The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes
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abstract
BACKGROUND: Long-chain fatty acids (LCFAs) cross the plasma membrane via a protein-mediated mechanism involving one or more LCFA-binding proteins. Among these, FAT/CD36 has been identified as key LCFA transporter in the heart and skeletal muscle, where it is regulated acutely and chronically by insulin. In skeletal muscle, FAT/CD36 expression and/or subcellular distribution is altered in obesity and type 2 diabetes. There is limited information as to whether the expression of this protein is also altered in subcutaneous and/or visceral adipose tissue depots in human obesity or type 2 diabetes. OBJECTIVES: To compare (a) the expression of FAT/CD36 in subcutaneous and visceral adipose tissue depots in lean, overweight, and obese individuals and in type 2 diabetics, (b) to determine whether the protein expression of FAT/CD36 in these depots is associated with the severity of insulin resistance (type 2 diabetes>obese>overweight/lean) and (c) whether FAT/CD36 protein expression in these adipose tissue depots is associated with alterations in circulating substrates and hormones. SUBJECTS: Subjects who were undergoing abdominal surgery and who were lean (n=10; three men, seven women), overweight (n=10; three men, seven women) or obese (n=7; one man, six women), or who had been diagnosed with type 2 diabetes (n=5; one man, four women) participated in this study. MEASUREMENTS: Subcutaneous and visceral adipose tissue samples, as well as blood samples, were obtained from the subjects while under general anesthesia. Adipose tissue samples were analyzed for FAT/CD36 using Western blotting. Serum samples were analyzed for glucose, insulin, FFA and leptin. BMI was also calculated. RESULTS: Subcutaneous adipose tissue FAT/CD36 expression was upregulated by +58, +76 and +150% in overweight, obese and type 2 diabetics, respectively. Relative to subcutaneous adipose tissue, visceral adipose tissue FAT/CD36 expression was upregulated in lean (+52%) and overweight subjects (+30%). In contrast, in obese subjects and type 2 diabetics, no difference in FAT/CD36 protein expression was observed between their subcutaneous and visceral adipose tissue depots (P>0.05). The subcutaneous adipose tissue FAT/CD36 expression (R=0.85) and the visceral adipose tissue FAT/CD36 expression (R=0.77) were associated with alteration in BMI and circulating glucose and insulin. CONCLUSIONS: Subcutaneous adipose tissue FAT/CD36 expression is upregulated in obesity and type 2 diabetes. As FAT/CD36 expression is not different in lean, overweight and obese subjects, and was only increased in type 2 diabetics, it appears that visceral adipose tissue FAT/CD36 may respond in a less dynamic manner to metabolic disturbances than subcutaneous adipose tissue FAT/CD36.
