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

Hidenori Shimizu,Chihiro Ushiroda,Yuki Masujima,Ikuo Kimura,Rina Mizushima,Satsuki Taira,Ryuji Ohue-Kitano

doi:10.1038/s41598-019-53242-x

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.

Highlights

Fermented foods represent a significant portion of human diets with several beneficial effects
The plasma levels of the gut hormones glucagon like peptide-1 (GLP-1) and peptide YY (PYY) were similar among all groups, plasma GLP-1 tended to be slightly higher in the short-chain fatty acids (SCFAs)-fed groups (Fig. 1G,H)
The underlying mechanism of the metabolic benefits provided by dietary SCFA intake, such as with fermented food enriched in SCFAs, are less well understood

Summary

Introduction

Fermented foods represent a significant portion of human diets with several beneficial effects. Dietary fiber is considered to be an essential healthy component of diet, and has been demonstrated to reduce the risk of metabolic diseases such as obesity and diabetes[1,2] These benefits are mainly attributed to the influence of dietary fibers on increasing the levels of short-chain fatty acids (SCFAs), i.e., acetate, propionate, and butyrate, in the colon through gut microbial fermentation[3,4]. The detailed mechanisms underlying the difference in the metabolic benefits conferred by the direct intake of dietary SCFAs (such as through fermented foods) and those provided by gut microbes producing SCFAs from dietary fibers in the colon remain unclear To clarify these effects, in this study, we investigated the SCFAs-mediated systemic effects via circulating plasma upon dietary SCFA intake in a mouse model of high-fat diet (HFD)-induced obesity. We confirmed that dietary SCFA intake such as fermented foods mainly causes improved hepatic metabolic conditions via FFAR3 in HFD-induced obese mice

Methods

Results

Conclusion