Transcriptomic analysis of liver mRNA from liver-specific Pck1-knockout mice fed with chow diet or NASH diet

To investigate the role of hepatic Pck1 in diet-induced nonalcoholic steatohepatitis (NASH), liver-specific Pck1-knockout mice were developed with Alb-Cre. Wild-type (WT) and Pck1-cKO mice were fed a Chow diet (Research Diets, D12450J: 10% Kcal fat, with tap water) or NASH-inducing diet (Research Diets, D12492: 60% Kcal fat, with drinking water containig 23.1 g/L fructose and 18.9 g/L glucose) for 24 weeks. RNA was extracted from the livers of mice from all treatment groups and used for RNA seqencing. RNA-seq data demonstrated that gluconeogenic enzyme PCK1 deficiency played an important role in the development of NASH. Overall design: Use RNA-sequencing to investigate the role of Pck1 in diet-induced NASH on a transcriptomic level, by comparing the livers of WT and Pck1-cKO mice fed a Chow or NASH diet for 24 weeks using Illumina technology.

为探究肝脏Pck1在饮食诱导的非酒精性脂肪性肝炎（Nonalcoholic Steatohepatitis, NASH）中的调控作用，研究人员通过Alb-Cre重组酶系统构建了肝脏特异性Pck1敲除（Pck1-knockout, cKO）小鼠。将野生型（Wild-type, WT）小鼠与Pck1-cKO小鼠分别饲喂普通维持饲料（Research Diets，货号D12450J：脂肪供能占比10%，饮用水为自来水）或NASH造模饲料（Research Diets，货号D12492：脂肪供能占比60%，饮用水中添加23.1 g/L果糖与18.9 g/L葡萄糖），干预周期为24周。采集所有处理组小鼠的肝脏组织提取总RNA，开展RNA测序（RNA Sequencing）实验。测序结果显示，糖异生关键酶PCK1的缺失在NASH的发生发展过程中发挥了重要调控作用。整体实验设计：本研究从转录组层面探究Pck1在饮食诱导NASH中的功能，采用Illumina测序技术，通过对比饲喂普通饲料与NASH造模饲料24周的WT小鼠与Pck1-cKO小鼠的肝脏转录组数据完成分析。