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

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-r...

Full description

Saved in:
Bibliographic Details
Published in:Journal of lipid research 2004-12, Vol.45 (12), p.2377-2387
Main Authors: Castellani, Lawrence W., Gargalovic, Peter, Febbraio, Maria, Charugundla, Sarada, Jien, Ming-Len, Lusis, Aldons J.
Format: Article
Language:English
Subjects:
Animals
Apolipoprotein A-II - biosynthesis
Apolipoprotein A-II - genetics
CD36/fat
fatty acid oxidation
fatty acids
Female
Gene Dosage
Glycogen - metabolism
Heterozygote
high density lipoproteins
Homozygote
Insulin Resistance - genetics
Insulin Resistance - physiology
Liver - metabolism
Male
Mice
Mice, Transgenic
Muscle, Skeletal - metabolism
triglycerides
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M400345-JLR200