Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers.
Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers.
复制标题
在人和大鼠非酒精脂肪肝肝中载脂蛋白A5表达增加。
DOI：
10.1097/pat.0000000000000251
复制
发表时间：
2015-06
期刊：
影响因子：
4.5
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Feng Q;Baker SS;Liu W;Arbizu RA;Aljomah G;Khatib M;Nugent CA;Baker RD;Forte TM;Hu Y;Zhu L
载脂蛋白 A5 (apoA5) 是甘油三酯 (TG) 代谢的有效调节因子，因此可能导致非酒精性脂肪肝 (NAFLD) 的发病机制，这种疾病的特征是肝细胞中富含过多的 TG 脂滴。为了检验这一假设，我们检查了儿童 NAFLD 肝脏中 apoA5 的 mRNA 表达，并与健康对照进行比较。根据微阵列和定量实时 PCR，与健康对照相比，人类 NAFLD 肝脏表现出升高的 apoA5 表达。 apoA5 表达水平与肝脏 TG 储存和脂滴标记物 (perilipin) 呈正相关，但与血浆 TG 水平不相关。这些观察结果在 NAFLD 大鼠模型中得到了证实。有趣的是，在培养的充满脂肪的 HepG2 细胞中，apoA5 表达没有改变，这表明脂肪储存不会在 NAFLD 肝脏中诱导 apoA5。因此，apoA5 与细胞内脂肪储存之间的相关性很可能是通过 apoA5 在促进细胞内脂肪储存方面的有效作用来解释的。我们的 NAFLD 患者和大鼠的胰岛素抵抗升高，这可能与 NAFLD 肝脏中 apoA5 表达升高有关。我们的数据支持这样的假设：apoA5 促进肝脏 TG 储存，因此有助于 NAFLD 的发病机制，并且可能代表治疗干预的潜在目标。
Apolipoprotein A5 (apoA5) is a potent regulator of triglyceride (TG) metabolism and therefore may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a disease characterised by excessive TG-rich lipid droplets in hepatocytes. To test this hypothesis, we examined the mRNA expression of apoA5 in paediatric NAFLD livers in comparison to healthy controls. According to microarray and quantitative real-time PCR, human NAFLD livers exhibited elevated apoA5 expression compared to healthy controls. The apoA5 expression levels were positively correlated with hepatic TG storage and a marker for lipid droplets (perilipin), but were not correlated with plasma TG levels. These observations were confirmed with a NAFLD rat model. Interestingly, apoA5 expression was not altered in cultured fat-laden HepG2 cells, demonstrating that fat storage does not induce apoA5 in NAFLD livers. Therefore, the correlation between apoA5 and intracellular fat storage is likely explained by the potent effect of apoA5 in promoting intracellular fat storage. Our NAFLD patients and rats had elevated insulin resistance, which may have a role in elevating apoA5 expression in NAFLD livers. Our data support the hypothesis that apoA5 promotes hepatic TG storage and therefore contributes to the pathogenesis of NAFLD, and may represent a potential target for therapeutic intervention.