{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:46:02Z","timestamp":1792197962706,"version":"4.4.0"},"reference-count":121,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-17-JDF-055"],"award-info":[{"award-number":["1-17-JDF-055"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Adipose tissue not only stores energy, but also controls metabolism through secretion of hormones, cytokines, proteins, and microRNAs that affect the function of cells and tissues throughout the body. Adipose tissue is organized into discrete depots throughout the body, and these depots are differentially associated with insulin resistance and increased risk of metabolic disease. In addition to energy-dissipating brown and beige adipocytes, recent lineage tracing studies have demonstrated that individual adipose depots are composed of white adipocytes that are derived from distinct precursor populations, giving rise to distinct subpopulations of energy-storing white adipocytes. In this review, we discuss this developmental and functional heterogeneity of white adipocytes both between and within adipose depots. In particular, we will highlight findings from our recent manuscript in which we find and characterize three major subtypes of white adipocytes. We will discuss these data relating to the differences between subcutaneous and visceral white adipose tissue and in relationship to previous work deciphering adipocyte heterogeneity within adipose tissue depots. Finally, we will discuss the possible implications of adipocyte heterogeneity may have for the understanding of lipodystrophies.<\/jats:p>","DOI":"10.3390\/biology8020023","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T03:46:37Z","timestamp":1555040797000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Deciphering White Adipose Tissue Heterogeneity"],"prefix":"10.3390","volume":"8","author":[{"given":"Quyen","family":"Luong","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"The Diabetes Institute, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"The Diabetes Institute, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"The Diabetes Institute, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/sj.ijo.0802326","article-title":"Integrative physiology of human adipose tissue","volume":"27","author":"Frayn","year":"2003","journal-title":"Int. J. Obes."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2174\/1389450043490523","article-title":"Adipose tissue as a regulator of energy balance","volume":"5","author":"Klaus","year":"2004","journal-title":"Curr. Drug Targets"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrd.2016.75","article-title":"Targeting adipose tissue in the treatment of obesity-associated diabetes","volume":"15","author":"Kusminski","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nature05483","article-title":"Adipocytes as regulators of energy balance and glucose homeostasis","volume":"444","author":"Rosen","year":"2006","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stephens, J.M. (2012). The Fat Controller: Adipocyte Development. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001436"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature21365","article-title":"Adipose-derived circulating miRNAs regulate gene expression in other tissues","volume":"542","author":"Thomou","year":"2017","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1210\/er.2006-0033","article-title":"Adipose tissue-derived factors: Impact on health and disease","volume":"27","author":"Trujillo","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cell.2014.09.035","article-title":"Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects","volume":"159","author":"Yore","year":"2014","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/MED.0b013e328337a81f","article-title":"Brown fat as a therapy for obesity and diabetes","volume":"17","author":"Cypess","year":"2010","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e99291","DOI":"10.15252\/embj.201899291","article-title":"Developmental and functional heterogeneity of white adipocytes within a single fat depot","volume":"38","author":"Lee","year":"2018","journal-title":"EMBO J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1038\/ncomms5099","article-title":"Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed","volume":"5","author":"Guertin","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.stemcr.2015.02.008","article-title":"Highly Selective In Vivo Labeling of Subcutaneous White Adipocyte Precursors with Prx1-Cre","volume":"4","author":"Hsiao","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nature12783","article-title":"Distinct fibroblast lineages determine dermal architecture in skin development and repair","volume":"504","author":"Driskell","year":"2013","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/exd.12941","article-title":"Dermal adipocytes and hair cycling: Is spatial heterogeneity a characteristic feature of the dermal adipose tissue depot?","volume":"25","author":"Kruglikov","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1194\/jlr.R062893","article-title":"Dermal white adipose tissue: A new component of the thermogenic response","volume":"56","author":"Alexander","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/exd.12450","article-title":"Defining dermal adipose tissue","volume":"23","author":"Driskell","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wojciechowicz, K., Gledhill, K., Ambler, C.A., Manning, C.B., and Jahoda, C.A.B. (2013). Development of the Mouse Dermal Adipose Layer Occurs Independently of Subcutaneous Adipose Tissue and Is Marked by Restricted Early Expression of FABP4. PLoS ONE, 8.","DOI":"10.1371\/annotation\/cf897d66-612e-42a7-a247-9979e4a61a8d"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chen, J., Shi, Y., Regan, J., Karuppaiah, K., Ornitz, D.M., and Long, F. (2014). Osx-Cre targets multiple cell types besides osteoblast lineage in postnatal mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085161"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s40610-018-0087-9","article-title":"Molecular differences between subtypes of bone marrow adipocytes","volume":"4","author":"Craft","year":"2018","journal-title":"Curr. Mol. Biol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"694","DOI":"10.3389\/fendo.2018.00694","article-title":"Bone Marrow Fat and Hematopoiesis","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1359\/jbmr.1997.12.11.1772","article-title":"Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia","volume":"12","author":"Kajkenova","year":"1997","journal-title":"J. Bone Miner. