mTORC1 Activation is not sufficient to suppress hepatic PPAR-a signalling or ketogenesis. mTORC1 Activation is not sufficient to suppress hepatic PPAR-a signalling or ketogenesis

we examined if the activation of the anabolic program mediated by the activation of the mTorc1 complex in the fasted state could suppress the robust catabolic programing and enhanced Pparα transcriptional of mice with a liver specific defect in mitochondrial long chain fatty acid oxidation (Cpt2L-/- mice). We found that the activation of mTorc1 in the fasted state was not sufficient to repress Pparα responsive genes or ketogenesis. Overall design: Examination of PPAR-a signalling and ketogenesis through knock-out mouse models. Data collected from chow fed, 24-hour fasted male mouse livers.

本研究探究了禁食状态下，由哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）介导的合成代谢程序激活，是否能够抑制线粒体长链脂肪酸氧化存在肝脏特异性缺陷的小鼠（Cpt2L-/-小鼠）的显著分解代谢程序，并增强其过氧化物酶体增殖物激活受体α（PPARα）的转录活性。结果显示，禁食状态下mTORC1的激活不足以抑制PPARα响应基因的表达，亦无法影响生酮作用。整体实验设计：通过基因敲除小鼠模型探究PPARα信号通路与生酮作用。实验数据采集自普通饲料喂养、禁食24小时的雄性小鼠肝脏组织。