Increased visceral fat, rather than subcutaneous fat, during obesity onset is associated with higher risk of developing metabolic diseases. Human adipose-derived stem cells (ASCs) from visceral depots are compromised in their inherent adipogenic properties compared to ASCs from subcutaneous depots, but little is known about the underlying mechanisms. By ontology 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, associated with upregulation of RA synthetic gene through visceral-specific developmental factor WT1. The excessive RA-mediated activity impedes adipogenic capability of ASCs at early but not late stages of adipogenesis, which can be reversed by antagonism of RA receptors (RARs) or knockdown of WT1. Together our results reveal the developmental origin affecting adipocytic properties and pathophysiological contributions of visceral fat depots.
- Received September 18, 2015.
- Accepted February 19, 2016.
- © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.