AMPKα1 overexpression alleviates the hepatocyte model of nonalcoholic fatty liver disease via inactivating p38MAPK pathway.
Nonalcoholic fatty liver disease (NAFLD) has a wide spectrum of liver damage with a worldwide prevalence of almost 20%. AMP-activated protein kinase α1 (AMPKα1) is an energy sensor that plays a key role in regulating lipid metabolism of the liver. This study explores the role of AMPKα1 overexpression in a steatotic hepatocyte model. The results displayed that the AMPKα1 overexpression suppressed lipid accumulation in the cytoplasm, decreased triglyceride levels, maintained the survival of steatotic hepatocyte model with decreased cell apoptosis and increased survival rate. Besides, AMPKα1 overexpression promoted the expression of lipid catabolism-related genes, reduced the level of anabolism-related genes, alleviated the inflammatory response by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. Moreover, AMPKα1 overexpression could inhibit the activation of p38 mitogen-activated protein kinase (p38MAPK). Finally, Anisomycin, a frequently-used activator of p38MAPK, reversed the inhibitory effect of pc-AMPKα1 on the expression of p-p38MAPK, suggesting that AMPKα1 overexpression alleviates inflammatory response through the inactivation of p38MAPK. These results indicated that AMPKα1 may serve as a novel target for treatment of NAFLD.
Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710003, Shaanxi, PR China; The Second Section, Department of Neonatology, Xi'an Children's Hospital, Xi'an, 710003, Shaanxi, PR China.
Hong-Ai
HA
Zhang
Department of Child Health Care, Xi'an Maternal and Child Health Hospital, Xi'an, 710003, Shaanxi, PR China.
Xiao-Yan
XY
Yang
Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710003, Shaanxi, PR China. Electronic address: yanfengxiaocn@163.com.
Yan-Feng
YF
Xiao
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D020935:MAP Kinase Signaling System; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
AMPKα1; Inflammatory cytokines; Metabolism; NAFLD; p38MAPK