Xu Yanyong, Zhu Yingdong, Bawa Fathima Cassim, Hu Shuwei, Pan Xiaoli, Yin Liya, Zhang Yanqiao
Department of Integrative Medical Sciences Northeast Ohio Medical University Rootstown OH.
Hepatol Commun. 2020 Feb 20;4(4):527-539. doi: 10.1002/hep4.1487. eCollection 2020 Apr.
Rodents have at least five carboxylesterase 1 () genes, whereas there is only one gene in humans, raising the question as to whether human and mouse genes share the same functions. In this study, we investigate the role of human CES1 in the development of steatohepatitis or dyslipidemia in C57BL/6 mice. Hepatocyte-specific expression of human CES1 prevented Western diet or alcohol-induced steatohepatitis and hyperlipidemia. Mechanistically, human CES1 induced lipolysis and fatty acid oxidation, leading to a reduction in hepatic triglyceride and free fatty acid levels. Human CES1 also reduced hepatic-free cholesterol levels and induced low-density lipoprotein receptor. In addition, human CES1 induced hepatic lipoprotein lipase and apolipoprotein C-II expression. Hepatocyte-specific overexpression of human CES1 attenuates diet-induced steatohepatitis and hyperlipidemia.
啮齿动物至少有五个羧酸酯酶1（）基因，而人类只有一个基因，这就引发了一个问题，即人类和小鼠基因是否具有相同的功能。在本研究中，我们调查了人类CES1在C57BL/6小鼠脂肪性肝炎或血脂异常发展中的作用。人类CES1在肝细胞中的特异性表达可预防西式饮食或酒精诱导的脂肪性肝炎和高脂血症。从机制上讲，人类CES1诱导脂肪分解和脂肪酸氧化，导致肝脏甘油三酯和游离脂肪酸水平降低。人类CES1还降低了肝脏游离胆固醇水平并诱导了低密度脂蛋白受体。此外，人类CES1诱导肝脏脂蛋白脂肪酶和载脂蛋白C-II的表达。人类CES1在肝细胞中的特异性过表达减轻了饮食诱导的脂肪性肝炎和高脂血症。
