The gut microbiota suppresses insulin-mediatedfat accumulation via the short-chain fatty acidreceptor GPR43

摘要

The gut microbiota affects nutrient acquisition and energy regulation of the host, and caninfluence the development of obesity, insulin resistance, and diabetes. During feeding, gutmicrobes produce short-chain fatty acids, which are important energy sources for the host.Here we show that the short-chain fatty acid receptor GPR43 links the metabolic activity ofthe gut microbiota with host body energy homoeostasis. We demonstrate that GPR43-deficient mice are obese on a normal diet, whereas mice overexpressing GPR43 specifically inadipose tissue remain lean even when fed a high-fat diet. Raised under germ-free conditionsor after treatment with antibiotics, both types of mice have a normal phenotype. We furthershow that short-chain fatty acid-mediated activation of GPR43 suppresses insulin signalling inadipocytes, which inhibits fat accumulation in adipose tissue and promotes the metabolism ofunincorporated lipids and glucose in other tissues. These findings establish GPR43 as asensor for excessive dietary energy, thereby controlling body energy utilization while maintainingmetabolic homoeostasis.