AMPK-dependent modulation of hepatic lipid metabolism by nesfatin-1

作者：Yin, Yue; Li, Ziru; Gao, Ling; Li, Yin; Zhao, Jing; Zhang, Weizhen^*

来源：Molecular and Cellular Endocrinology, 2015, 417(C): 20-26.

DOI：10.1016/j.mce.2015.09.006

• X/A like cells
• NAFLD
• Hepatocytes
• Triglyceride
• AMPK

The aim of this study was to characterize the mechanism by which peripheral nesfatin-1 regulates hepatic lipid metabolism. Continuous peripheral infusion of nesfatin-1 reduced adiposity and plasma levels of triglyceride and cholesterol. In mice fed high fat diet, peripheral nesfatin-1 significantly decreased hepatic steatosis measured by triglyceride content and oil red staining area and diameter. These alterations were associated with a significant reduction in lipogenesis-related transcriptional factors PPAR gamma and SREBP1, as well as rate-limited enzyme genes such as acaca, fasn, gpam, dgat1 and dgat2. In primary hepatocytes, nesfatin-1 inhibited both basal and oleic acid stimulated triglyceride accumulation, which was accompanied by a decrement in lipogenesis-related genes and an increase in beta-oxidation-related genes. In cultured hepatocytes, nesfatin-1 increased levels of AMPK phosphorylation. Inhibition of AMPK by compound C blocked the reduction of triglyceride content elicited by nesfatin-1. Our studies demonstrate that nesfatin-1 attenuates lipid accumulation in hepatocytes by an AMPK-dependent mechanism.

• 出版日期2015-12-5
• 单位北京大学