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Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):1045-50. Epub 2004 Jan 13.

Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41.

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Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.


Leptin is an adipose-derived hormone that regulates a wide variety of physiological processes, including feeding behavior, metabolic rate, sympathetic nerve activity, reproduction, and immune response. Circulating leptin levels are tightly regulated according to energy homeostasis in vivo. Although mechanisms for the regulation of leptin production in adipocytes are not well understood, G protein-coupled receptors may play an important role in this adipocyte function. Here we report that C2-C6 short-chain fatty acids, ligands of an orphan G protein-coupled receptor GPR41, stimulate leptin expression in both a mouse adipocyte cell line and mouse adipose tissue in primary culture. Acute oral administration of propionate increases circulating leptin levels in mice. The concentrations of short-chain fatty acids required to stimulate leptin production are within physiological ranges, suggesting the relevance of this pathway in vivo.

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