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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.*

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

Hepatology 54, 1650-1660 (2011)
DOI Order publishers version
Open Access Green as soon as Postprint is submitted to ZB.
UNLABELLED: 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.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0270-9139
e-ISSN 1527-3350
Journal Hepatology
Quellenangaben Volume: 54, Issue: 5, Pages: 1650-1660 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)