脂肪性肝炎
生物
脂肪肝
脂类学
调解人
脂质代谢
单核苷酸多态性
脂肪变性
细胞生物学
生物信息学
内分泌学
基因
内科学
疾病
遗传学
医学
基因型
作者
Dario F. De Jesus,Tomohiko Kimura,Manoj Gupta,Rohit Kulkarni
标识
DOI:10.1016/j.chembiol.2023.06.001
摘要
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. We recently discovered that neuronal regeneration-related protein (NREP/P311), an epigenetically regulated gene reprogrammed by parental metabolic syndrome, is downregulated in human NAFLD. To investigate the impact of NREP insufficiency, we used RNA-sequencing, lipidomics, and antibody microarrays on primary human hepatocytes. NREP knockdown induced transcriptomic remodeling that overlapped with key pathways impacted in human steatosis and steatohepatitis. Additionally, we observed enrichment of pathways involving phosphatidylinositol signaling and one-carbon metabolism. Lipidomics analyses also revealed an increase in cholesterol esters and triglycerides and decreased phosphatidylcholine levels in NREP-deficient hepatocytes. Signalomics identified calcium signaling as a potential mediator of NREP insufficiency’s effects. Our results, together with the encouraging observation that several single nucleotide polymorphisms (SNPs) spanning the NREP locus are associated with metabolic traits, provide a strong rationale for targeting hepatic NREP to improve NAFLD pathophysiology.
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