title: Role of farnesoid X receptor and bile acids in alcoholic liver disease.
abstract: Alcoholic liver disease (ALD) is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR) and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a) and PPARα (peroxisome proliferator-activated receptor alpha) in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, the University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Manley
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, the University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Wenxing
authors.initials: W
authors.lastname: Ding
keywords: 6ECDCA, 6α-ethyl-chenodeoxycholic acid; ADH, alcohol dehydrogenase; AF, activation function; AKT, protein kinase B; ALD, alcoholic liver disease; ALT, alanine aminotransferase; ASBT, apical sodium dependent bile acid transporter; Alcoholic liver disease; Atg, autophagy-related; Autophagy; BAAT, bile acid CoA:amino acid N-acyltransferase; BACS, bile acid CoA synthetase; BSEP, bile salt export pump; Bile acids; CA, cholic acid; CB1R, cannabinoid receptor type 1; CDCA, chenodeoxycholic acid; CREB, cAMP response element-binding protein; CREBH, cAMP response element-binding protein, hepatocyte specific; CRTC2, CREB regulated transcription coactivator 2; CYP, cytochrome P450; DCA, deoxycholic acid; DR1, direct repeat 1; FGF15/19, fibroblast growth factor 15/19; FGFR4, fibroblast growth factor receptor 4; FXR, farnesoid X receptor; Farnesoid X receptor; FoxO3; FoxO3a, forkhead box-containing protein class O3a; GGT, gamma-glutamyltranspeptidase; HCC, hepatocellular carcinoma; IR-1, inverted repeat-1; KO, knockout; LC3, light chain 3; LRH-1, liver receptor homolog 1; LXR, liver X receptor; MRP4, multidrug resistance protein 4; NAD+, nicotinamide adenine dinucleotide; NTCP, sodium taurocholate cotransporting polypeptide; OSTα/β, organic solute transporter α/β; PE, phosphatidylethanolamine; PPARα, peroxisome proliferator-activated receptor alpha; ROS, reactive oxygen species; RXRα, retinoid X receptor-alpha; SHP, small heterodimer partner; SQSTM, sequestome-1; SREBP1, sterol regulatory element-binding protein 1; Sirt1, sirtuin 1; TCA, taurocholic acid; TFEB, transcription factor EB; TLR4, toll-like receptor 4; TUDCA, tauro-ursodeoxycholic acid; UDCA, ursodeoxycholic acid; WAY, WAY-362450; WT, wild type