Two Faces of White Adipose Tissue with Heterogeneous Adipogenic Progenitors

Chronic energy surplus increases body fat, leading to obesity. Since obesity is closely associated with most metabolic complications, pathophysiological roles of adipose tissue in obesity have been intensively studied. White adipose tissue is largely divided into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). These two white adipose tissues are similar in their appearance and lipid storage functions. Nonetheless, emerging evidence has suggested that SAT and VAT have different characteristics and functional roles in metabolic regulation. It is likely that there are intrinsic differences between VAT and SAT. In diet-induced obese animal models, it has been reported that adipogenic progenitors in VAT rapidly proliferate and differentiate into adipocytes. In obesity, VAT exhibits elevated inflammatory responses, which are less prevalent in SAT. On the other hand, SAT has metabolically beneficial effects. In this review, we introduce recent studies that focus on cellular and molecular components modulating adipogenesis and immune responses in SAT and VAT. Given that these two fat depots show different functions and characteristics depending on the nutritional status, it is feasible to postulate that SAT and VAT have different developmental origins with distinct adipogenic progenitors, which would be a key determining factor for the response and accommodation to metabolic input for energy homeostasis.

[1]  Sunhye Shin,et al.  Adipose stem cells in obesity: challenges and opportunities , 2020, Bioscience reports.

[2]  Jiyoung Park,et al.  Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity , 2019, Genes & development.

[3]  J. B. Kim,et al.  During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization , 2019, Molecular and Cellular Biology.

[4]  Jason K. Kim,et al.  GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity , 2019, Proceedings of the National Academy of Sciences.

[5]  C. Benoist,et al.  Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors , 2019, Science Immunology.

[6]  Ivona Percec,et al.  Identification of a mesenchymal progenitor cell hierarchy in adipose tissue , 2019, Science.

[7]  Jeu Park,et al.  Effects of Three Thiazolidinediones on Metabolic Regulation and Cold-Induced Thermogenesis , 2018, Molecules and cells.

[8]  G. Hon,et al.  Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice , 2018, eLife.

[9]  R. Pique-Regi,et al.  Deconstructing Adipogenesis Induced by β3-Adrenergic Receptor Activation with Single-Cell Expression Profiling. , 2018, Cell metabolism.

[10]  M. Mingler,et al.  Eosinophils support adipocyte maturation and promote glucose tolerance in obesity , 2018, Scientific Reports.

[11]  Petra C. Schwalie,et al.  A stromal cell population that inhibits adipogenesis in mammalian fat depots , 2018, Nature.

[12]  S. Kajimura,et al.  The Common and Distinct Features of Brown and Beige Adipocytes , 2018, Trends in Endocrinology & Metabolism.

[13]  J. Ching,et al.  Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation , 2017, Nature Communications.

[14]  M. Blüher,et al.  The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue , 2017, Nature Medicine.

[15]  K. Clément,et al.  A PDGFRα-Mediated Switch toward CD9high Adipocyte Progenitors Controls Obesity-Induced Adipose Tissue Fibrosis. , 2017, Cell metabolism.

[16]  Y. Lee,et al.  Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity , 2017, Diabetes.

[17]  J. B. Kim,et al.  Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders , 2016, Front. Endocrinol..

[18]  S. Shoelson,et al.  Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity. , 2016, Cell metabolism.

[19]  Q. Tang,et al.  BMP4 mediates the interplay between adipogenesis and angiogenesis during expansion of subcutaneous white adipose tissue. , 2016, Journal of molecular cell biology.

[20]  Manna Zhang,et al.  Eosinophils Reduce Chronic Inflammation in Adipose Tissue by Secreting Th2 Cytokines and Promoting M2 Macrophages Polarization , 2015, International journal of endocrinology.

[21]  Rana K. Gupta,et al.  Visceral Adipose Tissue Mesothelial Cells: Living on the Edge or Just Taking Up Space? , 2015, Trends in Endocrinology & Metabolism.

[22]  J. Wren,et al.  PDGFRα signaling drives adipose tissue fibrosis by targeting progenitor cell plasticity , 2015, Genes & development.

[23]  Chun-Yan Lim,et al.  Lipid-Overloaded Enlarged Adipocytes Provoke Insulin Resistance Independent of Inflammation , 2015, Molecular and Cellular Biology.

[24]  J. Seong,et al.  Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon‐like peptide 1 in diet‐induced obesity , 2015, The FASEB Journal.

