Adipocyte-specific expression of a retinoic acid receptor α dominant negative form causes glucose intolerance and hepatic steatosis in mice.
All-trans-retinoic acid (ATRA) has been well described as a positive regulator for early stage of adipocyte differentiation and lipid metabolism and also linked to an in vivo fat-lowering effect in mice. However, not all studies support this association. Our objective was to characterize the action of ATRA in mature adipocytes of mice by ablating RAR signaling through overexpression of a well-characterized dominant negative RARα mutant (RARdn) form specifically in adipocytes. Altered RAR signaling in adipocytes resulted in a significant decrease in ATRA levels in visceral and brown adipose tissues as well as liver tissue. This was linked to significant impairments in glucose clearance and elevated hepatic lipid accumulation for chow diet fed mice, indicating the development of metabolic disease, including hepatic steatosis. In addition, we found that adipose RARdn expression in mice fed a chow diet decreased thermogenesis. We conclude that altered RAR signaling and ATRA levels in adipocytes impacts glucose and lipid metabolism in mice.
['Lee|Seung-Ah|SA|', 'Jiang|Hongfeng|H|', 'Feranil|Jun B|JB|', 'Brun|Pierre-Jacques|PJ|', 'Blaner|William S|WS|']
D017667:Adipocytes D000818:Animals D005234:Fatty Liver D018149:Glucose Intolerance D051379:Mice D008822:Mice, Transgenic D000072482:Retinoic Acid Receptor alpha D015398:Signal Transduction
Glucose intolerance Hepatic steatosis All-trans-retinoic acid (ATRA) Heat production Retinoic acid receptor (RAR) signaling