Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis.
Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis.
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DOI：
10.1038/srep21721
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发表时间：
2016-02-17
影响因子：
4.6
通讯作者：
Wada J
中科院分区：
文献类型：
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作者：
Nakatsuka A;Matsuyama M;Yamaguchi S;Katayama A;Eguchi J;Murakami K;Teshigawara S;Ogawa D;Wada N;Yasunaka T;Ikeda F;Takaki A;Watanabe E;Wada J
尽管肥胖无疑是非酒精性脂肪性肝炎（NASH）的主要风险，但已认识到体重指数正常的瘦NASH患者的存在。在这里，我们报告，磷脂酰乙醇胺N-甲基转移酶（PEMT）不足是一个风险瘦NASH。喂食高脂肪-高蔗糖（HFHS）饮食的Pemt −/−小鼠受到饮食诱导的肥胖和糖尿病的保护，而它们表现出明显的脂肪性肝炎并发生了多发性肝脏肿瘤。Pemt通过与网格蛋白重链和p53形成复合物对p53驱动的转录产生抑制作用，喂食HFHS饲料的Pemt −/−小鼠表现出显著的肝细胞凋亡。此外，F-box蛋白31和肝细胞核因子4 α的高甲基化和mRNA表达抑制导致细胞周期蛋白D1的显著激活。NASH患者肝组织中PEMT mRNA的表达显著低于单纯脂肪变性患者，我们推测瘦型NASH具有PEMT活性不足的独特临床实体。
Although obesity is undoubtedly major risk for non-alcoholic steatohepatitis (NASH), the presence of lean NASH patients with normal body mass index has been recognized. Here, we report that the insufficiency of phosphatidylethanolamine N-methyltransferase (PEMT) is a risk for the lean NASH. The Pemt−/− mice fed high fat-high sucrose (HFHS) diet were protected from diet-induced obesity and diabetes, while they demonstrated prominent steatohepatitis and developed multiple liver tumors. Pemt exerted inhibitory effects on p53-driven transcription by forming the complex with clathrin heavy chain and p53, and Pemt−/− mice fed HFHS diet demonstrated prominent apoptosis of hepatocytes. Furthermore, hypermethylation and suppressed mRNA expression of F-box protein 31 and hepatocyte nuclear factor 4α resulted in the prominent activation of cyclin D1. PEMT mRNA expression in liver tissues of NASH patients was significantly lower than those with simple steatosis and we postulated the distinct clinical entity of lean NASH with insufficiency of PEMT activities.