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1002\/jbmr.82","article-title":"Caloric restriction leads to high marrow adiposity and low bone mass in growing mice","volume":"25","author":"Devlin","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/jmri.24908","article-title":"MR-detected changes in liver fat, abdominal fat, and vertebral bone marrow fat after a four-week calorie restriction in obese women","volume":"42","author":"Cordes","year":"2015","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1210\/jc.2008-2532","article-title":"Increased bone marrow fat in anorexia nervosa","volume":"94","author":"Bredella","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.cmet.2014.06.003","article-title":"Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction","volume":"20","author":"Cawthorn","year":"2014","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1096\/fj.201800948RR","article-title":"Progenitor recruitment and adipogenic lipolysis contribute to the anabolic actions of parathyroid hormone on the skeleton","volume":"33","author":"Maridas","year":"2019","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41580-018-0093-z","article-title":"Adipogenesis and metabolic health","volume":"20","author":"Ghaben","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1161\/CIRCULATIONAHA.106.675355","article-title":"Abdominal visceral and subcutaneous adipose tissue compartments: Association with metabolic risk factors in the Framingham Heart Study","volume":"116","author":"Fox","year":"2007","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1210\/jcem-54-2-254","article-title":"Relation of body fat distribution to metabolic complications of obesity","volume":"54","author":"Kissebah","year":"1982","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5098","DOI":"10.1210\/jc.2002-020696","article-title":"Metabolic Effects of Visceral Fat Accumulation in Type 2 Diabetes","volume":"87","author":"Gastaldelli","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18495","DOI":"10.1038\/srep18495","article-title":"Associations of Different Adipose Tissue Depots with Insulin Resistance: A Systematic Review and Meta-analysis of Observational Studies","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.2337\/db14-0704","article-title":"A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis","volume":"64","author":"Stanford","year":"2015","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.cmet.2008.04.004","article-title":"Beneficial effects of subcutaneous fat transplantation on metabolism","volume":"7","author":"Tran","year":"2008","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.cmet.2013.03.008","article-title":"Mechanisms and metabolic implications of regional differences among fat depots","volume":"17","author":"Tchkonia","year":"2013","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6676","DOI":"10.1073\/pnas.0601752103","article-title":"Evidence for a role of developmental genes in the origin of obesity and body fat distribution","volume":"103","author":"Gesta","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11409","DOI":"10.1073\/pnas.1310331110","article-title":"Shox2 is a molecular determinant of depot-specific adipocyte function","volume":"110","author":"Lee","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.2337\/db11-1753","article-title":"Intrinsic differences in adipocyte precursor cells from different white fat depots","volume":"61","author":"Macotela","year":"2012","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"R1286","DOI":"10.1152\/ajpregu.00653.2001","article-title":"Fat depot origin affects adipogenesis in primary cultured and cloned human preadipocytes","volume":"282","author":"Tchkonia","year":"2002","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.2337\/db06-0540","article-title":"Fat depot-specific characteristics are retained in strains derived from single human preadipocytes","volume":"55","author":"Tchkonia","year":"2006","journal-title":"Diabetes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"98","DOI":"10.2337\/diab.47.1.98","article-title":"Depot-specific differences in adipose tissue gene expression in lean and obese subjects","volume":"47","author":"Lefebvre","year":"1998","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.molmet.2016.09.001","article-title":"Depot-specific differences in angiogenic capacity of adipose tissue in differential susceptibility to diet-induced obesity","volume":"5","author":"Song","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/j.1550-8528.1993.tb00596.x","article-title":"Two Preadipocyte Subtypes Cloned from Human Omental Fat","volume":"1","author":"Kirkland","year":"1993","journal-title":"Obes. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"E267","DOI":"10.1152\/ajpendo.00265.2004","article-title":"Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots","volume":"288","author":"Tchkonia","year":"2005","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/oby.2004.153","article-title":"A Survey of Genes Differentially Expressed in Subcutaneous and Visceral Adipose Tissue in Men","volume":"12","author":"Vohl","year":"2004","journal-title":"Obes. