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Review
. 2020 Apr;9(2):152-169.
doi: 10.21037/hbsn.2019.09.03.

VSports - Bile acid-based therapies for non-alcoholic steatohepatitis and alcoholic liver disease

Affiliations
Review

Bile acid-based therapies for non-alcoholic steatohepatitis and alcoholic liver disease

Tiangang Li et al. Hepatobiliary Surg Nutr. 2020 Apr.

Abstract

Bile acids are synthesized from cholesterol only in hepatocytes. Bile acids circulating in the enterohepatic system act as physiological detergent molecules to help solubilize biliary cholesterol and emulsify dietary lipids and fat-soluble vitamins in small intestine VSports手机版. Bile acids are signaling molecules that activate nuclear receptor farnesoid X receptor (FXR) and cell surface G protein-coupled receptor TGR5. FXR critically regulates bile acid homeostasis by mediating bile acid feedback inhibition of hepatic bile acid synthesis. In addition, bile acid-activated cellular signaling pathways regulate metabolic homeostasis, immunity, and cell proliferation in various metabolically active organs. In the small and large intestine, gut bacterial enzymes modify primary bile acids to generate secondary bile acids to help shape the bile acid pool composition and subsequent biological effects. In turn, bile acids exhibit anti-microbial properties and modulate gut microbiota to influence host metabolism and immunity. Currently, bile acid-based therapies including systemic and intestine-restricted FXR agonists, TGR5 agonists, fibroblast growth factor 19 analogue, intestine FXR antagonists, and intestine apical sodium-bile acid transporter (ASBT) inhibitors have been developed as promising treatments for non-alcoholic steatohepatitis (NASH). These pharmacological agents improved metabolic and inflammatory disorders via distinct mechanisms of action that are subjects of extensive research interest. More recently, human and experimental alcoholic liver disease (ALD) has been associated with disrupted bile acid homeostasis. In additional, new findings showed that targeting bile acid metabolism and signaling may be promising therapeutic approaches for treating ALD. .

Keywords: Bile acid; alcoholic liver disease (ALD); farnesoid X receptor (FXR); microbiota; non-alcoholic steatohepatitis (NASH). V体育安卓版.

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Conflict of interest statement

Conflicts of Interest: The series “Gut Microbiome and Liver Disease” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare VSports最新版本.

Figures

Figure 1
Figure 1
The biochemical property of bile acids. (A) Cholesterol and cholic acid structure. Compared to cholesterol, cholic acid has hydroxyl groups at the C7 and C12 position, a shortened and oxidized sterol side chain, and C5-C6 double bond saturation; (B) illustration of glycine and taurine conjugated bile acids. Bile acids conjugation is mediate by the bile acid CoA ligase (BAL) and the bile acid CoA: amino acid N-acetyltransferase (BAAT).
Figure 2
Figure 2
Bile acid synthesis pathways. The classic and alternative bile acid synthesis pathways and major enzymes involved in bile acid synthesis. Major enzymes in the pathways are shown. CYP7A1 is the rate-limiting enzyme in the classic bile acid synthesis pathway. In humans, hepatic bile acid synthesis produces the primary bile acid cholic acid and CDCA. In the small and large intestine, primary bile acids can be deconjugated by BSH and then modified by bacterial enzymes to produce secondary bile acids. Bacterial 7α-dehydroxylase removes C7 hydroxyl group to convert cholic acid to DCA and CDCA to LCA. Other secondary bile acids also exist at very low abundance in the bile acid pool. CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; LCA, lithocholic acid; BSH, bile salt hydrolases.

References

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