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Turnover of Bile Acids in Liver, Serum and Caecal Content by High-Fat Diet Feeding Affects Hepatic Steatosis in Rats

29 Pages Posted: 1 Feb 2019

See all articles by Yingyue Tang

Yingyue Tang

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Jingyi Zhang

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Jing Li

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Xiaohong Lei

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Dongke Xu

Fudan University - Department of Physiology and Pathophysiology

Yang Wang

Shanghai Jiao Tong University (SJTU)

Chunmin Li

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Xiaobo Li

Fudan University - Department of Physiology and Pathophysiology

Yimin Mao

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

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Abstract

Background: Bile acids (BAs) participate in lipid absorption and serve as metabolic regulatory factors in gut-liver communication. To date, there are no studies on the systemic patterns of BAs in the serum, liver, and gut in the same non-alcoholic fatty liver disease (NAFLD) model.

Methods: A targeted metabolomics approach and 16S rRNA sequencing were used to identify the profile of BAs and connection between BAs and microbiota. The role and mechanism of altered BAs on hepatic steatosis were investigated.

Findings: In the liver, the composition of taurocholic acid (TCA) was increased, but taurohyodeoxycholic acid (THDCA) and ursodeoxycholic acid (UDCA) were decreased. In the gut, the deconjugated form of TCA (cholic acid (CA)) was increased, while the deconjugated forms of THDCA (αhyodeoxycholic acid (HDCA)) and ω-muricholic acid (ωMCA) were decreased. In the serum, the composition of TCA was increased, while both HDCA and THDCA were decreased. THDCA but not TCA induced the gene expression of apolipoprotein, bile secretion-related proteins, and cytochrome P450 family but suppressed the expression of inflammatory response genes in steatotic hepatocytes by RNAseq analysis. THDCA ameliorated neutral lipid accumulation and improved insulin sensitivity in primary rat hepatocytes. The decreased HDCA correlated with Bacteroidetes, while the decreased ωMCA correlated with Saccharibacteria and inversely correlated with Firmicutes and Proteobacteria. CA correlated with Firmicutes and Proteobacteria but inversely correlated with Cyanobacteria and Elusimicrobia.

Interpretation: BAs profiles in the serum, liver and caecal content were altered in a rat NAFLD model, which may affect hepatic lipid accumulation and correlate with gut dysbiosis.

Funding Statement: This work was supported by the Major Project of National Twelfth Five Plan (2012ZX09303-001); the Major Project of National Thirteenth Five Plan (2017ZX09304016); the National Natural Science Foundation of China (NSFC 81670524, NSFC 31771308); the Shanghai Shenkang Hospital Development Center (16CR2009A); and Clinical Research Centre at Shanghai Jiao Tong University School of Medicine (DLY201607).

Declaration of Interests: The authors declared that they had no conflicts of interest to this work.

Ethics Approval Statement: All animal experiments were performed following the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and were permitted by the Institutional Animal Care and Use Committee of RenJi Hospital, School of Medicine, Shanghai Jiao Tong University.

Keywords: Non-alcoholic fatty liver disease; Bile acid; Gut microbiota; TCA; THDCA

Suggested Citation

Tang, Yingyue and Zhang, Jingyi and Li, Jing and Lei, Xiaohong and Xu, Dongke and Wang, Yang and Li, Chunmin and Li, Xiaobo and Mao, Yimin, Turnover of Bile Acids in Liver, Serum and Caecal Content by High-Fat Diet Feeding Affects Hepatic Steatosis in Rats (January 25, 2019). Available at SSRN: https://ssrn.com/abstract=3324727

Yingyue Tang

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Shanghai
China

Jingyi Zhang

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Shanghai
China

Jing Li

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Shanghai
China

Xiaohong Lei

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Shanghai
China

Dongke Xu

Fudan University - Department of Physiology and Pathophysiology

Shanghai, 200032
China

Yang Wang

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Chunmin Li

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology

Shanghai
China

Xiaobo Li

Fudan University - Department of Physiology and Pathophysiology ( email )

Shanghai, 200032
China

Yimin Mao (Contact Author)

Shanghai Jiao Tong University (SJTU) - Division of Gastroenterology and Hepatology ( email )

Shanghai
China

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