Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance.
Details
Serval ID
serval:BIB_2BC682719869
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance.
Journal
Hepatology
ISSN
1527-3350 (Electronic)
ISSN-L
0270-9139
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
54
Number
5
Pages
1650-1660
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
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.
CONCLUSION: These data demonstrate that increase plasma APOC3 concentrations predispose mice to diet-induced NAFLD and hepatic insulin resistance.
CONCLUSION: These data demonstrate that increase plasma APOC3 concentrations predispose mice to diet-induced NAFLD and hepatic insulin resistance.
Keywords
Animal Feed, Animals, Apolipoprotein B-100/metabolism, Apolipoprotein C-III/blood, Apolipoprotein C-III/genetics, Blood Glucose/metabolism, Cholesterol, VLDL/metabolism, Cholesterol, VLDL/secretion, Dietary Fats/pharmacology, Diglycerides/metabolism, Fatty Liver/genetics, Fatty Liver/metabolism, Female, Genetic Predisposition to Disease/genetics, Hyperinsulinism/metabolism, Insulin Resistance/genetics, Male, Mice, Mice, Mutant Strains, Non-alcoholic Fatty Liver Disease, Postprandial Period/physiology, Protein Kinase C/metabolism, Triglycerides/pharmacokinetics, Triglycerides/secretion
Pubmed
Web of science
Open Access
Yes
Create date
10/09/2015 12:28
Last modification date
20/08/2019 13:11