Entry Name Alcoholic liver disease - Delphinapterus leucas (beluga whale)
Description Alcoholic liver disease (ALD) refers to the damages to the liver and its functions due to alcohol overconsumption. It ranges from simple steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. Alcohol consumption promotes liver inflammation by increasing the translocation of gut-derived endotoxins to the portal circulation and activating Kupffer cells to produce TNF-alpha through the LPS/Toll like receptor (TLR) 4 pathways. TNF-alpha induces hepatocellular damage. When alcohol intake is chronic and heavy, steatosis is caused via generation of acetaldehyde, reactive oxygen species (ROS) and ER stress. ROS inhibits key hepatic transcriptional regulators such as AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR-alpha), which are responsible for fatty acid oxidation and export via ACC and CPT-1. The blockade of AMPK also leads to overexpression of SREBP-1, resulting in an increase of de novo lipogenesis. Moreover, excessive intracellular ROS production induced by ethanol and its metabolite have a critical role in ethanol-induced apoptosis, which may be the critical process in the exacerbation of ALD. It is inferred that the apoptotic signal derived from ROS that was produced by NOX, is mainly transduced through the JNK and p38 MAPK pathways.
Class Human Diseases; Endocrine and metabolic diseaseBRITE hierarchy
Pathway map Disease H02516 Alcoholic liver disease
Organism Delphinapterus leucas (beluga whale) [GN:
dle ]
Gene 111164350 MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729 ]
111165480 TIRAP; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403 ]
111166813 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
111167734 SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197 ]
111168401 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793 ]
111170265 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
111171000 PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202 ]
111172089 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
111172519 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
111174056 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
111176617 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
111176656 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
111176718 C3AR1; C3a anaphylatoxin chemotactic receptor isoform X1 [KO:K04009 ]
111179110 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
111179654 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
111179952 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
111180688 C5AR1; C5a anaphylatoxin chemotactic receptor 1 isoform X1 [KO:K04010 ]
111182061 TRA2A; transformer-2 protein homolog alpha isoform X1 [KO:K12897 ]
111185665 ACADVL; very long-chain specific acyl-CoA dehydrogenase, mitochondrial isoform X1 [KO:K09479 ] [EC:1.3.8.9 ]
111186464 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403 ]
111186471 PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294 ]
111186924 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
Compound C22381 Reactive oxygen species
Reference Authors Louvet A, Mathurin P
Title Alcoholic liver disease: mechanisms of injury and targeted treatment.
Journal Reference Authors Gao B, Bataller R
Title Alcoholic liver disease: pathogenesis and new therapeutic targets.
Journal Reference Authors Magdaleno F, Blajszczak CC, Nieto N
Title Key Events Participating in the Pathogenesis of Alcoholic Liver Disease.
Journal Reference Authors Lucey MR, Mathurin P, Morgan TR
Title Alcoholic hepatitis.
Journal Reference Authors Nagy LE, Ding WX, Cresci G, Saikia P, Shah VH
Title Linking Pathogenic Mechanisms of Alcoholic Liver Disease With Clinical Phenotypes.
Journal Reference Authors Fujii H, Kawada N
Title Fibrogenesis in alcoholic liver disease.
Journal Reference Authors Kim MS, Ong M, Qu X
Title Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?
Journal Reference Authors You M, Crabb DW
Title Recent advances in alcoholic liver disease II. Minireview: molecular mechanisms of alcoholic fatty liver.
Journal Reference Authors Nagy LE
Title The Role of Innate Immunity in Alcoholic Liver Disease.
Journal Alcohol Res 37:237-50 (2015)
Reference Authors Gao B, Seki E, Brenner DA, Friedman S, Cohen JI, Nagy L, Szabo G, Zakhari S
Title Innate immunity in alcoholic liver disease.
Journal Reference Authors Wang HJ, Gao B, Zakhari S, Nagy LE
Title Inflammation in alcoholic liver disease.
