| Authors |
Castellani LW, Gargalovic P, Febbraio M, Charugundla S, Jien ML, Lusis AJ
|
| Submitted By |
Willa Hsueh on 2/11/2009 |
| Status |
Published |
| Journal |
Journal of lipid research |
| Year |
2004 |
| Date Published |
12/1/2004 |
| Volume : Pages |
45(12) : 2377 - 2387 |
| PubMed Reference |
|
| Abstract |
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.
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| Genes |
| Symbol | Description |
| Apoa2 | apolipoprotein A-II |
| Cd36 | CD36 antigen |
| Scarb1 | scavenger receptor class B, member 1 |
|