Editors' ChoiceMETABOLIC REGULATION

Dietary Fatty Acids Stimulate Leptin Production

Science's STKE  03 Feb 2004:
Vol. 2004, Issue 218, pp. tw43-TW43
DOI: 10.1126/stke.2182004TW43

The mammalian hormone leptin has been linked to suppressing food intake and regulating energy balance. Some regulators of leptin expression in adipocytes act through G protein-coupled receptors (GPCRs). Xiong et al. have determined that an orphan GPCR called GPR41 is expressed in human and mouse adipose tissue. A screen for activating ligands identified short-chain fatty acids, a major energy source in the mammalian diet. Furthermore, overexpression of GPR41 and exposure to short-chain fatty acids increased leptin production in cultured mouse adipocytes, whereas knockdown of the receptor by RNA interference abolished this stimulatory effect. Treatment of adipocytes with pertussis toxin, an inhibitor of the Gi subtype of receptors, also blocked the effect of fatty acid on leptin expression. Oral administration of a fatty acid increased circulating leptin. The study establishes a role for fatty acid molecules in the leptin pathway.

Y. Xiong, N. Miyamoto, K. Shibata, M. A. Valasek, T. Motoike, R. M. Kedzierski, M. Yanagisawa, Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GRP41. Proc. Natl. Acad. Sci. U.S.A. 101, 1045-1050 (2004). [Abstract] [Full Text]