| First Author | Fan S | Year | 2018 |
| Journal | Free Radic Biol Med | Volume | 120 |
| Pages | 330-341 | PubMed ID | 29626628 |
| Mgi Jnum | J:279703 | Mgi Id | MGI:6364141 |
| Doi | 10.1016/j.freeradbiomed.2018.04.003 | Citation | Fan S, et al. (2018) Hepatocyte-specific deletion of LASS2 protects against diet-induced hepatic steatosis and insulin resistance. Free Radic Biol Med 120:330-341 |
| abstractText | 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. |
