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

By I. Kimura, K. Ozawa, Daisuke Inoue, Takeshi Imamura, K. Kimura, Takeshi Maeda, Kazuya Terasawa, Daiji Kashihara, Kanako Hirano, T. Tani and 5 more. Nature Communications, 2013

1,378 citations recorded by the source corpus.

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. The gut microbiota produces metabolites such as short-chain fatty acids (SCFAs), which can influence the development of obesity. Here Kimura et al.show that SCFAs act via the receptor GPR43, which acts as a sensor for excessive dietary energy and controls body energy utilization as well as metabolic homoeostasis.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/01f26fec62ab37142d8acb5361ba047fa65b9da4

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Citations in the corpus

Dietary lipids, gut microbiota and lipid metabolism (2019, background): “Activation of GPR43 on L-cells increases secretion of glucagon-like peptide-1 (GLP-1) [52, 56] and acetate induces anti-lipolytic activity [57] and improves glucose and lipid metabolism [53] through GPR43 in WAT.”
The role of short-chain fatty acids in immunity, inflammation and metabolism (2020, background): “GPR43(free fatty acid receptor 2, FFAR2) acetate, propionate, butyrate digestive tract epithelial cells, immune system cells, adipocytes in adipose tissue metabolism, inflammation and immunity (Brown et al., 2003; Kimura et al. 2013)”
The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease (2020, background): “They interact with adipose tissue via two G-protein-coupled receptors expressed in adipocytes (Gpr41 and Gpr43); this promotes adipocyte formation and inhibits lipolysis [20].”
The Role of Microbial Amino Acid Metabolism in Host Metabolism (2015, background): “microbiota with host energy homeostasis [20,21].”
Gut Microbiota in Cardiovascular Health and Disease (2017, background): “energy expenditure in liver and muscle through the GPR43 in mouse white adipose tissue.(14) SCFAs can also trigger se-”
Dietary Gut Microbial Metabolites, Short-chain Fatty Acids, and Host Metabolic Regulation (2015, background): “Moreover, in white adipose tissues, FFAR2 activation by SCFAs suppressed adipose-specific insulin signaling, leading to the inhibition of fat accumulation [40].”
Butyrate: A Double-Edged Sword for Health? (2018, background): “…sensitivity and energy expenditure; anti-inflammatory, anti-tumorigenic; expansion and differentiation of Tregs, resolution of arthritis and asthma Kimura et al., 2013 (40); Voltolini et al., 2012 (41); Nøhr et al., 2013 (42); Smith et al., 2013 (43) GPR109A/HCA2 Nicotinate and…”
Short chain fatty acids in human gut and metabolic health. (2020, neutral): “Similarly, Kimura et al. (2013) reported a significant increase in food intake in GPR43-KO mice fed a high fat diet, but not when fed normal chow.”
Acetyl-CoA Synthetase 2 Promotes Acetate Utilization and Maintains Cancer Cell Growth under Metabolic Stress (2015, background): “The acetate concentration in mouse and rat plasma ranges between 0.20 and 0.30 mM (Kimura et al., 2013; Maxwell et al., 2010).”
Blautia—a new functional genus with potential probiotic properties? (2021, background): “Blautia is a common acetic acid producer in the intestine, which may inhibit insulin signaling and fat accumulation in adipocytes by activating the G protein-coupled receptors GPR41 and GPR43, in turn promoting the metabolism of unbound lipids and glucose in other tissues and thus alleviating obesit”
Gut microbiota-derived metabolites as key actors in inflammatory bowel disease (2020, background): “(2019)(28) Ulcerative colitis (53); Crohn’s disease (68); nonIBD controls (34) LC–MS Metagenomics Able to discriminate between IBD and health, less so for IBD subtypes; increases in levels of numerous metabolites, including primary bile acids, amino acids and sphingolipids; decreases in levels of te”
Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism (2016, background): “SCFA also inhibit insulin stimulated lipid accumulation in adipocytes via FFAR 2 signaling, resulting in small more responsive adipocytes which is associated with reduced adipose inflammatory infiltrate.(60,61) Acetate also appears to stimulate leptin secretion in adipocytes.”