Apple Polyphenol Extract Improves High-Fat Diet-Induced Hepatic Steatosis by Regulating Bile Acid Synthesis and Gut Microbiota in C57BL/6 Male Mice

Jun 14, 2021Journal of agricultural and food chemistry

Apple Polyphenol Extract May Improve Fatty Liver Caused by High-Fat Diet by Changing Bile Acid Production and Gut Bacteria in Male Mice

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Abstract

High-dose apple polyphenol extract (APE) at 500 mg/(kg·bw·day) significantly decreased total fecal bile acid contents in C57BL/6 mice.

APE treatment led to reduced levels of primary bile acids, including cholic acid and chenodeoxycholic acid.
The protein levels of hepatic Farnesoid X receptor (FXR) increased, while cholesterol 7α-hydroxylase (CYP7A1) and cholesterol 7α-hydroxylase (CYP27A1) decreased after APE treatment.
Changes in gut microbiota composition were observed, with increased relative abundance of certain bacterial genera.
APE was associated with altered mRNA levels of several transporters involved in cholesterol metabolism in the ileum.
No significant effects on mucosal injury or FXR expression in the jejunum were noted following APE treatment.
No clear interactions between bile acid levels and gut microbiota were identified.

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Our previous study showed that apple polyphenol extract (APE) ameliorated high-fat diet-induced hepatic steatosis in C57BL/6 mice by targeting the LKB1/AMPK pathway; to investigate whether other mechanisms are involved in APE induction of improved hepatic steatosis, especially the roles of bile acid (BA) metabolism and gut microbiota, we conducted this study. Thirty-three C57BL/6 male mice were fed with high-fat diet for 12 weeks and concomitantly treated with sterilized water (CON) or 125 or 500 mg/(kg·bw·day) APE (low-dose APE, LAP; high-dose APE, HAP) by intragastric administration. APE treatment decreased total fecal BA contents, especially fecal primary BA levels, mainly including cholic acid, chenodeoxycholic acid, and muricholic acid. An upregulated hepatic Farnesoid X receptor (FXR) protein level and downregulated protein levels of cholesterol 7α-hydroxylase (CYP7A1) and cholesterol 7α-hydroxylase (CYP27A1) were observed after APE treatment, which resulted in the suppressed BA synthesis. Meanwhile, APE had no significant effects on mucosal injury and FXR expression in the jejunum. APE regulated the diversity of gut microbiota and microbiota composition, characterized by significantly increased relative abundance ofand decreased relative abundance of. Furthermore, APE might affect the reverse cholesterol transport in the ileum, evidenced by the changed mRNA levels of NPC1-like intracellular cholesterol transporter 1 (), liver X receptor (), ATP binding cassette subfamily A member 1 (), and ATP binding cassette subfamily G member 1 (). However, APE did not affect the dihydroxylation and taurine metabolism of BA. The correlation analysis deduced no obvious interactions between BA and gut microbiota. In summary, APE, especially a high dose of APE, could alleviate hepatic steatosis, and the mechanisms were associated with inhibiting BA synthesis and modulating gut microbiota. Akkermansia Lactobacillus Npc1l1Lxr Abca1Abcg1

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Apple Polyphenol Extract Improves High-Fat Diet-Induced Hepatic Steatosis by Regulating Bile Acid Synthesis and Gut Microbiota in C57BL/6 Male Mice

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