[25]  M. Rodeheffer,et al.  Rapid Depot-Specific Activation of Adipocyte Precursor Cells at the Onset of Obesity , 2015, Nature Cell Biology.

[26]  Benjamin R. Herbert,et al.  Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice , 2014, Diabetologia.

[27]  E. Ravussin,et al.  Metabolically healthy and unhealthy obese – the 2013 Stock Conference report , 2014, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[28]  Y. Lee,et al.  Macrophage HIF-2α Ameliorates Adipose Tissue Inflammation and Insulin Resistance in Obesity , 2014, Diabetes.

[29]  Jung-whan Kim,et al.  Increased Adipocyte O2 Consumption Triggers HIF-1α, Causing Inflammation and Insulin Resistance in Obesity , 2014, Cell.

[30]  E. Engleman,et al.  B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance , 2014, Cellular and Molecular Life Sciences.

[31]  N. Hastie,et al.  Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source , 2014, Nature Cell Biology.

[32]  Haiming Cao Adipocytokines in obesity and metabolic disease. , 2014, The Journal of endocrinology.

[33]  K. Clément,et al.  Fibrosis and adipose tissue dysfunction. , 2013, Cell metabolism.

[34]  J. Granneman,et al.  Identification of an adipogenic niche for adipose tissue remodeling and restoration. , 2013, Cell metabolism.

[35]  P. Scherer,et al.  Tracking adipogenesis during white adipose tissue development, expansion and regeneration , 2013, Nature Medicine.

[36]  Dorothy D. Sears,et al.  Macrophage Glucose-6-Phosphate Dehydrogenase Stimulates Proinflammatory Responses with Oxidative Stress , 2013, Molecular and Cellular Biology.

[37]  R. Seong,et al.  A Novel Function of Adipocytes in Lipid Antigen Presentation to iNKT Cells , 2012, Molecular and Cellular Biology.

[38]  S. Balk,et al.  Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. , 2012, Immunity.

[39]  D. McClain,et al.  MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity , 2012, Nature Medicine.

[40]  M. Lane,et al.  Adipogenesis: from stem cell to adipocyte. , 2012, Annual review of biochemistry.

[41]  Liu Yang,et al.  Short Term High Fat Diet Challenge Promotes Alternative Macrophage Polarization in Adipose Tissue via Natural Killer T Cells and Interleukin-4* , 2012, The Journal of Biological Chemistry.

[42]  Vrajesh V. Parekh,et al.  Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice , 2012, Proceedings of the National Academy of Sciences.

[43]  Yun-Hee Lee,et al.  In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high-fat feeding. , 2012, Cell metabolism.

[44]  Guido Gerken,et al.  The interaction of hepatic lipid and glucose metabolism in liver diseases. , 2012, Journal of hepatology.

[45]  S. Woods,et al.  Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: Role of hepatic triglyceride storage , 2011, Physiology & Behavior.

[46]  R. Schwendener,et al.  Inflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance , 2011, Diabetes.

[47]  Daniel Hidalgo,et al.  Identification and analysis of mouse erythroid progenitors using the CD71/TER119 flow-cytometric assay. , 2011, Journal of visualized experiments : JoVE.

[48]  C. Torp‐Pedersen,et al.  Central obesity and survival in subjects with coronary artery disease: a systematic review of the literature and collaborative analysis with individual subject data. , 2011, Journal of the American College of Cardiology.

[49]  Michael N. Alonso,et al.  B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies , 2011, Nature Medicine.

[50]  M. Czech,et al.  Depot-Specific Differences and Insufficient Subcutaneous Adipose Tissue Angiogenesis in Human Obesity , 2011, Circulation.

[51]  Y. Tseng,et al.  Cellular bioenergetics as a target for obesity therapy , 2010, Nature Reviews Drug Discovery.

[52]  W. D. van Marken Lichtenbelt,et al.  Cold-activated brown adipose tissue in healthy men. , 2009, The New England journal of medicine.

[53]  Y. Even,et al.  Depot‐Specific Differences in Adipogenic Progenitor Abundance and Proliferative Response to High‐Fat Diet , 2009, Stem cells.

[54]  T. Kadowaki,et al.  CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity , 2009, Nature Medicine.

[55]  Christophe Benoist,et al.  Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters , 2009, Nature Medicine.

