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

Détails

ID Serval
serval:BIB_2BC682719869
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance.
Périodique
Hepatology
Auteur(s)
Lee H.Y., Birkenfeld A.L., Jornayvaz F.R., Jurczak M.J., Kanda S., Popov V., Frederick D.W., Zhang D., Guigni B., Bharadwaj K.G., Choi C.S., Goldberg I.J., Park J.H., Petersen K.F., Samuel V.T., Shulman G.I.
ISSN
1527-3350 (Electronic)
ISSN-L
0270-9139
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
54
Numéro
5
Pages
1650-1660
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
10/09/2015 13:28
Dernière modification de la notice
08/05/2019 16:22
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