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Journal of Lipid Research, Vol. 46, 1295-1302, June 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
* Departments of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
** Department of Biochemical Physiology and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
Published, JLR Papers in Press, March 16, 2005. DOI 10.1194/jlr.M400426-JLR200
1 To whom correspondence should be addressed. e-mail: s.coort{at}gen.unimaas.nl
Thiazolidinediones (TZDs) increase tissue insulin sensitivity in diabetes. Here, we hypothesize that, in adipose tissue, skeletal muscle, and heart, alterations in protein-mediated FA uptake are involved in the effect of TZDs. As a model, we used obese Zucker rats, orally treated for 16 days with 5 mg rosiglitazone (Rgz)/kg body mass/day. In adipose tissue from Rgz-treated rats, FA uptake capacity increased by 2.0-fold, coinciding with increased total contents of fatty acid translocase (FAT/CD36; 2.3-fold) and fatty acid transport protein 1 (1.7-fold) but not of plasmalemmal fatty acid binding protein, whereas only the plasmalemmal content of FAT/CD36 was changed (increase of 1.7-fold). The increase in FA uptake capacity of adipose tissue was associated with a decline in plasma FA and triacylglycerols (TAGs), suggesting that Rgz treatment enhanced plasma FA extraction by adipocytes. In obese hearts, Rgz treatment had no effect on the FA transport system, yet the total TAG content decreased, suggesting enhanced insulin sensitivity. Also, in skeletal muscle, the FA transport system was not changed. However, the TAG content remained unaltered in skeletal muscle, which coincided with increased cytoplasmic adipose-type FABP content, suggesting that increased extramyocellular TAGs mask the decline of intracellular TAG in muscle.
In conclusion, our study implicates FAT/CD36 in the mechanism by which Rgz increases tissue insulin sensitivity.
Abbreviations: A-FABPc, adipose-type cytoplasmic fatty acid binding protein; FABPpm, plasmalemmal fatty acid binding protein; FAT/CD36, fatty acid translocase; FATP, fatty acid transport protein; PPAR
, peroxisome proliferator-activated receptor ; PPRE, peroxisome proliferator response element; Rgz, rosiglitazone; TAG, triacylglycerol; TZD, thiazolidinedione
Supplementary key words rosiglitazone • peroxisome proliferator-activated receptor • insulin resistance • long-chain fatty acids • fatty acid translocase • fatty acid transport protein 1 • plasmalemmal fatty acid binding protein • fatty acid uptake capacity
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