Role of Cyp2b in diet-induced nonalcoholic steatohepatitis (NASH)

To investigate the role of hepatic CYP2B in diet-induced nonalcoholic steatohepatitis (NASH), a Cyp2b triple knockout mouse lacking Cyp2b9, Cyp2b10, and Cyp2b13 was developed using CRISPER/Cas9. Wildtype (WT) and Cyp2b-null mice were fed a normal diet (ND) or a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD), containing 0.1% methionine and 62% fat for 8 weeks. RNA was extracted from the livers of female and male mice from all treatment groups and used for RNA seqencing. RNAseq data demonstrated that a lack of Cyp2b was protective in female but more harmful in male mice. Hepatic gene expression revealed a higher number of phase I-III xenobiotic metabolism and inflammatory response genes were down-regulated in CDAHFD-fed WT female and Cyp2b-null male mice. Use RNA-sequencing to investigate the role of Cyp2b in diet-induced NASH on a transcriptomic level, by comparing the livers of WT and Cyp2b-null mice fed a CDAHFD for 8 weeks using Illumina technology.为探究肝CYP2B在饮食诱导的非酒精性脂肪性肝炎（Nonalcoholic Steatohepatitis，NASH）中的作用，研究人员利用CRISPER/Cas9技术构建了同时缺失Cyp2b9、Cyp2b10及Cyp2b13的Cyp2b三基因敲除小鼠。将野生型（WT）与Cyp2b敲除（Cyp2b-null）小鼠分别饲喂正常饮食（ND）或含0.1%甲硫氨酸、脂肪占比62%的胆碱缺乏L氨基酸限定高脂饮食（CDAHFD），持续8周。采集各处理组雌雄小鼠的肝脏组织并提取总RNA，开展RNA测序分析。测序结果显示，Cyp2b缺失对雌性小鼠具有保护作用，但对雄性小鼠则加重病理损伤。肝脏基因表达分析表明，在饲喂CDAHFD的野生型雌性小鼠及Cyp2b敲除雄性小鼠中，I-III相异生物质代谢相关基因与炎症应答相关基因的下调数量显著更多。本研究借助Illumina测序技术，通过比较饲喂CDAHFD 8周的野生型与Cyp2b敲除小鼠的肝脏转录组，从转录组层面探究Cyp2b在饮食诱导NASH中的作用。