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,obesity ,Physiology ,Lipolysis ,PGC-1-ALPHA ,Adipose tissue ,030209 endocrinology & metabolism ,White adipose tissue ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Gene expression ,Adipocytes ,Medicine ,Humans ,IMPROVES INSULIN SENSITIVITY ,WHITE FAT ,BROWN ,PLASMA-LEVELS ,Exercise ,protein expression ,Aged ,GENE-EXPRESSION ,Messenger RNA ,OXIDATIVE CAPACITY ,business.industry ,Skeletal muscle ,Resistance Training ,MITOCHONDRIAL BIOGENESIS ,Middle Aged ,medicine.disease ,Obesity ,Phenotype ,Subcutaneous Fat, Abdominal ,abdominal subcutaneous adipose tissue ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Mitochondrial biogenesis ,gene expression ,SKELETAL-MUSCLE ,business ,MESSENGER-RNA ,exercise training - Abstract
Rodent studies have indicated that physical exercise may improve adipose tissue function. We investigated the effects of a 12-wk supervised, progressive exercise training program on adipocyte morphology and abdominal subcutaneous adipose tissue function in metabolically well-phenotyped subjects with obesity. Men with obesity ( n = 21) participated in a 12-wk supervised, progressive, combined exercise training program consisting of aerobic exercise (30 min at 70% of maximal power output 2 times/wk) and resistance exercise (3 × 10 repetitions at 60% of 1 repeated maximum 1 time/wk), with adjustment of exercise intensity every 4 wk. At baseline and after intervention, abdominal subcutaneous adipose tissue biopsies were collected to determine 1) adipocyte morphology, 2) gene expression of markers for lipolysis, inflammation, browning, adipokines, and mitochondrial biogenesis/function, 3) protein expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes, and 4) ex vivo basal and β2-adrenergic stimulated lipolysis. The exercise training program, which increased maximal aerobic capacity ( P < 0.001) and muscle strength ( P < 0.001), slightly reduced adipose tissue mass (~0.7 kg, P = 0.021) but did not affect abdominal subcutaneous adipocyte size ( P = 0.744), adipose tissue gene expression of markers for mitochondrial biogenesis and function, browning, lipolysis, inflammation and adipokines, total OXPHOS protein content ( P = 0.789), or β2-adrenergic sensitivity of lipolysis ( P = 0.555). A 12-wk supervised, progressive exercise training program did not alter abdominal subcutaneous adipocyte morphology and adipose tissue gene/protein expression of markers related to adipose tissue function or β2-adrenergic sensitivity of lipolysis in male subjects with obesity.NEW & NOTEWORTHY Studies that investigated the effects of exercise training on adipose tissue function in well-phenotyped humans are scarce. We demonstrate that 12 wk of supervised exercise training improved physical fitness and peripheral insulin sensitivity but did not alter abdominal subcutaneous adipocyte morphology, adipose tissue gene and protein expression of markers related to adipose tissue function, or β2-adrenergic receptor-mediated lipolysis in men with obesity. A prolonged and/or more intense training program may be required to improve human adipose tissue function.
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- 2018
16. New Physiological Aspects of Brown Adipose Tissue
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Trayhurn, Paul and Arch, Jonathan R. S.
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- 2014
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17. Brown and beige adipose tissues: phenotype and metabolic potential in mice and men
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Denis Richard, Wouter D. van Marken Lichtenbelt, and Kanta Chechi
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0301 basic medicine ,medicine.medical_specialty ,Bodily Secretions ,FATTY-ACID OXIDATION ,Nonshivering thermogenesis ,Physiology ,Adipose tissue ,White adipose tissue ,Review ,Diet induced thermogenesis ,Biology ,ADULT HUMANS ,03 medical and health sciences ,UNCOUPLING PROTEIN-1 GENE ,Metabolic potential ,Adipose Tissue, Brown ,Physiology (medical) ,Internal medicine ,medicine ,Glucose homeostasis ,Animals ,Humans ,WHITE FAT ,CENTRAL SENSORY CIRCUITS ,sympathetic nervous system ,ENERGY-EXPENDITURE ,brown fat ,Thermogenesis ,Adipose Tissue, Beige ,NERVOUS-SYSTEM OUTFLOW ,Phenotype ,NONSHIVERING THERMOGENESIS ,DIET-INDUCED THERMOGENESIS ,030104 developmental biology ,Endocrinology ,beige fat ,GLUCOSE-HOMEOSTASIS ,Energy Metabolism - Abstract
With the recent rediscovery of brown fat in adult humans, our outlook on adipose tissue biology has undergone a paradigm shift. While we attempt to identify, recruit, and activate classic brown fat stores in humans, identification of beige fat has also raised the possibility of browning our white fat stores. Whether such transformation of human white fat depots can be achieved to enhance the whole body oxidative potential remains to be seen. Evidence to date, however, largely points toward a major oxidative role only for classic brown fat depots, at least in rodents. White fat stores seem to provide the main fuel for sustaining thermogenesis via lipolysis. Interestingly, molecular markers consistent with both classic brown and beige fat identity can be observed in human supraclavicular depot, thereby complicating the discussion on beige fat in humans. Here, we review the recent advances made in our understanding of brown and beige fat in humans and mice. We further provide an overview of their plausible physiological relevance to whole body energy metabolism.
