Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance.
Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance.
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DOI：
10.1002/hep.24571
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发表时间：
2011-11
期刊：
影响因子：
13.5
通讯作者：
Shulman, Gerald I.
中科院分区：
文献类型：
--
作者：
Lee, Hui-Young;Birkenfeld, Andreas L.;Jornayvaz, Francois R.;Jurczak, Michael J.;Kanda, Shoichi;Popov, Violeta;Frederick, David W.;Zhang, Dongyan;Guigni, Blas;Bharadwaj, Kalyani G.;Choi, Cheol Soo;Goldberg, Ira J.;Park, Jae-Hak;Petersen, Kitt F.;Samuel, Varman T.;Shulman, Gerald I.
最近发现非酒精性脂肪性肝病（NAFLD）和胰岛素抵抗与携带APOC3基因胰岛素反应元件单核苷酸多态性的人血浆载脂蛋白CIII （APOC3）浓度升高有关。为了研究APOC3表达增加是否会使小鼠易患NAFLD和肝脏胰岛素抵抗，研究人员在常规食物或高脂肪饮食（HFD）后对人类APOC3过表达（ApoC3Tg）小鼠进行代谢表型分析。饲喂HFD后，ApoC3Tg小鼠肝脏甘油三酯积累增加，这与细胞膨胀和炎症变化有关。通过高胰岛素-正血糖钳夹评估，ApoC3Tg小鼠还表现出严重的肝脏胰岛素抵抗，这主要归因于肝脏二酰基甘油含量增加，蛋白激酶C-ε活化和胰岛素刺激Akt2活性降低。hfd喂养的ApoC3Tg小鼠肝脏甘油三酯含量增加可归因于肝脏甘油三酯摄取增加70%和肝脏甘油三酯分泌减少50%。结论：这些数据表明，血浆中APOC3浓度的增加使小鼠易发生饮食诱导的NAFLD和肝脏胰岛素抵抗。(肝脏病学54:1650 2011;1660)
Nonalcoholic fatty liver disease (NAFLD) and insulin resistance have recently been found to be associated with increased plasma concentrations of apolipoprotein CIII (APOC3) in humans carrying single nucleotide polymorphisms within the insulin response element of the APOC3 gene. To examine whether increased expression of APOC3 would predispose mice to NAFLD and hepatic insulin resistance, human APOC3 overexpressing (ApoC3Tg) mice were metabolically phenotyped following either a regular chow or high-fat diet (HFD). After HFD feeding, ApoC3Tg mice had increased hepatic triglyceride accumulation, which was associated with cellular ballooning and inflammatory changes. ApoC3Tg mice also manifested severe hepatic insulin resistance assessed by a hyperinsulinemic-euglycemic clamp, which could mostly be attributed to increased hepatic diacylglycerol content, protein kinase C-ε activation, and decreased insulin-stimulated Akt2 activity. Increased hepatic triglyceride content in the HFD-fed ApoC3Tg mice could be attributed to a ≍70% increase in hepatic triglyceride uptake and ≍50% reduction hepatic triglyceride secretion. Conclusion: These data demonstrate that increase plasma APOC3 concentrations predispose mice to diet-induced NAFLD and hepatic insulin resistance. (Hepatology 2011;54:1650-1660)
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影响因子：
9.8
作者：
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通讯作者：
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影响因子：
15.9
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在多种族样本中，APOC3基因的-455T> C启动子多态性与代谢综合征之间的关联。
影响因子：
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影响因子：
15.9
作者：
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通讯作者：
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