Hepatic triglyceride lipaseplays an essential role in changing the lipid metabolism in genotype 1b hepatitis C virus replicon cells and hepatitis C patients

Hepatic triglyceride lipaseplays an essential role in changing the lipid metabolism in genotype 1b hepatitis C virus replicon cells and hepatitis C patients
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肝甘油三酯脂肪酶在改变基因型1b丙型肝炎病毒复制子细胞和丙型肝炎患者的脂质代谢中发挥重要作用

DOI:
10.1111/hepr.12072
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发表时间:
2013
期刊:
影响因子:
4.2
通讯作者:
Saito S
Saito S
中科院分区:
医学2区
文献类型:
--
作者:
ShinoharaY;Imajo K;Yoned M;Tomeno W;Ogawa Y;Fujita K;Kirikoshi H;Takahashi J;Funakoshi K;Ikeda M;Kato N;Nakajima A;Saito S

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目的近年来,尽管有关丙型肝炎病毒(HCV)相关脂蛋白谱改变的机制的研究还很有限,但已有研究表明脂蛋白谱与HCV之间存在相关性。在这项研究中,我们调查了脂蛋白谱之间的关联,根据颗粒大小分类,和脂蛋白metabolis.MethodsWe使用四种细胞进行本实验;全长基因组HCV RNA复制子细胞(OR 6),亚基因组HCV RNA复制子细胞(sO),和OR 6c细胞和sOc细胞,这是用干扰素-α处理的相同细胞系。通过高效液相色谱法测定培养基脂蛋白亚类中的甘油三酯(TG)水平。在OR 6、OR 6c、sO和sOc细胞中测量与脂蛋白代谢相关的几种分子的mRNA表达水平。为了证实一些使用在体外系统获得的结果,肝活检标本从患者也examined.ResultsThe大的低密度脂蛋白(LDL)和中LDL在培养基中的TG含量增加,只有在OR 6细胞。肝甘油三酯脂酶(HTGL)mRNA在OR 6细胞中的表达水平低于OR 6c细胞(P< 0.01)。对患者肝脏中HTGL表达水平的检查显示,与慢性B型肝炎或非酒精性脂肪性肝炎肝脏相比,慢性丙型肝炎肝脏中HTGL表达降低(P< 0.01)。
AimRecently, several studies have shown the existence of associations between lipoprotein profiles and hepatitis C virus (HCV), although only a limited amount of information is available about the mechanisms underlying the changes in the lipoprotein profiles associated with HCV. In this study, we investigated the association between lipoprotein profile, classified according to the particle size, and lipoprotein metabolism.MethodsWe used four kinds of cells for this experiment; full‐length genome HCV RNA replicon cells (OR6), sub‐genomic HCV RNA replicon cells (sO), and OR6c cells and sOc cells, which were the same cell lines treated with interferon‐α. The triglyceride (TG) levels in the lipoprotein subclasses of the culture medium were measured by high‐performance liquid chromatography. The mRNA expression levels of several molecules associated with lipoprotein metabolism were measured in the OR6, OR6c, sO and sOc cells. To confirm some of the results obtained using thein vitrosystem, liver biopsy samples obtained from the patients were also examined.ResultsThe content of TG in the large low‐density lipoprotein (LDL) and medium LDL in the culture medium was increased only in the OR6 cells. The hepatic triglyceride lipase (HTGL) mRNA expression levels were lower in the OR6 cells than in the OR6c cells (P< 0.01). Examination of the HTGL expression levels in the patients' livers revealed a decrease in HTGL expression in the chronic hepatitis C liver as compared with that in the chronic hepatitis B or non‐alcoholic steatohepatitis liver (P< 0.01).ConclusionWe showed that HCV inhibits HTGL production in hepatocytes, inducing a change of the lipoprotein profile.