title: Retinoic Acid Mediates Visceral-Specific Adipogenic Defects of Human Adipose-Derived Stem Cells.
abstract: Increased visceral fat, rather than subcutaneous fat, during the onset of obesity is associated with a higher risk of developing metabolic diseases. The inherent adipogenic properties of human adipose-derived stem cells (ASCs) from visceral depots are compromised compared with those of ASCs from subcutaneous depots, but little is known about the underlying mechanisms. Using ontological analysis of global gene expression studies, we demonstrate that many genes involved in retinoic acid (RA) synthesis or regulated by RA are differentially expressed in human tissues and ASCs from subcutaneous and visceral fat. The endogenous level of RA is higher in visceral ASCs; this is associated with upregulation of the RA synthesis gene through the visceral-specific developmental factor WT1. Excessive RA-mediated activity impedes the adipogenic capability of ASCs at early but not late stages of adipogenesis, which can be reversed by antagonism of RA receptors or knockdown of WT1. Our results reveal the developmental origin of adipocytic properties and the pathophysiological contributions of visceral fat depots.
authors.affiliation: Fat Metabolism and Stem Cell Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Fat Metabolism and Stem Cell Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Sriram
authors.affiliation: Fat Metabolism and Stem Cell Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore.
authors.forename: Xin Hui Derryn
authors.initials: XH
authors.lastname: Chan
authors.affiliation: Fat Metabolism and Stem Cell Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore.
authors.forename: Wee Kiat
authors.initials: WK
authors.lastname: Ong
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Chia Rou
authors.initials: CR
authors.lastname: Yeo
authors.affiliation: Bioinformatics Institute, A*STAR, Singapore.
authors.forename: Betty
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Bio-optical Imaging Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore.
authors.forename: Kien Voon
authors.initials: KV
authors.lastname: Kong
authors.affiliation: Molecular Engineering Lab, A*STAR, Singapore.
authors.forename: Shawn
authors.initials: S
authors.lastname: Hoon
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Yuen
authors.affiliation: Bio-optical Imaging Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore.
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Perumal
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Madhur
authors.initials: M
authors.lastname: Agrawal
authors.affiliation: Bioinformatics Institute, A*STAR, Singapore.
authors.forename: Candida
authors.initials: C
authors.lastname: Vaz
authors.affiliation: Department of Surgery, National University Hospital, Singapore.
authors.forename: Jimmy
authors.initials: J
authors.lastname: So
authors.affiliation: Department of Surgery, National University Hospital, Singapore.
authors.forename: Asim
authors.initials: A
authors.lastname: Shabbir
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.affiliation: Bio-optical Imaging Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore.
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
authors.affiliation: Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore.
authors.forename: Weiping
authors.initials: W
authors.lastname: Han
authors.affiliation: Bioinformatics Institute, A*STAR, Singapore Institute of Medical Biology, A*STAR, Singapore.
authors.forename: Vivek
authors.initials: V
authors.lastname: Tanavde
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Sue-Anne
authors.initials: SA
authors.lastname: Toh
authors.affiliation: Fat Metabolism and Stem Cell Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, Singapore Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore shigeki_sugii@sbic.a-star.edu.sg.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sugii
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050110:Bariatric Surgery; D001565:Benzoates / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D063990:Gene Ontology; D006801:Humans; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology; D009767:Obesity, Morbid / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D034622:RNA Interference; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D025721:WT1 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C542472:4-(2-(5,6-dihydro-5,5-dimethyl-8-(2-phenylethynyl)naphthalen-2-yl)ethen-1-yl)benzoic acid; D001565:Benzoates; D009281:Naphthalenes; D018168:Receptors, Retinoic Acid; D013267:Stilbenes; D025721:WT1 Proteins; C583751:WT1 protein, human; D014212:Tretinoin