Retinoic acid mediates visceral-specific adipogenic defects of human adipose-derived stem cells
Journal
Diabetes
Journal Volume
65
Journal Issue
5
Pages
1164-1178
Date Issued
2016
Author(s)
Takeda, K.
Sriram, S.
Chan, X.H.D.
Ong, W.K.
Yeo, C.R.
Tan, B.
Lee, S.-A.
Hoon, S.
Jiang, H.
Yuen, J.J.
Perumal, J.
Agrawal, M.
Vaz, C.
So, J.
Shabbir, A.
Blaner, W.S.
Olivo, M.
Han, W.
Tanavde, V.
Toh, S.-A.
Sugii, S.
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.
SDGs
Type
journal article