Fig. 1. Gut microbiota regulation of host metabolism. Undigested carbohydrates are fermented by gut microbiota into short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate. SCFAs affect the host metabolism in several ways. SCFAs can signal through G protein-coupled receptor 41 (GPR41) on enteroendocrine cells, inducing the secretion of peptide YY (PYY) which inhibits gut motility, increases intestinal transit rate, and reduces the harvest of energy from the diet. Engagement of GPR43 by SCFAs has been shown to trigger the glucogon-like peptide 1 (GLP-1) to increase insulin sensitivity. Gut microbiota efficiently suppresses fasting-induced adipose factor (Fiaf) expression in the ileum, which inhibits lipoprotein lipase (LPL) activity and fat storage in white adipose tissue. SCFAs-mediated activation of GPR43 results in suppression of insulin signaling in the adipose tissue and subsequent prevention of fat accumulation. SCFAs also activate intestinal gluconeogenesis (IGN) via a gut-brain neural circuit, which can improve glucose metabolism and reduce food intake. VLDL, very low density lipoprotein; FFA, free fatty acid.