Intermittent fasting alleviates non-alcoholic steatohepatitis by regulating bile acid metabolism and promoting fecal bile acid excretion in high-fat and high-cholesterol diet fed mice.

Abstract

Intermittent fasting (IF) has a protective role across a wide range of chronic disorders, including obesity, diabetes and cardiovascular disease, but its protection against non-alcoholic steatohepatitis (NASH) is still lacking. This study sought to investigate how IF alleviates NASH by regulating gut microbiota and bile acids (BAs) composition. Male C57BL/6 mice were fed a high-fat and high-cholesterol (HFHC) diet for 16 weeks to establish a NASH model. Mice then continued HFHC feeding and were treated with or without every other day fasting for 10 weeks. Hepatic pathology was assessed using hematoxylin-eosin staining. Gut microbiota of the cecum were profiled using 16S rRNA gene sequencing and the levels of BAs in serum, colon contents, and feces were measured using UPLC-MS/MS. Results indicated that IF significantly decreased murine body weight, insulin resistance, hepatic steatosis, ballooning, and lobular inflammation. IF reshaped the gut microbiota, reduced the accumulation of serum BAs, and increased total colonic and fecal BAs. Moreover, IF increased the expression of cholesterol 7α-hydroxylase 1 in liver, but decreased the expressions of both farnesoid-X-receptor and fibroblast growth factor 15 in the ileum. IF alleviated NASH by regulating bile acid metabolism and promoting fecal bile acid excretion. This article is protected by copyright. All rights reserved.