Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00111)
Name
Alcoholic liver disease
ICD
ICD-11: DB94
Full List of Target(s) of This Ferroptosis-centered Disease
Unspecific Target
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Responsed Disease Alcoholic steatohepatitis [ICD-11: DB94]
Responsed Regulator Phosphatidate phosphatase LPIN1 (LPIN1) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hLCs (Liver cells)
In Vivo Model
The 7-8-month-old male Lpin1-Tg mice and their age-matched littermate wildtype (WT) controls were divided into four dietary groups: (1) WT control, (2) WT plus ethanol (identical to the control diet but with 5% weight per volume ethanol added), (3) Lpin1-Tg control, and (4) Lpin1-Tg plus ethanol. All mice were fed a Lieber-DeCarli liquid diet (BioServ, Frenchtown, NJ) for 5days. Ethanol groups were then fed Lieber-DeCarli liquid diets containing 5% weight per volume ethanol for 10 days while control mice were pairfed to their ethanol-fed counterparts for 10 days. At day 11, mice in the ethanol groups were gavaged a single dose of ethanol (5 g/kg body weight, 31.25% ethanol), whereas mice in control groups were gavaged an isocaloric dose of dextrin maltose.

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Response regulation LPIN1 overexpression accelerated iron accumulation, caused lipid peroxidation, reduced GSH and GAPDH, and promoted ferroptotic liver damage in mice after ethanol administration. The study sheds light on potential therapeutic approaches for the prevention and treatment of human alcoholic steatohepatitis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Alcoholic liver disease [ICD-11: DB94]
Responsed Regulator NAD-dependent protein deacetylase sirtuin-1 (SIRT1) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model mLTs (Mouse liver tissues)
In Vivo Model
All female mice were first fed a liquid control diet (Lieber-DeCarli formulation; Bioserv, Flemington, NJ) for 5 days. Ethanol groups were then fed a liquid diet containing 5% v/w ethanol for 10 days, whereas control mice were pair-fed to their ethanol-fed counterparts for 10 days. At day 11, the ethanol groups were given a single oral gavage of ethanol (5 g/kg body weight, 31.25% ethanol), whereas WT or SIRT1iKO control mice were given an isocaloric gavage of dextrin maltose.

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Response regulation Aberrant liver sirtuin 1 (SIRT1), a mammalian NAD-dependent protein deacetylase, is implicated in the pathogenesis of alcoholic liver disease (ALD).The protective effects of intestinal SIRT1 deficiency are mediated, at least partially, by mitigating hepatic ferroptosis.
References
Ref 1 Adipose-Specific Lipin-1 Overexpression Renders Hepatic Ferroptosis and Exacerbates Alcoholic Steatohepatitis in Mice. Hepatol Commun. 2019 Mar 12;3(5):656-669. doi: 10.1002/hep4.1333. eCollection 2019 May.
Ref 2 Intestinal SIRT1 Deficiency Protects Mice from Ethanol-Induced Liver Injury by Mitigating Ferroptosis. Am J Pathol. 2020 Jan;190(1):82-92. doi: 10.1016/j.ajpath.2019.09.012. Epub 2019 Oct 11.