Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 120, Issue -, Pages 330-341Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2018.04.003
Keywords
Homo sapiens longevity assurance homolog 2 of yeast LAG1; Nonalcoholic fatty liver disease; MAPK pathway
Funding
- National Natural Science Foundation of China [81672731, 81572311, 81571055]
- National Key Basic Research Program of China (973 Program) [2015CB553905]
- Xuzhou Municipal Science and Technology Innovation Project [KC15SH029]
- Jiangsu Overseas Research & Training Program for University Prominent Young & Middle-aged Teachers and Presidents
- Shanghai Natural Science Foundation of China [16ZR1434700]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Homo sapiens longevity 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.
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