Hepatocyte-specific deletion of LASS2 protects against diet-induced hepatic steatosis and insulin resistance.

Hepatocyte-specific deletion of LASS2 protects against diet-induced hepatic steatosis and insulin resistance. Free Radic Biol Med. 2018 Apr 04;: Authors: Fan S, Wang Y, Wang C, Jin H, Wu Z, Lu J, Zhang Z, Sun C, Shan Q, Wu D, Zhuang J, Sheng N, Xie Y, Li M, Hu B, Fang J, Zheng Y, Qin W Abstract 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 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research