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

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Abstract
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 .