Dietary short-chain fatty acid intake improves the hepatic metabolic condition via FFAR3

Abstract

Fermented foods represent a significant portion of human diets with several beneficial effects. Foods produced by bacterial fermentation are enriched in short-chain fatty acids (SCFAs), which are functional products of dietary fibers via gut microbial fermentation. In addition to energy sources, SCFAs also act as signaling molecules via G-protein coupled receptors such as FFAR2 and FFAR3. Hence, dietary SCFAs in fermented foods may have a direct influence on metabolic functions. However, the detailed mechanism by dietary SCFAs remains unclear. Here, we show that dietary SCFAs protected against high-fat diet-induced obesity in mice in parallel with increased plasma SCFAs without changing cecal SCFA or gut microbial composition. Dietary SCFAs suppressed hepatic weight and lipid synthesis. These effects were abolished in FFAR3-deficient mice but not FFAR2-deficient. Thus, SCFAs supplementation improved hepatic metabolic functions via FFAR3 without influencing intestinal environment. These findings could help to promote the development of functional foods using SCFAs.

Effects of β-glucan Rich Barley Flour on Glucose and Lipid Metabolism in the Ileum, Liver, and Adipose Tissues of High-Fat Diet Induced-Obesity Model Male Mice Analyzed by DNA Microarray

“…We found that several SCFAs negatively correlated with the expression levels of mRNA involved in hepatic lipid synthesis and degradation. Our results are supported by previous studies in which SCFAs suppressed lipid synthesis in the liver [ 46 ] and the expression levels of FAS and carbohydrate-response element-binding protein (Chrebp) were lower in mice fed SCFAs compared with mice fed cellulose [ 47 ]. Based on these results, we suggest that SCFAs alter the expression of genes related to lipid metabolism in the cecum.…”

Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism

“…In another study, FFAR3 signalling mediated glucose-stimulated insulin secretion through the Gi/o-sensitive pathway, and FFAR3 signalling negatively mediates insulin secretion [ 64 ]. Moreover, exogenous supplementation of SCFAs can reduce liver fat content and improve liver metabolism by inhibiting the expression of lipid synthesis genes in FFAR3-deficient mice liver but not FFAR2-deficient [ 65 ].…”

Manipulation of Alcohol and Short-Chain Fatty Acids in the Metabolome of Commensal and Virulent Klebsiella pneumoniae by Linolenic Acid

“…SCFAs, especially acetate, can significantly reverse ROS production in mesangial cells, and this can be recapitulated by treatment with an agonist for the cognate G protein-coupled receptor (GPCR), free fatty acid receptor 2 (FFAR2) [27]. Furthermore, dietary SCFA (acetate, propionate, and butyrate) intake improves liver metabolism by acting on FFAR3 [28]. Although the literature has indicated that increased levels of propionate promote liver gluconeogenesis in mice [29], results from a clinical study illustrated that propionate supplementation remarkably reduced intrahepatocellular lipid content [30].…”