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Dietary acetic acid suppress high-fat diet-induced obesity in mice by altering taurine conjugated bile acids metabolism.

ABSTRACT: Vinegar is widely used in Chinese diet as a traditional condiment, and its functional component acetic acid has been proposed to prevent obesity, while its mechanism is still unclear. Bile acids (BAs) have been reported to have a protective effect on obesity. This study demonstrated that high-fat diet induced obesity (DIO) seriously disturbed BAs balance by significantly decreasing hepatic BAs synthesis and increasing fecal BAs excretion. However, acetate supplemented in the high-fat diet can restore BAs balance by mainly promoting hepatic taurine conjugated BAs (tauro-BAs) synthesis and decreasing fecal tauro-BAs excretion. The tauro-BAs, as the antagonists, inhibited the intestinal-liver farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15)-FGF receptor 4 (FGFR4) signaling pathway, and negatively regulated the production of hepatic BAs. Present study provided important clues for further investigation of the mechanism of acetic acid inhibiting DIO.

SUBMITTER: Wang R

PROVIDER: S-EPMC9596597 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Dietary acetic acid suppress high-fat diet-induced obesity in mice by altering taurine conjugated bile acids metabolism.

Wang Rui R Fan Xiuqin X Lu Yuanyuan Y Chen Dawei D Zhao Yunfeng Y Qi Kemin K

Current research in food science 20221019

Vinegar is widely used in Chinese diet as a traditional condiment, and its functional component acetic acid has been proposed to prevent obesity, while its mechanism is still unclear. Bile acids (BAs) have been reported to have a protective effect on obesity. This study demonstrated that high-fat diet induced obesity (DIO) seriously disturbed BAs balance by significantly decreasing hepatic BAs synthesis and increasing fecal BAs excretion. However, acetate supplemented in the high-fat diet can re ...[more]

PMID: 36312883

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Project description:This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in this process. A total of 192 one-day-old Arbor Acres (AA) commercial male broilers were randomly divided into 4 groups and treated with the following diet: a basal-fat diet (BFD), a basal-fat diet plus bile acids (BFD + BAs), an HFD, and a high-fat diet plus bile acids (HFD + BAs). Bile acids were supplemented at the early growth stage (3-7 d), middle stage (17-21 d), and late stage (31-35 d). Results showed that BAs treatment had a significant effect on body weight on 14 d and 35 d, and increased the breast muscle weight and its index, but decreased the liver weight and abdominal fat weight on 35 d (P < 0.05). The supplementation of BAs significantly improved the serum lipid profile and decreased the level of triglycerides (TG), total cholesterol (TCHO), and nonesterified fatty acids (NEFA) on 35 d (P < 0.05). Dietary BAs supplementation significantly alleviated the hepatic TG deposition induced by HFD (P < 0.05), which was accompanied by upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) gene expression (P < 0.05). Moreover, the expression levels of hepatic gene adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor α (PPARα), and apolipoprotein B (APOB) were greatly increased by BAs treatment. The analysis of 16S rRNA sequencing showed that the microbial diversity of the cecal digesta was increased by BAs in broilers with elevated abundances of Firmicutes, Lactobacillus, Anaerostipes, Sellimonas, and CHKCI002 and decreased abundances of Barnesiella and Akkermansia genus (P < 0.05). Hepatic TG content was positively correlated with the abundance of Oscillospiraceae, but it was negatively correlated with the abundance of Lactobacillus in cecal digesta (P < 0.05). These results indicate that dietary BAs can improve growth performance and alleviate fatty liver disease induced by an HFD via modulating gut microbiota in broilers.

Project description:BackgroundSignificantly elevated serum and hepatic bile acid (BA) concentrations have been known to occur in patients with liver fibrosis. However, the roles of different BA species in liver fibrogenesis are not fully understood.MethodsWe quantitatively measured blood BA concentrations in nonalcoholic steatohepatitis (NASH) patients with liver fibrosis and healthy controls. We characterized BA composition in three mouse models induced by carbon tetrachloride (CCl4), streptozotocin-high fat diet (STZ-HFD), and long term HFD, respectively. The molecular mechanisms underlying the fibrosis-promoting effects of BAs were investigated in cell line models, a 3D co-culture system, and a Tgr5 (HSC-specific) KO mouse model.FindingsWe found that a group of conjugated 12α-hydroxylated (12α-OH) BAs, such as taurodeoxycholate (TDCA) and glycodeoxycholate (GDCA), significantly increased in NASH patients and liver fibrosis mouse models. 12α-OH BAs significantly increased HSC proliferation and protein expression of fibrosis-related markers. Administration of TDCA and GDCA directly activated HSCs and promoted liver fibrogenesis in mouse models. Blockade of BA binding to TGR5 or inhibition of ERK1/2 and p38 MAPK signaling both significantly attenuated the BA-induced fibrogenesis. Liver fibrosis was attenuated in mice with Tgr5 depletion.InterpretationIncreased hepatic concentrations of conjugated 12α-OH BAs significantly contributed to liver fibrosis via TGR5 mediated p38MAPK and ERK1/2 signaling. Strategies to antagonize TGR5 or inhibit ERK1/2 and p38 MAPK signaling may effectively prevent or reverse liver fibrosis.FundingsThis study was supported by the National Institutes of Health/National Cancer Institute Grant 1U01CA188387-01A1, the National Key Research and Development Program of China (2017YFC0906800); the State Key Program of National Natural Science Foundation (81430062); the National Natural Science Foundation of China (81974073, 81774196), China Postdoctoral Science Foundation funded project, China (2016T90381), and E-institutes of Shanghai Municipal Education Commission, China (E03008).

Dataset Information

Dietary acetic acid suppress high-fat diet-induced obesity in mice by altering taurine conjugated bile acids metabolism.

Publications

Dietary acetic acid suppress high-fat diet-induced obesity in mice by altering taurine conjugated bile acids metabolism.

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