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PMID: 23652017 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature communications ·Vol. 4 ·2013-00-00 ·Pages 1829

Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T, Takahashi T, Miyauchi S, Shioi G, Inoue H, Tsujimoto G

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.

MeSH Terms
Adipose Tissue, White/metabolism Animals Energy Metabolism Fatty Acids, Volatile/metabolism GTP-Binding Protein alpha Subunits, Gi-Go/metabolism GTP-Binding Protein beta Subunits/metabolism GTP-Binding Protein gamma Subunits/metabolism Gastrointestinal Tract/microbiology Insulin/metabolism Lipid Metabolism Liver/metabolism,pathology Male Mice Mice, Knockout Microbiota Models, Biological Muscles/metabolism,pathology Obesity/metabolism,pathology Organ Specificity PTEN Phosphohydrolase/metabolism Protein Kinase C/metabolism Receptors, G-Protein-Coupled/deficiency,metabolism Signal Transduction Thinness/metabolism,pathology Type C Phospholipases/metabolism
Chemicals
Fatty Acids, Volatile Ffar2 protein, mouse GTP-Binding Protein beta Subunits GTP-Binding Protein gamma Subunits Insulin Receptors, G-Protein-Coupled Protein Kinase C PTEN Phosphohydrolase Pten protein, mouse Type C Phospholipases GTP-Binding Protein alpha Subunits, Gi-Go
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Kimura Ikuo
Department of Pharmacogenomics, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo-ku, Kyoto 606-8501, Japan. ikimura@pharm.kyoto-u.ac.jp
Ozawa Kentaro
Inoue Daisuke
Imamura Takeshi
Kimura Kumi
Maeda Takeshi
Terasawa Kazuya
Kashihara Daiji
Hirano Kanako
Tani Taeko
Takahashi Tomoyuki
Miyauchi Satoshi
Shioi Go
Inoue Hiroshi
Tsujimoto Gozoh
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms2852
Email
ikimura@pharm.kyoto-u.ac.jp
Published
2013-00-00
Pages
1829
Language
English
Region
England
NLM ID
101528555
PMCID
PMC3674247
Subset
IM
External Links
PubMed source DOI: 10.1038/ncomms2852 PMC Full Text View journal details
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