Abstract
Non-alcoholic fatty liver disease (NAFLD) is a significant problem because its prevalence is increasing worldwide. Recent animal studies have identified gut microbiota as a potentially important player in the pathogenesis of NAFLD. Previously, we reported that the administration of branched-chain amino acids (BCAAs) reduces hepatic fat accumulation in experimental animal models. This study aimed to clarify how changes in the intestinal microbial flora following the administration of BCAAs affect a high-fat diet (HF)-induced fat accumulation in the liver. We examined whether the administration of BCAAs alters the development of hepatic fat accumulation as well as intestinal microbial flora. The oral administration of BCAAs (3% kcal) induced a significant increase in Ruminococcus flavefaciens (R. flavefaciens) and portal acetic acid levels, and it reduced hepatic fat accumulation in HF-fed rats. In addition, BCAAs reduced the expression of the lipogenesis-related genes FAS and ACC in the liver. Furthermore, we observed that R. flavefaciens is essential for promoting a BCAA-induced reduction in hepatic fat accumulation. These data suggest that BCAA treatment induces the proliferation of intestinal flora including R. flavefaciens and that portal acetic acid synthesized from intestinal flora improves NAFLD by downregulating the expression of FAS and ACC in the liver.
Highlights
We examined whether BCAA supplementation alters the development of hepatic fat accumulation through alterations of intestinal microbial flora
BCAA supplementation induced the proliferation of R. flavefaciens and the increase of portal levels of acetic acids synthesized from R. flavefaciens improves high-fat diet (HF)-induced hepatic fat accumulation by downregulating the expression of FAS and ACC in the liver
We tested supplementation with BCAA at a concentration of 3%, because other studies indicated that 3% BCAA supplementation reduced the amount of hepatic triglyceride accumulation and the expression of inflammatory cytokines in the liver as well as drug-induced liver fibrosis [17,21,22]
Summary
In animals subjected to a high-fat diet, the BCAA-induced alterations in intestinal flora, portal acetic acid levels, AMPK activity, expression of lipogenesis-related enzymes, and hepatic fat accumulation was disappeared due to cellulose deficiency. 1. Effects of BCAA supplementation on the proportion of genus Coprococcus (A) and R. flavefaciens (B), portal acetic acid concentrations (C) and hepatic AMPK activity (D).
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