Regulation of obeticholic acid on serum lipids and bile acids and gut microbiota of non-alcoholic steatohepatitis mice induced by methionine and choline deficiency diet
10.16438/j.0513-4870.2022-0624
- VernacularTitle:奥贝胆酸对MCD饮食诱导的非酒精性脂肪性肝炎小鼠血清脂质与胆汁酸以及肠道菌群的调节作用
- Author:
Wei WANG
1
;
Ping LUO
2
;
Xiao-lei MIAO
2
;
Bei ZENG
1
;
Jun-jun WANG
1
;
Yong CHEN
1
Author Information
1. Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan 430062, China
2. School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China
- Publication Type:Research Article
- Keywords:
obeticholic acid;
nonalcoholic fatty liver disease;
lipidomics;
gut microbiota;
bile acid
- From:
Acta Pharmaceutica Sinica
2022;57(10):3203-3213
- CountryChina
- Language:Chinese
-
Abstract:
The enteric-hepatic axis plays an important role in the occurrence, progression and regression of nonalcoholic fatty liver disease (NAFLD). Obeticholic acid (OCA) is a farnesoid X receptor agonist. In this study, C57BL/6 mice were fed with methionine and choline deficient (MCD) diet for 8 weeks with OCA (6.5 mg·kg-1·d-1) administration by gavage at the same time. The effects of OCA on serum lipid and bile acid metabolomics and ileal gut microbiota (GM) of MCD mice were studied by UPLC-MS and 16S rDNA sequencing. The results were as follows: (1) OCA decreased the activities of alanine aminotransferase and aspartate aminotransferase in serum and the contents of triglyceride (TG) and malondialdehyde in liver, alleviated the accumulation of liver fat and inflammation of MCD mice. OCA down-regulated the contents of 2 eicosanoids (12,13-EPOME, 9,10-EPOME) and 4 free fatty acids (FFA16∶1, FFA18∶1, FFA16∶2, FFA18∶3) and TG (16∶1_16∶1_18∶2) in serum, and up-regulated the content of 1 eicosanoid thromboxanes B3. KEGG differential metabolite pathway analysis showed that fatty acid biosynthesis might be the main way that OCA ameliorated lipid metabolism disorder of MCD mice. OCA reduced the relative abundance of Christensenellaceae and Lachnospiraceae_UCG-006 in the GM of MCD mice; OCA decreased the serum levels of 23-deoxycholic acid, porcine deoxycholic acid, 3-deoxycholic acid, glycine deoxycholic acid, glycine cholic acid, taurine deoxycholic acid, taurocholic acid and taurine. These results suggest that the alleviating effect of OCA on NAFLD of MCD mice may be related to its above-mentioned regulation of the metabolism of the free fatty acids, oxidized lipids, 12α-hydroxylated bile acids and the abundance of GM. The animal experiments were approved by the Experimental Animal Ethics Committee of Hubei University (No. 20220036).