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- 2017
18. Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review
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Javier Ruiz-Ojeda, Francisco, Iris Ruperez, Azahara, Gomez-Llorente, Carolina, Gil, Angel, Maria Aguilera, Concepcion, [Javier Ruiz-Ojeda, Francisco] Univ Granada, Dept Biochem & Mol Biol 2, Inst Nutr & Food Technol Jose Mataix, Sch Pharm,Ctr Biomed Res, Campus Cartuja S-N,Ave Conocimiento S-N,18016, E-18071 Granada, Spain, [Iris Ruperez, Azahara] Univ Granada, Dept Biochem & Mol Biol 2, Inst Nutr & Food Technol Jose Mataix, Sch Pharm,Ctr Biomed Res, Campus Cartuja S-N,Ave Conocimiento S-N,18016, E-18071 Granada, Spain, [Gomez-Llorente, Carolina] Univ Granada, Dept Biochem & Mol Biol 2, Inst Nutr & Food Technol Jose Mataix, Sch Pharm,Ctr Biomed Res, Campus Cartuja S-N,Ave Conocimiento S-N,18016, E-18071 Granada, Spain, [Gil, Angel] Univ Granada, Dept Biochem & Mol Biol 2, Inst Nutr & Food Technol Jose Mataix, Sch Pharm,Ctr Biomed Res, Campus Cartuja S-N,Ave Conocimiento S-N,18016, E-18071 Granada, Spain, [Maria Aguilera, Concepcion] Univ Granada, Dept Biochem & Mol Biol 2, Inst Nutr & Food Technol Jose Mataix, Sch Pharm,Ctr Biomed Res, Campus Cartuja S-N,Ave Conocimiento S-N,18016, E-18071 Granada, Spain, [Javier Ruiz-Ojeda, Francisco] Univ Granada, Inst Invest Biosanitaria Ibs, Complejo Hosp Univ Granada, E-18014 Granada, Spain, [Gomez-Llorente, Carolina] Univ Granada, Inst Invest Biosanitaria Ibs, Complejo Hosp Univ Granada, E-18014 Granada, Spain, [Gil, Angel] Univ Granada, Inst Invest Biosanitaria Ibs, Complejo Hosp Univ Granada, E-18014 Granada, Spain, [Maria Aguilera, Concepcion] Univ Granada, Inst Invest Biosanitaria Ibs, Complejo Hosp Univ Granada, E-18014 Granada, Spain, [Gomez-Llorente, Carolina] Inst Salud Carlos III, CIBEROBN Physiopathol Obes & Nutr CB12 03 30038, Madrid 28029, Spain, [Gil, Angel] Inst Salud Carlos III, CIBEROBN Physiopathol Obes & Nutr CB12 03 30038, Madrid 28029, Spain, [Maria Aguilera, Concepcion] Inst Salud Carlos III, CIBEROBN Physiopathol Obes & Nutr CB12 03 30038, Madrid 28029, Spain, Junta de Andalucia, Junta de Andalucia (Secretaria General de Universidades, Investigacion y Tecnologia), Junta de Andalucia (Consejeria de Economia, Innovacion y Ciencia), Junta de Andalucia (Implicaciones biologicas de genes de las vias de senalizacion de la insulina, inflamacion y de la matriz extracelular en cultivos de celulas madre mesenquimales de tejido adiposo humano), and Ministry of Education and Science of the Spanish Government
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cell culture techniques ,obesity ,adipocytes ,in vitro techniques ,brown adipose tissue ,Inhibits adipocyte differentiation ,Brown adipose-tissue ,cell differentiation ,white adipose tissue ,Human pre-adipocytes ,3t3-l1 cells ,Morphogenetic protein 4 ,beige cells ,White fat ,Human preadipocytes ,Gene-expression ,Mesenchymal stem-cells ,Porcine preadipocytes - Abstract
Over the last several years, the increasing prevalence of obesity has favored an intense study of adipose tissue biology and the precise mechanisms involved in adipocyte differentiation and adipogenesis. Adipocyte commitment and differentiation are complex processes, which can be investigated thanks to the development of diverse in vitro cell models and molecular biology techniques that allow for a better understanding of adipogenesis and adipocyte dysfunction associated with obesity. The aim of the present work was to update the different animal and human cell culture models available for studying the in vitro adipogenic differentiation process related to obesity and its co-morbidities. The main characteristics, new protocols, and applications of the cell models used to study the adipogenesis in the last five years have been extensively revised. Moreover, we depict co-cultures and three-dimensional cultures, given their utility to understand the connections between adipocytes and their surrounding cells in adipose tissue.
