Entry
Name
Alcoholic liver disease - Phodopus roborovskii (desert hamster)
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 disease
BRITE hierarchy
Pathway map
Ortholog table
Organism
Phodopus roborovskii (desert hamster) [GN:
prob ]
Gene
127231493 Tirap; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403 ]
127235106 Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729 ]
127225789 Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
127237647 Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
127222971 Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
127216762 Ticam1; TIR domain-containing adapter molecule 1 isoform X1 [KO:K05842 ]
127223236 Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
127233374 Fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
127213032 Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
127234649 Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
127218171 Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793 ]
127219200 Srebf1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197 ]
127235783 Tra2a; transformer-2 protein homolog alpha isoform X1 [KO:K12897 ]
127216002 Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
127233006 Prkab2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199 ]
127235796 Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
127226041 Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200 ]
127226445 Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
127213598 Ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202 ]
127225913 Ppara; peroxisome proliferator-activated receptor alpha [KO:K07294 ]
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 pathway
prob01040 Biosynthesis of unsaturated fatty acids
prob04610 Complement and coagulation cascades
prob04620 Toll-like receptor signaling pathway
KO pathway
LinkDB
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