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
Background:
Intermittent fasting (IF) exhibits many health-promoting effects including decreasing hepatic lipids accumulation and regulating gut microbiota metabolism, but its protection against non-alcoholic steatohepatitis (NASH) is still lacking. This study aims to investigate the mechanism of IF alleviates NASH by regulating gut microbiota and bile acids (BAs).
Methods:
Male C57BL/6J mice were fed with a high-fat and high-cholesterol (HFHC) diet for 16 weeks to establish a NASH model. Then the mice continued HFHC feeding and were treated with or without every other day fasting for 10 weeks. Gut microbiota of the cecum are profiled by 16S rRNA gene sequencing. BAs in serum, colon contents, and feces are measured by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.
Results:
IF decreased the body weights, insulin resistance, and hepatic cholesterol accumulation. IF alleviated hepatic steatosis, ballooning, and lobular inflammation. IF elevated the levels of hydrophilic BAs including ursodeoxycholic acid, alpha-muricholic acid, beta-muricholic acid, and tauro-beta-muricholic acid in colon contents and feces. Moreover, IF increased the relative mRNA and protein levels of cholesterol 7α-hydroxylase 1 (CYP7A1) in liver but decreased that of farnesoid-X-receptor (FXR) and fibroblast growth factor 15(FGF15) in ileum.
Conclusions:
IF alleviates NASH by regulating bile acid metabolism and promoting fecal bile acid excretion.
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