title: The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43.
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.
authors: Department of Pharmacogenomics, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo-ku, Kyoto 606-8501, Japan. ikimura@pharm.kyoto-u.ac.jp
authors: Ikuo
authors: I
authors: Kimura
authors: Kentaro
authors: K
authors: Ozawa
authors: Daisuke
authors: D
authors: Inoue
authors: Takeshi
authors: T
authors: Imamura
authors: Kumi
authors: K
authors: Kimura
authors: Takeshi
authors: T
authors: Maeda
authors: Kazuya
authors: K
authors: Terasawa
authors: Daiji
authors: D
authors: Kashihara
authors: Kanako
authors: K
authors: Hirano
authors: Taeko
authors: T
authors: Tani
authors: Tomoyuki
authors: T
authors: Takahashi
authors: Satoshi
authors: S
authors: Miyauchi
authors: Go
authors: G
authors: Shioi
authors: Hiroshi
authors: H
authors: Inoue
authors: Gozoh
authors: G
authors: Tsujimoto
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D013851:Thinness / Q000378:metabolism / Q000473:pathology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D005232:Fatty Acids, Volatile; C506481:Ffar2 protein, mouse; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D011493:Protein Kinase C; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
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