He Zhenxing, Peng Yong, Duan Wentao, Tian Yunhong, Zhang Jian, Hu Tao, Cai Yu, Feng Yuan, Li Guangming
Department of Hepatopancreatobiliary Surgery, Nanchong Central Hospital, China.
J Toxicol Sci. 2015 Feb;40(1):127-36. doi: 10.2131/jts.40.127.
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.
据报道，阿司匹林可调节脂质代谢。然而，其调节机制尚不清楚。我们目前通过检测AMPK表达、促进AMPK激活，研究了阿司匹林在人肝癌HepG2细胞中对AMP激活蛋白激酶（AMPK）信号通路激活的促进作用。然后我们研究了阿司匹林促进的AMPK信号对HepG2细胞脂肪酸氧化的影响。结果表明，阿司匹林处理并未调节AMPK及其下游靶点乙酰辅酶A羧化酶（ACC）的表达，但通过促进AMPK和ACC的磷酸化激活了AMPK信号通路。有趣的是，阿司匹林的促进作用依赖于细胞酯酶，该酶将阿司匹林催化为水杨酸。此外，激活的AMPK信号通过在mRNA和蛋白质水平上促进肉碱棕榈酰转移酶I（CPT1）和中链酰基辅酶A脱氢酶（MCAD）的表达来促进脂肪酸氧化。因此，我们在本研究中证实，阿司匹林通过上调AMPK信号通路促进脂质氧化。
