Adipose‐Specific Lipin‐1 Overexpression Renders Hepatic Ferroptosis and Exacerbates Alcoholic Steatohepatitis in Mice.

Title

Adipose‐Specific Lipin‐1 Overexpression Renders Hepatic Ferroptosis and Exacerbates Alcoholic Steatohepatitis in Mice.

Creator

Zhou Zhou; Ye Ting Jie; Bonavita Gregory; Daniels Michael; Kainrad Noah; Jogasuria Alvin; You Min

Publisher

Hepatology Communications

Date

2019
2019-05

Description

Lipin‐1 is a Mg2+‐dependent phosphatidic acid phosphohydrolase involved in the generation of diacylglycerol during synthesis of phospholipids and triglycerides. Ethanol‐mediated inhibitory effects on adipose‐specific lipin‐1 expression were associated with experimental steatohepatitis in rodents. In the present study, using an adipose‐specific lipin‐1 overexpression transgenic (Lpin1‐Tg) mouse model, we tested a hypothesis that adipose‐specific lipin‐1 overexpression in mice might dampen ethanol‐induced liver damage. Experimental alcoholic steatohepatitis was induced by pair‐feeding ethanol to Lpin1‐Tg and wild‐type (WT) mice using the chronic‐plus‐binge ethanol feeding protocol. Unexpectedly, following the chronic‐plus‐binge ethanol challenge, Lpin1‐Tg mice exhibited much more pronounced steatosis, exacerbated inflammation, augmented elevation of serum liver enzymes, hepatobiliary damage, and fibrogenic responses compared with the WT mice. Mechanistically, overexpression of adipose lipin‐1 in mice facilitated the onset of hepatic ferroptosis, which is an iron‐dependent form of cell death, and subsequently induced ferroptotic liver damage in mice under ethanol exposure. Concurrently, adipose lipin‐1 overexpression induced defective adiponectin signaling pathways in ethanol‐fed mice. Conclusion: We identified ferroptosis as a mechanism in mediating the detrimental effects of adipose‐specific lipin‐1 overexpression in mice under chronic‐plus‐binge ethanol exposure. Our present study sheds light on potential therapeutic approaches for the prevention and treatment of human alcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

Subject

APOPTOSIS; FATTY liver; PROTEIN expression

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

656-669

Issue

5

Volume

3

Citation

Zhou Zhou; Ye Ting Jie; Bonavita Gregory; Daniels Michael; Kainrad Noah; Jogasuria Alvin; You Min, “Adipose‐Specific Lipin‐1 Overexpression Renders Hepatic Ferroptosis and Exacerbates Alcoholic Steatohepatitis in Mice.,” NEOMED Bibliography Database, accessed January 26, 2021, https://neomed.omeka.net/items/show/6403.

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