The Gut Microbiota Suppresses Insulin-mediated Fat Accumulation Via the Short-chain Fatty Acid Receptor GPR43

Overview

Journal Nat Commun

Specialty Biology

Date 2013 May 9

PMID 23652017

Citations 629

Authors

Ikuo Kimura

Kentaro Ozawa

Daisuke Inoue

Takeshi Imamura

Kumi Kimura

Takeshi Maeda

Kazuya Terasawa

Daiji Kashihara

Kanako Hirano

Taeko Tani

Tomoyuki Takahashi

Satoshi Miyauchi

Go Shioi

Hiroshi Inoue

Gozoh Tsujimoto

Affiliations

Soon will be listed here.

Abstract

The gut microbiota affects nutrient acquisition and energy regulation of the host, and can influence the development of obesity, insulin resistance, and diabetes. During feeding, gut microbes 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 of the gut microbiota with host body energy homoeostasis. We demonstrate that GPR43-deficient mice are obese on a normal diet, whereas mice overexpressing GPR43 specifically in adipose tissue remain lean even when fed a high-fat diet. Raised under germ-free conditions or after treatment with antibiotics, both types of mice have a normal phenotype. We further show that short-chain fatty acid-mediated activation of GPR43 suppresses insulin signalling in adipocytes, which inhibits fat accumulation in adipose tissue and promotes the metabolism of unincorporated lipids and glucose in other tissues. These findings establish GPR43 as a sensor for excessive dietary energy, thereby controlling body energy utilization while maintaining metabolic homoeostasis.

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