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1038\/oby.2010.56","article-title":"Sex- and depot-dependent differences in adipogenesis in normal-weight humans","volume":"18","author":"Tchoukalova","year":"2010","journal-title":"Obesity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.diabet.2008.04.001","article-title":"Impact of visceral adipose tissue on liver metabolism","volume":"34","author":"Lafontan","year":"2008","journal-title":"Diabetes Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1172\/JCI114880","article-title":"Beta-adrenoceptor expression in human fat cells from different regions","volume":"86","author":"Arner","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/0026-0495(91)90078-B","article-title":"Regional differences in triglyceride breakdown in human adipose tissue: Effects of catecholamines, insulin, and prostaglandin E2","volume":"40","author":"Richelsen","year":"1991","journal-title":"Metabolism"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/0026-0495(79)90131-8","article-title":"Regional differences in the control of lipolysis in human adipose tissue","volume":"28","author":"Arner","year":"1979","journal-title":"Metabolism"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fcvm.2017.00027","article-title":"Humans and Mice Display Opposing Patterns of \u201cBrowning\u201d Gene Expression in Visceral and Subcutaneous White Adipose Tissue Depots","volume":"4","author":"Zuriaga","year":"2017","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.2337\/db15-0227","article-title":"Exercise Effects on White Adipose Tissue: Beiging and Metabolic Adaptations","volume":"64","author":"Stanford","year":"2015","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"557","DOI":"10.3945\/ajcn.116.132563","article-title":"Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss","volume":"104","author":"Nakhuda","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/ijo.2009.286","article-title":"Gluteofemoral body fat as a determinant of metabolic health","volume":"34","author":"Manolopoulos","year":"2010","journal-title":"Int. J. Obes."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1038\/oby.2007.231","article-title":"Deep subcutaneous adipose tissue: A distinct abdominal adipose depot","volume":"15","author":"Walker","year":"2007","journal-title":"Obesity"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/ijo.2012.72","article-title":"Deep subcutaneous adipose tissue is more saturated than superficial subcutaneous adipose tissue","volume":"37","author":"Lundbom","year":"2013","journal-title":"Int. J. Obes."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1002\/oby.20417","article-title":"Molecular and morphologic characterization of superficial- and deep-subcutaneous adipose tissue subdivisions in human obesity","volume":"21","author":"Cancello","year":"2013","journal-title":"Obesity"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"E941","DOI":"10.1152\/ajpendo.2000.278.5.E941","article-title":"Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance","volume":"278","author":"Kelley","year":"2000","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E298","DOI":"10.1152\/ajpendo.00202.2006","article-title":"Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns","volume":"292","author":"Tchkonia","year":"2007","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/s41467-018-03196-x","article-title":"De novo adipocyte differentiation from Pdgfr\u03b2+ preadipocytes protects against pathologic visceral adipose expansion in obesity","volume":"9","author":"Shao","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.celrep.2014.06.060","article-title":"Pref-1 marks very early mesenchymal precursors required for adipose tissue development and expansion","volume":"8","author":"Hudak","year":"2014","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.cell.2008.09.036","article-title":"Identification of White Adipocyte Progenitor Cells In Vivo","volume":"135","author":"Rodeheffer","year":"2008","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/ncb2696","article-title":"Characterization of the adipocyte cellular lineage in vivo","volume":"15","author":"Berry","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1111\/j.1582-4934.2010.01212.x","article-title":"Mesothelial cell differentiation into osteoblast- and adipocyte-like cells","volume":"15","author":"Lansley","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/ncb2922","article-title":"Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source","volume":"16","author":"Chau","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1242\/dev.080549","article-title":"The developmental origins of adipose tissue","volume":"140","author":"Berry","year":"2013","journal-title":"Development"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1126\/science.1156232","article-title":"White Fat Progenitors Reside in the Adipose Vasculature","volume":"322","author":"Tang","year":"2008","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.celrep.2014.09.049","article-title":"Independent stem cell lineages regulate adipose organogenesis and adipose homeostasis","volume":"9","author":"Jiang","year":"2014","journal-title":"Cell Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.cmet.2014.03.025","article-title":"A smooth muscle-like origin for beige adipocytes","volume":"19","author":"Long","year":"2014","journal-title":"Cell Metab."