Aspirin regulates hepatocellular lipid metabolism by activating AMPK signaling pathway.
Aspirin has been reported to regulate lipid metabolism. However, the mechanism underlying the regulation is not clear. We presently investigated aspirin's promotion of AMP-activated protein kinase (AMPK) pathway activation in human hepatoma HepG2 cells by examining AMPK expression, the promotion of AMPK activation. Then we investigated the influence of aspirin-promoted AMPK signaling on fatty acid oxidation in HepG2 cells. The results demonstrated that aspirin treatment did not regulate the expression of AMPK and its downstream target, Acetyl-Coenzyme A Carboxylase (ACC), but activated the AMPK signaling pathway by promoting the phosphorylation of AMPK and ACC. And, interestingly, the promotion by aspirin is dependent of cellular esterase, which catalyzes aspirin to salicylate. Moreover, the activated AMPK signaling promoted the fatty acid oxidation, by promoting expression of Carnitine palmitoyltransferase I (CPT1) and Medium-Chain Acyl-CoA Dehydrogenase (MCAD) in both mRNA and protein levels. Thus, we confirmed in this study that aspirin promoted lipid oxidation by upregulating the AMPK signaling pathway.
Department of Hepatopancreatobiliary Surgery, Nanchong Central Hospital, China.
Zhenxing
Z
He
Yong
Y
Peng
Wentao
W
Duan
Yunhong
Y
Tian
Jian
J
Zhang
Tao
T
Hu
Yu
Y
Cai
Yuan
Y
Feng
Guangming
G
Li
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D001241:Aspirin / Q000378:metabolism / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008113:Liver Neoplasms / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D005227:Fatty Acids; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D001241:Aspirin