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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/R1202    most recent 90820.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bonen, A. Articles by Luiken, J. J. F. P. PubMed PubMed Citation Articles by Bonen, A. Articles by Luiken, J. J. F. P.

Articles

Cardiac and skeletal muscle fatty acid transport and transporters and triacylglycerol and fatty acid oxidation in lean and Zucker diabetic fatty rats

¹Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; ²Thrombosis Research Laboratory, Otsuka Maryland Medicinal Laboratories, Rockville, Maryland; and ³Department of Molecular Genetics, Maastricht University, Maastricht, The Netherlands

Submitted October 9, 2008 ; accepted in final form July 23, 2009

We examined fatty acid transporters, transport, and metabolism in hearts and red and white muscles of lean and insulin-resistant (week 6) and type 2 diabetic (week 24) Zucker diabetic fatty (ZDF) rats. Cardiac fatty acid transport was similar in lean and ZDF hearts at week 6 but was reduced at week 24 (–40%) in lean but not ZDF hearts. Red muscle of ZDF rats exhibited an early susceptibility to upregulation (+66%) of fatty acid transport at week 6 that was increased by 50% in lean and ZDF rats at week 24 but remained 44% greater in red muscle of ZDF rats. In white muscle, no differences were observed in fatty acid transport between groups or from week 6 to week 24. In all tissues (heart and red and white muscle), FAT/CD36 protein and plasmalemmal content paralleled the changes in fatty acid transport. Triacylglycerol content in red and white muscles, but not heart, in lean and ZDF rats correlated with fatty acid transport (r = 0.91) and sarcolemmal FAT/CD36 (r = 0.98). Red and white muscle fatty acid oxidation by isolated mitochondria was not impaired in ZDF rats but was reduced by 18–24% in red muscle of lean rats at week 24. Thus, in red, but not white, muscle of insulin-resistant and type 2 diabetic animals, a marked upregulation in fatty acid transport and intramuscular triacylglycerol was associated with increased levels of FAT/CD36 expression and plasmalemmal content. In heart, greater rates of fatty acid transport and FAT/CD36 in ZDF rats (week 24) were attributable to the inhibition of age-related reductions in these parameters. However, intramuscular triacylglycerol did not accumulate in hearts of ZDF rats. Thus insulin resistance and type 2 diabetes are accompanied by tissue-specific differences in FAT/CD36 and fatty acid transport and metabolism. Upregulation of fatty acid transport increased red muscle, but not cardiac, triacylglycerol accumulation. White muscle lipid metabolism dysregulation was not observed.

plasma membrane-associated fatty acid-binding protein; FAT/CD36; GLUT4; mitochondria; giant vesicles