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- 2016
19. Low brown adipose tissue activity in endurance-trained compared with lean sedentary men
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Joris Hoeks, Evie P.M. Broeders, A A J J van der Lans, W.D. van Marken Lichtenbelt, Emmani B.M. Nascimento, Maarten J. Vosselman, Felix M. Mottaghy, Hannah Pallubinsky, Patrick Schrauwen, Boudewijn Brans, Humane Biologie, MUMC+: DA BV Medische staf (6), Beeldvorming, RS: NUTRIM - R1 - Metabolic Syndrome, and RS: NUTRIM - HB/BW section B
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Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Adipose tissue ,THERMOGENESIS ,EXERCISE ,White adipose tissue ,ADULT HUMANS ,IRISIN ,RATS ,Adipose Tissue, Brown ,Thinness ,Endurance training ,Fluorodeoxyglucose F18 ,Internal medicine ,Brown adipose tissue ,Myokine ,Medicine ,Humans ,MESSENGER-RNA EXPRESSION ,WHITE FAT ,Muscle, Skeletal ,COLD ,GENE-EXPRESSION ,Nutrition and Dietetics ,business.industry ,Interleukin-6 ,Skeletal muscle ,MUSCLE ,FNDC5 ,Fibronectins ,Cold Temperature ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,Athletes ,Positron-Emission Tomography ,Physical Endurance ,Radiopharmaceuticals ,Sedentary Behavior ,business ,Tomography, X-Ray Computed ,Thermogenesis ,Biomarkers - Abstract
BACKGROUND/OBJECTIVES: It has now been unequivocally demonstrated that humans possess functional brown adipose tissue (BAT) and that human BAT can be recruited upon chronic cold stimulation. Recruitment of BAT has been postulated as a potential strategy to counteract the current global obesity epidemic. Recently, it was shown in rodents that endurance exercise training could stimulate the recruitment of brown-like adipocytes within white adipose tissue (WAT) via exercise-induced myokines such as irisin (the cleaved circulating product of the type 1 membrane protein FNDC5) and interleukin-6 (IL-6). Our objective was to test whether endurance-trained athletes had increased cold-stimulated BAT activity and browning of subcutaneous WAT compared with lean sedentary males. SUBJECTS/METHODS: Twelve endurance-trained athletes and 12 lean sedentary males were measured during 2 h of mild cold exposure to determine cold-induced BAT activity via [(18)F]fluorodeoxyglucose-positron emission tomography-computed tomography ([(18)F]FDG-PET-CT) scanning. Skeletal muscle FNDC5 expression, as well as plasma irisin and IL-6 levels were determined. In addition, a subcutaneous abdominal WAT biopsy was taken to measure gene expression of several markers for browning of WAT. RESULTS: Cold-induced BAT activity was significantly lower in athletes, and no differences in gene expression of classical brown and beige adipocyte markers were detected in subcutaneous WAT between the groups. As expected, mRNA expression of FNDC5 in skeletal muscle was significantly higher in endurance athletes but plasma irisin and Il-6 levels were similar in both groups. CONCLUSIONS: These results indicate that chronic endurance exercise is not associated with brown and beige adipocyte recruitment; in fact endurance training appears to be linked to lower the metabolic activity of BAT in humans.
