Endocrine Abstracts

JOINT449

The existing anti-obese therapies mainly target to cut down the energy intake, which is often associated with neuro-endocrine side effects². On the other hand, therapies to safely augment energy expenditure are lacking. Compelling evidence have shown that activation of adipose browning is sufficient to confer protection against a panel of metabolic disorders including obesity, diabetes and cardiovascular diseases. Here we found that rhein, the major component in the traditional Chinese medicine Rhubarb, robustly increased energy expenditure and adipose tissue browning in obese mice. Further analysis showed that Rhein-induced energy expenditure was mainly orchestrated through SIRT1 in adipocytes, as adipocyte-selective deletion of Sirt1 gene almost completely mitigated Rhein-induced effect on enhancing adipose energy expenditure. By pull-down assay, ARGLU1, a transcriptional co-regulator of glucocorticoid receptor, was identified as a protein that directly binds with rhein in adipocytes. Rhein-induced adipocyte browning was abolished In vitro upon overexpression of ARGLU1. Furthermore, in mice receiving glucocorticoid, supplementation of rhein rescued glucocorticoid-induced obesity, insulin resistance, and most importantly impairment of adipose browning. In conclusion, here we unravel the new mechanism underlying the anti-obese effect of rhein, which is achieved through modulating the activity of glucocorticoid receptor.