Homo sapienslongevity assurance homolog 2 of yeast LAG1 (LASS2) is expressed mostly in human liver. Here, we explored roles of LASS2 in pathogenesis of hepatic steatosis. Hepatocyte-specific LASS2 knockout (LASS2^-/-) mice were generated using Cre-LoxP system. LASS2^-/- and wild-type (WT) mice were fed with chow or high-fat diet (HFD). We found LASS2^-/- mice were resistant to HFD-induced hepatic steatosis and insulin resistance. In HFD-fed mice, LASS2 deficiency significantly inhibited p38 MAPK and ERK1/ERK2 signaling in mouse liver. This effect was mediated by a significant increase of V-ATPase activity and a decrease of ROS level. We also observed that elevated expression of LASS2 in mouse hepatocyte cell line AML12 obviously decreased V-ATPase activity and increased ROS level by activation of p38 MAPK and ERK1/ERK2 signaling. Our findings indicate that LASS2 plays an important role in the pathogenesis of diet-induced hepatic steatosis and is a potential novel target for prevention and intervention of liver diseases.

• PMID: 29626628
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Journal Article | Research Support, Non-U.S. Gov't

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Fan S, Wang Y, Wang C, Jin H, Wu Z, Lu J, Zhang Z, Sun C, Shan Q, Wu D, ... Show all

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