[56]  B. Spiegelman,et al.  Transcriptional control of brown adipocyte development and physiological function--of mice and men. , 2009, Genes & development.

[57]  Philipp E. Scherer,et al.  Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI , 2008, Molecular and Cellular Biology.

[58]  R. Hammer,et al.  White Fat Progenitor Cells Reside in the Adipose Vasculature , 2008, Science.

[59]  J. Friedman,et al.  Identification of White Adipocyte Progenitor Cells In Vivo , 2008, Cell.

[60]  S. Watkins,et al.  Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism , 2008, Cell.

[61]  Yuji Yamamoto,et al.  Beneficial effects of subcutaneous fat transplantation on metabolism. , 2008, Cell metabolism.

[62]  J. Després,et al.  Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6 and tumor necrosis factor-alpha in men. , 2008, The Journal of clinical endocrinology and metabolism.

[63]  G. Bray,et al.  Relation of central adiposity and body mass index to the development of diabetes in the Diabetes Prevention Program. , 2008, The American journal of clinical nutrition.

[64]  B. Bettler,et al.  Altered peripheral myelination in mice lacking GABAB receptors , 2008, Molecular and Cellular Neuroscience.

[65]  J. Gómez-Reino,et al.  Adipokines as emerging mediators of immune response and inflammation , 2007, Nature Clinical Practice Rheumatology.

[66]  C. Kahn,et al.  Developmental Origin of Fat: Tracking Obesity to Its Source , 2007, Cell.

[67]  Yihai Cao Angiogenesis modulates adipogenesis and obesity. , 2007, The Journal of clinical investigation.

[68]  X. Papademetris,et al.  The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome , 2007, Proceedings of the National Academy of Sciences.

[69]  A. Saltiel,et al.  Obesity induces a phenotypic switch in adipose tissue macrophage polarization. , 2007, The Journal of clinical investigation.

[70]  G. Hotamisligil,et al.  Inflammation and metabolic disorders , 2006, Nature.

[71]  O. MacDougald,et al.  Adipocyte differentiation from the inside out , 2006, Nature Reviews Molecular Cell Biology.

[72]  Herbert Tilg,et al.  Adipocytokines: mediators linking adipose tissue, inflammation and immunity , 2006, Nature Reviews Immunology.

[73]  George Thomas,et al.  Hypothalamic mTOR Signaling Regulates Food Intake , 2006, Science.

[74]  Ting Wang,et al.  The gut microbiota as an environmental factor that regulates fat storage. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[75]  I. Sekiya,et al.  Adipogenic Differentiation of Human Adult Stem Cells From Bone Marrow Stroma (MSCs) , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[76]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[77]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[78]  H. Lodish,et al.  Oligomerization State-dependent Activation of NF-κB Signaling Pathway by Adipocyte Complement-related Protein of 30 kDa (Acrp30)* , 2002, The Journal of Biological Chemistry.

[79]  J. Hardies,et al.  Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. , 2002, The Journal of clinical endocrinology and metabolism.

[80]  E. A. Sims,et al.  Are there persons who are obese, but metabolically healthy? , 2001, Metabolism: clinical and experimental.

[81]  C. Lüscher,et al.  Epilepsy, Hyperalgesia, Impaired Memory, and Loss of Pre- and Postsynaptic GABAB Responses in Mice Lacking GABAB(1) , 2001, Neuron.

[82]  G. Shulman,et al.  Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. , 2001, The Journal of clinical investigation.

[83]  S. O’Rahilly,et al.  Depot-related gene expression in human subcutaneous and omental adipocytes. , 1998, Diabetes.

[84]  B. Spiegelman PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. , 1998, Diabetes.

[85]  R. Seeley,et al.  Identification of targets of leptin action in rat hypothalamus. , 1996, The Journal of clinical investigation.

[86]  B. Spiegelman,et al.  ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. , 1996, Genes & development.

[87]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[88]  B. Lowell,et al.  Development of obesity in transgenic mice after genetic ablation of brown adipose tissue , 1993, Nature.

[89]  J. Heeren,et al.  Adipose tissue browning and metabolic health , 2014, Nature Reviews Endocrinology.

[90]  Jan Nedergaard,et al.  Brown adipose tissue: function and physiological significance. , 2004, Physiological reviews.

[91]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[92]  B. Spiegelman,et al.  Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. , 1993, Science.

[93]  J. Vague,et al.  The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. , 1956, The American journal of clinical nutrition.