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Klein, D., Weisshardt, P., Kleff, V., Jastrow, H., Jakob, H.G., and Erg\u00fcn, S. (2011). Vascular wall-resident CD44+ multipotent stem cells give rise to pericytes and smooth muscle cells and contribute to new vessel maturation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020540"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/nature08816","article-title":"Transcriptional control of preadipocyte determination by Zfp423","volume":"464","author":"Gupta","year":"2010","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.cmet.2012.01.010","article-title":"Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells","volume":"15","author":"Gupta","year":"2012","journal-title":"Cell Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.cmet.2012.01.008","article-title":"The vascular endothelium of the adipose tissue give rise to both white and brown fat cells","volume":"15","author":"Tran","year":"2012","journal-title":"Cell Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"14781","DOI":"10.1073\/pnas.1003512107","article-title":"De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific","volume":"107","author":"Majka","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"215","DOI":"10.4161\/adip.21496","article-title":"Adipose lineage specification of bone marrow-derived myeloid cells","volume":"1","author":"Majka","year":"2012","journal-title":"Adipocyte"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1634\/stemcells.2007-0567","article-title":"Characterization of transplanted green fluorescent protein+ bone marrow cells into adipose tissue","volume":"26","author":"Tomiyama","year":"2008","journal-title":"Stem Cells"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fendo.2018.00276","article-title":"Ovarian Hormones Regulate the Production of Adipocytes From Bone Marrow-Derived Cells","volume":"9","author":"Gavin","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1096\/fj.15-278994","article-title":"De novo generation of adipocytes from circulating progenitor cells in mouse and human adipose tissue","volume":"30","author":"Gavin","year":"2016","journal-title":"FASEB J."},{"key":"ref_78","first-page":"125","article-title":"Mesenchymal derivatives of the neural crest: Analysis of chimaeric quail and chick embryos","volume":"34","year":"1975","journal-title":"J. Embryol. Exp. Morphol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1242\/dev.002642","article-title":"The generation of adipocytes by the neural crest","volume":"134","author":"Billon","year":"2007","journal-title":"Development"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature03837","article-title":"Neural crest origins of the neck and shoulder","volume":"436","author":"Matsuoka","year":"2005","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1002\/stem.1082","article-title":"Functionally Convergent White Adipogenic Progenitors of Different Lineages Participate in a Diffused System Supporting Tissue Regeneration","volume":"30","author":"Lemos","year":"2012","journal-title":"Stem Cells"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Sebo, Z.L., Jeffery, E., Holtrup, B., and Rodeheffer, M.S. (2018). A mesodermal fate map for adipose tissue. Development.","DOI":"10.1242\/dev.166801"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.stemcr.2014.10.009","article-title":"Characterization of Cre recombinase activity for in vivo targeting of adipocyte precursor cells","volume":"3","author":"Krueger","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1172\/JCI106623","article-title":"The effect of insulin upon glucose metabolism by adipose cells of different size. Influence of cell lipid and protein content, age, and nutritional state","volume":"50","author":"Salans","year":"1971","journal-title":"J. Clin. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1210\/en.2014-1699","article-title":"Cell-autonomous heterogeneity of nutrient uptake in white adipose tissue of rhesus macaques","volume":"156","author":"Varlamov","year":"2015","journal-title":"Endocrinology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1113\/jphysiol.1974.sp010449","article-title":"Lipogenesis and insulin sensitivity of single fat cells","volume":"236","author":"Gliemann","year":"1974","journal-title":"J. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0898-6568(95)02035-7","article-title":"Adrenoceptor heterogeneity in human white adipocytes differentiated in culture as assessed by cytosolic free calcium measurements","volume":"8","author":"Seydoux","year":"1996","journal-title":"Cell. Signal."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"E335","DOI":"10.1152\/ajpendo.00075.2014","article-title":"Heritability of fat accumulation in white adipocytes","volume":"307","author":"Katz","year":"2014","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1016\/j.celrep.2018.08.006","article-title":"Flow Cytometry of Mouse and Human Adipocytes for the Analysis of Browning and Cellular Heterogeneity","volume":"24","author":"Hagberg","year":"2018","journal-title":"Cell Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8054","DOI":"10.1038\/ncomms9054","article-title":"Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism","volume":"6","author":"Lee","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.2337\/db17-0218","article-title":"Tbx15 Defines a Glycolytic Subpopulation and White Adipocyte Heterogeneity","volume":"66","author":"Lee","year":"2017","journal-title":"Diabetes"},{"key":"ref_92","first-page":"e18","article-title":"Epicardial fat: Definition, measurements and systematic review of main outcomes","volume":"101","author":"Bertaso","year":"2013","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/oby.2008.575","article-title":"Epicardial and pericardial fat: Close, but very different","volume":"17","author":"Iacobellis","year":"2009","journal-title":"Obesity"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1467-789X.2006.00293.x","article-title":"Epicardial fat: Properties, function and relationship to obesity","volume":"8","author":"Rabkin","year":"2007","journal-title":"Obes. