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Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance

Lee, Hui-Young
Birkenfeld, Andreas L
Jurczak, Michael J
Kanda, Shoichi
Popov, Violeta
Frederick, David W
Zhang, Dongyan
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Published in Hepatology. 2011, vol. 54, no. 5, p. 1650-60
Abstract 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.
Keywords Animal FeedAnimalsApolipoprotein B-100/metabolismApolipoprotein C-III/blood/geneticsBlood Glucose/metabolismCholesterolVLDL/metabolism/secretionDietary Fats/pharmacologyDiglycerides/metabolismFatty Liver/genetics/metabolismFemaleGenetic Predisposition to Disease/geneticsHyperinsulinism/metabolismInsulin Resistance/geneticsMaleMiceMiceMutant StrainsNon-alcoholic Fatty Liver DiseasePostprandial Period/physiologyProtein Kinase C/metabolismTriglycerides/pharmacokinetics/secretion
PMID: 21793029
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LEE, Hui-Young et al. Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance. In: Hepatology, 2011, vol. 54, n° 5, p. 1650-60. doi: 10.1002/hep.24571

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Deposited on : 2017-12-21

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