Steatosis does not impair liver regeneration after partial hepatectomy
Steatosis does not impair liver regeneration after partial hepatectomy
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DOI：
10.1038/labinvest.2012.142
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发表时间：
2013-01-01
影响因子：
5
通讯作者：
Canbay, Ali
中科院分区：
文献类型：
--
作者：
Sydor, Svenja;Gu, Yanli;Canbay, Ali
肝脏脂肪变性是非酒精性脂肪性肝病（NAFLD）的一个关键特征。单纯性脂肪变性中脂滴结合甘油三酯的储存是生理惰性的，而非酒精性脂肪性肝炎（NASH）与肝细胞损伤和细胞凋亡相关。游离脂肪酸（FFA）的线粒体氧化，来自脂滴和肝细胞的摄取，是一种快速和有效的能量供应的方式为增殖细胞和FFA酯化提供底物的脂质合成和细胞增殖。因此，我们研究了西方饮食（WD）诱导的单纯性脂肪变性是否能改善部分肝切除术（PHx）后的肝再生。在小鼠模型中，WD喂养6周引起单纯性脂肪变性，伴有肝脂滴和甘油三酯积聚，伴随着脂肪酸转运蛋白（FATP）、死亡受体（DR）、促凋亡基因和抗凋亡基因、肝细胞生长因子（Hgf）的诱导以及血清瘦素水平的升高。PHx后，WD喂养小鼠的肝细胞增殖较高，并与FATP和Hgf诱导相关。此外，在标准饮食（SD）小鼠中观察到的Erk 1/2（细胞外相关MAP激酶1/2）去磷酸化在WD动物中减少。尽管DR上调，但脂肪变性肝脏中的PHx不影响肝细胞凋亡。WD诱导的脂肪变性增强肝细胞增殖，这伴随着增加的Hgf和瘦素信号传导以及Erk 1/2磷酸化。因此，诱导轻度脂肪变性可能有利于肝切除术的手术结果。实验室调查（2013）93，20-30; doi：10.1038/labinvest.2012.142;在线发表2012年10月15日
Hepatic steatosis is a key feature of non-alcoholic fatty liver disease (NAFLD). While storage of lipid droplet-bound triglycerides in simple steatosis is physiologically inert, non-alcoholic steatohepatitis (NASH) is associated with hepatocyte damage and apoptosis. Mitochondrial oxidation of free fatty acids (FFA), derived from lipid droplets and hepatocellular uptake, is a rapid and effective way of energy supply for proliferating cells and FFA esterification provides substrates for lipid synthesis and cell proliferation. Thus, we investigated whether simple steatosis induced by western diet (WD) improves liver regeneration after partial hepatectomy (PHx). WD feeding for 6 weeks caused simple steatosis with hepatic lipid droplet and triglyceride accumulation accompanied by induction of fatty acid transport proteins (FATP), death receptors (DR), pro-and anti-apoptotic genes, hepatocyte growth factor (Hgf) as well as increased serum leptin levels in a mouse model. After PHx, liver cell proliferation was higher in WD-fed mice and associated with FATP and Hgf induction. In addition, Erk1/2 (extracellular-related MAP kinase 1/2) dephosphorylation observed in standard diet (SD) mice was reduced in WD animals. PHx in steatotic livers did not affect hepatocyte apoptosis, despite DR upregulation. WD-induced steatosis enhances liver cell proliferation, which is accompanied by increased Hgf and leptin signaling as well as Erk1/2 phosphorylation. Induction of mild steatosis may therefore be beneficial for surgical outcome of hepatectomies. Laboratory Investigation (2013) 93, 20-30; doi: 10.1038/labinvest.2012.142; published online 15 October 2012