Retinoic Acid Mediates Visceral-specific Adipogenic Defects of Human Adipose-derived Stem Cells

Retinoic Acid Mediates Visceral-specific Adipogenic Defects of Human Adipose-derived Stem Cells
Title:
Retinoic Acid Mediates Visceral-specific Adipogenic Defects of Human Adipose-derived Stem Cells
Other Titles:
Diabetes
Keywords:
Publication Date:
02 March 2016
Citation:
Diabetes 2016 May; 65(5): 1164-1178
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.
License type:
PublisherCopyrights
Funding Info:
Description:
“This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at [http://dx.doi.org/10.2337/db15-1315: http://care.diabetesjournals.org, http://diabetes.diabetesjournals.org, http://clinical.diabetesjournals.org, or http://spectrum.diabetesjournals.org].”
ISSN:
0012-1797
1939-327X
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