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- 2015
20. Transcriptional fingerprinting of 'browning' white fat identifies NRG4 as a novel adipokine
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Mark Christian
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medicine.medical_specialty ,Histology ,white fat ,Brown fat ,Adipokine ,Adipose tissue ,030209 endocrinology & metabolism ,White adipose tissue ,Biology ,adipocyte ,neuregulin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adipocyte ,Internal medicine ,Commentaries ,Brown adipose tissue ,medicine ,education ,030304 developmental biology ,PRDM16 ,0303 health sciences ,Neuregulin-4 ,education.field_of_study ,adipokine ,Cell Biology ,thermogenesis ,BRITE adipocyte ,beige adipocyte ,Nrg4 ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Thermogenesis ,metabolism - Abstract
Brown adipocytes help to maintain body temperature by the expression of a unique set of genes that facilitate cellular metabolic events including uncoupling protein 1-dependent thermogenesis. The dissipation of energy in brown adipose tissue (BAT) is in stark contrast to white adipose tissue (WAT) which is the body’s primary site of energy storage. However, adipose tissue is highly dynamic and upon cold exposure profound changes occur in WAT resulting in a BAT-like phenotype due to the presence of brown-in-white (BRITE) adipocytes. In our recent report, transcription profiling was used to identify the gene expression changes that underlie the browning process as well as the intrinsic differences between BAT and WAT. Neuregulin 4 was categorized as a cold-induced BAT gene encoding an adipokine that signals between adipocytes and nerve cells and likely to have a role in increasing adipose tissue innervation in response to cold.
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- 2014
21. Increased Oxygen Consumption in Human Adipose Tissue From the 'Brown Adipose Tissue' Region
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Patrick Schrauwen, Joris Hoeks, Guy H. E. J. Vijgen, Nicole D. Bouvy, Gert Schaart, Lauren M. Sparks, Wouter D. van Marken Lichtenbelt, Surgery, Humane Biologie, Nutrition and Movement Sciences, and RS: NUTRIM - R1 - Metabolic Syndrome
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Endocrinology, Diabetes and Metabolism ,Glucose uptake ,Clinical Biochemistry ,Adipose tissue ,White adipose tissue ,Multimodal Imaging ,Biochemistry ,Ion Channels ,Cohort Studies ,Endocrinology ,Adipose Tissue, Brown ,Brown adipose tissue ,Prospective Studies ,Uncoupling Protein 1 ,Adiposity ,medicine.diagnostic_test ,Thyroid ,Age Factors ,Middle Aged ,INSULIN ,Up-Regulation ,medicine.anatomical_structure ,RESPIRATION ,SKELETAL-MUSCLE ,Adult ,Shoulder ,medicine.medical_specialty ,MITOCHONDRIAL DYSFUNCTION ,Subcutaneous Fat ,THERMOGENESIS ,Context (language use) ,Biology ,Mitochondrial Proteins ,Young Adult ,Oxygen Consumption ,Fluorodeoxyglucose F18 ,Internal medicine ,Biopsy ,medicine ,Humans ,WHITE FAT ,COLD ,Aged ,Uncoupling Agents ,Biochemistry (medical) ,ENERGY-EXPENDITURE ,Positron-Emission Tomography ,Basal Metabolism ,Radiopharmaceuticals ,Tomography, X-Ray Computed ,Thermogenesis ,RESPONSES - Abstract
Context: Since the discovery of functional brown adipose tissue (BAT) in adult humans, there has been a renewed interest in the physiology of human BAT. Imaging studies from our laboratory and others have shown increased glucose uptake in adipose tissue regions assumed to be BAT in humans. We have also shown that human BAT from the supraclavicular (SCV) region is positive for uncoupling protein-1. To date, however, the oxidative capacity of this adipose tissue (AT) depot has not been characterized in humans.Objective: We hypothesize that oxidative capacity is increased in the AT of the SCV region known to contain human BAT.Design: This was an observational prospective cohort study.Setting: The study was conducted at a referral center.Patients: Participants were 13 patients for whom thyroid gland surgery was indicated.Main Outcome Measure: Basal cellular oxygen consumption in human AT biopsy samples from the SCV region, known to be [F-18]fluorodeoxyglucose positron emission tomography-computed tomography-positive, was compared with the cellular oxygen consumption in subcutaneous white adipose tissue (WAT) from the same region of the same subject.Results: We show for the first time that AT from the human BAT region displays increased oxygen consumption (P Conclusions: These results suggest that human adipose tissue from the BAT region can be distinguished from subcutaneous WAT by a higher basal oxidative capacity. Additional studies are warranted to further elucidate the metabolic and bioenergetic characteristics of this AT depot in humans.
