Aspirin regulates hepatocellular lipid metabolism by activating AMPK signaling pathway

作者:He Zhenxing; Peng Yong*; Duan Wentao; Tian Yunhong; Zhang Jian; Hu Tao; Cai Yu; Feng Yuan; Li Guangming
来源:Journal of Toxicological Sciences, 2015, 40(1): 127-136.
DOI:10.2131/jts.40.127

摘要

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.

  • 出版日期2015-2