Mechanisms mediating insulin resistance in transgenic mice overexpressing mouse apolipoprotein A-II

Lawrence W. Castellani; Peter Gargalovic; Maria Febbraio; Sarada Charugundla; Ming-Len Jien; Aldons J. Lusis

Journal of Lipid Research (Dec 2004)

Mechanisms mediating insulin resistance in transgenic mice overexpressing mouse apolipoprotein A-II

Lawrence W. Castellani,
Peter Gargalovic,
Maria Febbraio,
Sarada Charugundla,
Ming-Len Jien,
Aldons J. Lusis

Affiliations

Lawrence W. Castellani: Department of Medicine/Cardiology, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Microbiology, Immunology, and Molecular Genetics, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Molecular Biology Institute, 47-123 CHS, University of California, Los Angeles, CA 90095; Division of Hematology/Oncology, Cornell University, New York, NY
Peter Gargalovic: Department of Medicine/Cardiology, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Microbiology, Immunology, and Molecular Genetics, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Molecular Biology Institute, 47-123 CHS, University of California, Los Angeles, CA 90095; Division of Hematology/Oncology, Cornell University, New York, NY
Maria Febbraio: Department of Medicine/Cardiology, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Microbiology, Immunology, and Molecular Genetics, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Molecular Biology Institute, 47-123 CHS, University of California, Los Angeles, CA 90095; Division of Hematology/Oncology, Cornell University, New York, NY
Sarada Charugundla: Department of Medicine/Cardiology, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Microbiology, Immunology, and Molecular Genetics, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Molecular Biology Institute, 47-123 CHS, University of California, Los Angeles, CA 90095; Division of Hematology/Oncology, Cornell University, New York, NY
Ming-Len Jien: Department of Medicine/Cardiology, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Microbiology, Immunology, and Molecular Genetics, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Molecular Biology Institute, 47-123 CHS, University of California, Los Angeles, CA 90095; Division of Hematology/Oncology, Cornell University, New York, NY
Aldons J. Lusis: Department of Medicine/Cardiology, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Microbiology, Immunology, and Molecular Genetics, 47-123 CHS, University of California, Los Angeles, CA 90095; Department of Molecular Biology Institute, 47-123 CHS, University of California, Los Angeles, CA 90095; Division of Hematology/Oncology, Cornell University, New York, NY

Journal volume & issue: Vol. 45, no. 12
pp. 2377 – 2387

Abstract

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We previously demonstrated that transgenic mice overexpressing mouse apolipoprotein A-II (apoA-II) exhibit several traits associated with the insulin resistance (IR) syndrome, including increased atherosclerosis, hypertriglyceridemia, obesity, and IR. The skeletal muscle appeared to be the insulin-resistant tissue in the apoA-II transgenic mice. We now demonstrate a decrease in FA oxidation in skeletal muscle of apoA-II transgenic mice, consistent with reports that decreased skeletal muscle FA oxidation is associated with increased skeletal muscle triglyceride accumulation, skeletal muscle IR, and obesity. The decrease in FA oxidation is not due to decreased carnitine palmitoyltransferase 1 activity, because oxidation of palmitate and octanoate were similarly decreased. Quantitative RT-PCR analysis of gene expression demonstrated that the decrease in FA oxidation may be explained by a decrease in medium chain acyl-CoA dehydrogenase. We previously demonstrated that HDLs from apoA-II transgenic mice exhibit reduced binding to CD36, a scavenger receptor involved in FA metabolism. However, studies of combined apoA-II transgenic and CD36 knockout mice suggest that the major effects of apoA-II are independent of CD36.Rosiglitazone treatment significantly ameliorated IR in the apoA-II transgenic mice, suggesting that the underlying mechanisms of IR in this animal model may share common features with certain types of human IR.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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