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- 2013
22. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality
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Folli, Franco, Boon, Mariëtte R., van den Berg, Sjoerd A. A., Wang, Yanan, van den Bossche, Jan, Karkampouna, Sofia, Bauwens, Matthias, De Saint-Hubert, Marijke, van der Horst, Geertje, Vukičević, Slobodan, de Winther, Menno P. J., Havekes, Louis M., Jukema, J. Wouter, Tamsma, Jouke T., van der Pluijm, Gabri, van Dijk, Ko Willems, Rensen, Patrick C. N., ACS - Amsterdam Cardiovascular Sciences, AII - Amsterdam institute for Infection and Immunity, Medical Biochemistry, MUMC+: DA BV Medische staf (6), Genetica & Celbiologie, RS: NUTRIM - R1 - Metabolic Syndrome, and Beeldvorming
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Male ,Sympathetic nervous system ,CD36 ,BONE MORPHOGENETIC PROTEIN-7 ,Bone Morphogenetic Protein 7 ,Adipose tissue ,Biomedical Innovation ,White adipose tissue ,MOUSE ,Mice ,Absorptiometry, Photon ,Adipose Tissue, Brown ,Life ,Brown adipose tissue ,Uncoupling protein ,Multidisciplinary ,biology ,Temperature ,MUSCLE ,ADIPOCYTES ,medicine.anatomical_structure ,Health ,embryonic structures ,Medicine ,EELS - Earth, Environmental and Life Sciences ,MHR - Metabolic Health Research ,Healthy Living ,Research Article ,medicine.medical_specialty ,animal structures ,Science ,THERMOGENESIS ,Diet, High-Fat ,Internal medicine ,medicine ,Lipolysis ,Animals ,WHITE FAT ,CELL ,Obesity ,IDENTIFICATION ,Mice, Inbred C57BL ,Endocrinology ,ATHEROSCLEROSIS ,Adipocytes ,Diet ,Dyslipidemia ,Lipids ,Macrophages ,Oxidation ,biology.protein ,Energy Metabolism ,Thermogenesis - Abstract
BACKGROUND/AIMS: Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity. METHODS AND RESULTS: High-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21 degrees C or 28 degrees C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21 degrees C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28 degrees C. Additionally, BMP7 resulted in extensive 'browning' of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia. CONCLUSION: Together, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to combat obesity and associated disorders.
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- 2013
23. Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
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Li Ye, Joris Hoeks, Patrick Schrauwen, Jang Hyun Choi, Kexin Huang, Gert Schaart, Jun Wu, Hua Tu, Pirjo Nuutila, Kirsi A. Virtanen, Lauren M. Sparks, An Hoa Giang, Bruce M. Spiegelman, Pontus Boström, Sven Enerbäck, Wouter D. van Marken Lichtenbelt, Melin J. Khandekar, Humane Biologie, Nutrition and Movement Sciences, and RS: NUTRIM - R1 - Metabolic Syndrome
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medicine.medical_specialty ,Adipocytes, White ,Adipose tissue ,030209 endocrinology & metabolism ,White adipose tissue ,Cell Separation ,Biology ,ta3111 ,General Biochemistry, Genetics and Molecular Biology ,Article ,Ion Channels ,ACTIVATION ,Mitochondrial Proteins ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Adipose Tissue, Brown ,Internal medicine ,Brown adipose tissue ,medicine ,Adipocytes ,Uncoupling protein ,Animals ,Humans ,WHITE FAT ,Progenitor cell ,IN-VIVO ,Uncoupling Protein 1 ,030304 developmental biology ,PRDM16 ,0303 health sciences ,IDENTIFICATION ,PROGENITORS ,BROWN ADIPOSE-TISSUE ,Biochemistry, Genetics and Molecular Biology(all) ,INDUCTION ,Gene Expression Profiling ,ta1182 ,ta3121 ,FNDC5 ,Thermogenin ,medicine.anatomical_structure ,Endocrinology ,OBESITY ,SKELETAL-MUSCLE ,TRANSCRIPTIONAL CONTROL - Abstract
SummaryBrown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of “beige” cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but, like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we provide evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes. These data provide a foundation for studying this mammalian cell type with therapeutic potential.PaperClip
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