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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)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0270-9139
e-ISSN 1527-3350
Zeitschrift Hepatology
Quellenangaben Band: 54, Heft: 5, Seiten: 1650-1660 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken, NJ
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)