Journal Reference Authors McCullough RL, McMullen MR, Sheehan MM, Poulsen KL, Roychowdhury S, Chiang DJ, Pritchard MT, Caballeria J, Nagy LE
Title Complement Factor D protects mice from ethanol-induced inflammation and liver injury.
Journal Reference Authors Kawaratani H, Tsujimoto T, Douhara A, Takaya H, Moriya K, Namisaki T, Noguchi R, Yoshiji H, Fujimoto M, Fukui H
Title The effect of inflammatory cytokines in alcoholic liver disease.
Journal Reference Authors Szabo G, Bala S
Title Alcoholic liver disease and the gut-liver axis.
Journal Reference Authors Kawaratani H, Moriya K, Namisaki T, Uejima M, Kitade M, Takeda K, Okura Y, Kaji K, Takaya H, Nishimura N, Sato S, Sawada Y, Seki K, Kubo T, Mitoro A, Yamao J, Yoshiji H
Title Therapeutic strategies for alcoholic liver disease: Focusing on inflammation and fibrosis (Review).
Journal Reference Authors Roh YS, Seki E
Title Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis.
Journal Reference Authors Rogers CQ, Ajmo JM, You M
Title Adiponectin and alcoholic fatty liver disease.
Journal Reference Authors You M, Jogasuria A, Lee K, Wu J, Zhang Y, Lee YK, Sadana P
Title Signal Transduction Mechanisms of Alcoholic Fatty Liver Disease: Emer ging Role of Lipin-1.
Journal Reference Authors You M, Jogasuria A, Taylor C, Wu J
Title Sirtuin 1 signaling and alcoholic fatty liver disease.
Journal Reference Authors Ren R, Wang Z, Wu M, Wang H
Title Emerging Roles of SIRT1 in Alcoholic Liver Disease.
Journal Reference Authors Purohit V, Gao B, Song BJ
Title Molecular mechanisms of alcoholic fatty liver.
Journal Reference Authors Hyun J, Han J, Lee C, Yoon M, Jung Y
Title Pathophysiological Aspects of Alcohol Metabolism in the Liver.
Journal Reference Authors Combs TP, Marliss EB
Title Adiponectin signaling in the liver.
Journal Reference Authors Ceni E, Mello T, Galli A
Title Pathogenesis of alcoholic liver disease: role of oxidative metabolism.
Journal Reference Authors Kong LZ, Chandimali N, Han YH, Lee DH, Kim JS, Kim SU, Kim TD, Jeong DK, Sun HN, Lee DS, Kwon T
Title Pathogenesis, Early Diagnosis, and Therapeutic Management of Alcoholic Liver Disease.
Journal Reference Authors Ohashi K, Pimienta M, Seki E
Title Alcoholic liver disease: A current molecular and clinical perspective.
Journal Reference Authors You M, Arteel GE
Title Effect of ethanol on lipid metabolism.
Journal Reference Authors Bi L, Jiang Z, Zhou J
Title The role of lipin-1 in the pathogenesis of alcoholic fatty liver.
Journal Reference Authors Ali H, Assiri MA, Shearn CT, Fritz KS
Title Lipid peroxidation derived reactive aldehydes in alcoholic liver disease.
Journal Reference Authors Yin H, Hu M, Liang X, Ajmo JM, Li X, Bataller R, Odena G, Stevens SM Jr, You M
Title Deletion of SIRT1 from hepatocytes in mice disrupts lipin-1 signaling and aggravates alcoholic fatty liver.
Journal Reference Authors Stickel F, Hampe J
Title Genetic determinants of alcoholic liver disease.
Journal Reference Authors Yang CF, Zhong YJ, Ma Z, Li L, Shi L, Chen L, Li C, Wu D, Chen Q, Li YW
Title NOX4/ROS mediate ethanolinduced apoptosis via MAPK signal pathway in L02 cells.
Journal Related dle01040 Biosynthesis of unsaturated fatty acids
dle04610 Complement and coagulation cascades
dle04620 Toll-like receptor signaling pathway
dle04920 Adipocytokine signaling pathway
KO pathway
