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1 Department of Kinesiology, University of Waterloo, Waterloo, Ontario N2L 3G1; 3 Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta T5G 2S2, Canada; 2 Department of Physiology, Maastricht University, 6200 MD Maastricht, The Netherlands; 4 Glaxo SmithKline, Miami, Florida 33134; and 5 Thrombosis and Vascular Biology Laboratory, Otsuka America Pharmaceutical, Rockville, Maryland 20850
We have examined the effects of streptozotocin (STZ)-induced diabetes (moderate and severe) on fatty acid transport and fatty acid transporter (FAT/CD36) and plasma membrane-bound fatty acid binding protein (FABPpm) expression, at the mRNA and protein level, as well as their plasmalemmal localization. These studies have shown that, with STZ-induced diabetes, 1) fatty acid transport across the plasma membrane is increased in heart, skeletal muscle, and adipose tissue and is reduced in liver; 2) changes in fatty acid transport are generally not associated with changes in fatty acid transporter mRNAs, except in the heart; 3) increases in fatty acid transport in heart and skeletal muscle occurred with concomitant increases in plasma membrane FAT/CD36, whereas in contrast, the increase and decrease in fatty acid transport in adipose tissue and liver, respectively, were accompanied by concomitant increments and reductions in plasma membrane FABPpm; and finally, 4) the increases in plasma membrane transporters (FAT/CD36 in heart and skeletal muscle; FABPpm in adipose tissue) were attributable to their increased expression, whereas in liver, the reduced plasma membrane FABPpm appeared to be due to its relocation within the cell in the face of slightly increased expression. Taken together, STZ-induced changes in fatty acid uptake demonstrate a complex and tissue-specific pattern, involving different fatty acid transporters in different tissues, in combination with different underlying mechanisms to alter their surface abundance.
fatty acid transporter CD6; plasma membrane-bound fatty acid binding protein; muscle; heart; liver; adipose tissue
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