司美格鲁肽调节小鼠糖脂代谢的转录组学分析

Transcriptomic analysis of Semaglutide-related regulation of glucolipid metabolism in db/db mice

目的探究司美格鲁肽对糖脂代谢的调控作用。方法测定db/db小鼠的体重、血糖、血脂、葡萄糖耐量、胰岛素耐量以及组织病理学,考察司美格鲁肽对糖脂代谢的改善作用;对小鼠的肝脏组织进行mRNA测序及结果分析。结果司美格鲁肽可显著改善小鼠的空腹血糖、葡萄糖耐量、胰岛素耐量、甘油三酯、肝脏脂肪变性、糖原沉积及脂滴沉积。转录组学分析显示:司美格鲁肽回调的差异基因有282个,涉及多条糖脂代谢通路;参与糖脂代谢的共有基因Acaca及Fasn均在给药后下调。结论司美格鲁肽能调节核苷磷酸盐代谢过程、脂肪酸生物合成和代谢过程、AMPK信号通路、胰岛素信号通路等多条涉及糖脂代谢的途径,可能是通过下调Acaca及Fasn基因来改善糖脂代谢紊乱。

OBJECTIVE To investigate the effects of Semaglutide on glycolipid metabolism.METHODS Body weight,blood glucose,blood lipid,glucose tolerance,insulin tolerance and histopathology of db/db mice were investigated to evalute the improvement of glucolipid metabolism.The liver tissues were used for mRNA sequencing.RESULTS Semaglutidecould significantly improve fasting blood glucose,glucose tolerance,insulin tolerance,triglyceride,hepatic steatosis,glycogen deposition and lipid deposition of mice.Transcriptomic analysis showed 282 dfferentially expressed genes were regulated back by Semaglutide,which were involved in multiple glycolipid metabolic pathways.Acaca and Fasn were the common genes involved in glycolipid metabolism and both of them were down-regulated.CONCLUSION Semaglutide could regulate nucleoside phosphate metabolism,fatty acid biosynthesis and metabolism,AMPK signaling pathway,insulin signaling pathway and other glycolipid metabolic pathways.The regulation of Semaglutide on glycolipid metabolism might be related to the down-regulation of Acaca and Fasn.