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/ncpcardio0319","article-title":"Epicardial adipose tissue: Anatomic, biomolecular and clinical relationships with the heart","volume":"2","author":"Iacobellis","year":"2005","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1161\/01.CIR.0000099542.57313.C5","article-title":"Human epicardial adipose tissue is a source of inflammatory mediators","volume":"108","author":"Mazurek","year":"2003","journal-title":"Circulation"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jacc.2011.01.048","article-title":"Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue","volume":"58","author":"Hirata","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1161\/ATVBAHA.112.300829","article-title":"Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis","volume":"33","author":"Shimabukuro","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.cmet.2018.05.025","article-title":"Deconstructing Adipogenesis Induced by \u03b23-Adrenergic Receptor Activation with Single-Cell Expression Profiling","volume":"28","author":"Burl","year":"2018","journal-title":"Cell Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/s41586-018-0226-8","article-title":"A stromal cell population that inhibits adipogenesis in mammalian fat depots","volume":"559","author":"Schwalie","year":"2018","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/scrt468","article-title":"Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations","volume":"5","author":"Rennert","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"11945","DOI":"10.1038\/ncomms11945","article-title":"Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies","volume":"7","author":"Rennert","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Zhang, R., Gao, Y., Zhao, X., Gao, M., Wu, Y., Han, Y., Qiao, Y., Luo, Z., Yang, L., and Chen, J. (2018). FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2001493"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1172\/JCI111075","article-title":"Influence of anatomic site and age on the replication and differentiation of rat adipocyte precursors in culture","volume":"72","author":"Djian","year":"1983","journal-title":"J. Clin. Investig."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"C206","DOI":"10.1152\/ajpcell.1990.258.2.C206","article-title":"Age, anatomic site, and the replication and differentiation of adipocyte precursors","volume":"258","author":"Kirkland","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1172\/JCI114075","article-title":"Varying capacities for replication of rat adipocyte precursor clones and adipose tissue growth","volume":"83","author":"Wang","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1194\/jlr.M079152","article-title":"Agpat4\/Lpaat\u03b4 deficiency highlights the molecular heterogeneity of epididymal and perirenal white adipose depots","volume":"58","author":"Mardian","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1194\/jlr.M500553-JLR200","article-title":"Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity","volume":"47","author":"Vergnes","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_109","first-page":"358","article-title":"Peculiar distribution of adipose tissue in patients with congenital generalized lipodystrophy","volume":"75","author":"Garg","year":"1992","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.2337\/diacare.26.5.1350","article-title":"Risk factors for diabetes in familial partial lipodystrophy, Dunnigan variety","volume":"26","author":"Haque","year":"2003","journal-title":"Diabetes Care"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.1210\/jc.2003-031658","article-title":"Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities","volume":"89","author":"Vantyghem","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_112","first-page":"408","article-title":"A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy","volume":"87","author":"Agarwal","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1056\/NEJMoa1007487","article-title":"Perilipin deficiency and autosomal dominant partial lipodystrophy","volume":"364","author":"Gandotra","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1126\/science.1096706","article-title":"A family with severe insulin resistance and diabetes due to a mutation in AKT2","volume":"304","author":"George","year":"2004","journal-title":"Science"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/emmm.200900037","article-title":"Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC","volume":"1","author":"Puri","year":"2009","journal-title":"EMBO Mol. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"317","DOI":"10.14310\/horm.2002.1585","article-title":"Familial partial lipodystrophy type 3: A new mutation on the PPARG gene","volume":"14","author":"Lau","year":"2015","journal-title":"Hormones"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.amjms.2016.05.007","article-title":"Barraquer-Simons Syndrome","volume":"352","author":"Small","year":"2016","journal-title":"Am. J. Med. Sci."},{"key":"ref_118","unstructured":"Quinn, K., and Purcell, S.M. (2018). Lipodystrophies. StatPearls, StatPearls Publishing."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/jhg.2013.107","article-title":"Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies","volume":"59","author":"Nolis","year":"2014","journal-title":"J. Hum. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1155\/2005\/303141","article-title":"HIV-associated lipodystrophy syndrome: A review of clinical aspects","volume":"16","author":"Baril","year":"2005","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1752-1947-5-70","article-title":"Development of Buffalo Hump in the course of antiretroviral therapy including raltegravir and unboosted atazanavir: A case report and review of the literature","volume":"5","author":"Ceccarelli","year":"2011","journal-title":"J. Med. Case Rep."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/8\/2\/23\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:44:32Z","timestamp":1760186672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/8\/2\/23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,11]]},"references-count":121,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["biology8020023"],"URL":"https:\/\/doi.org\/10.3390\/biology8020023","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,11]]}}}