Research Abstract


The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43

2013年5月7日 Nature Communications 4 : 1829 doi: 10.1038/ncomms2852


木村 郁夫1, 小澤 健太郎2, 井上 大輔1, 今村 武史3, 木村 久美4, 前田 岳志1, 寺澤 和哉1, 柏原 大二1, 平野 加奈子1, 谷 妙子1, 高橋 知行1, 宮内 諭1, 塩井 剛5, 井上 啓4 & 辻本 豪三1,6

  1. 京都大学大学院 薬学研究科 薬理ゲノミクス
  2. 奈良県立医科大学 薬理学部
  3. 滋賀医科大学 薬理学部
  4. 金沢大学 脳・肝インターフェイスメディシン研究センター 生体統御学部門(代謝生理学)
  5. 理化学研究所 発生・再生科学総合研究センター 動物資源開発室
  6. 京都大学大学院 薬学研究科 ゲノム創薬科学
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.