Human skeletal muscle PPAR expression correlates with fat metabolism gene expression but not BMI or insulin sensitivity

Zhang, Junlong, D. I. W. Phillips, Chunli Wang, and Christopher D. Byrne. Human skeletal muscle PPAR expression correlates with fat metabolism gene expression but not BMI or insulin sensitivity. Am J Physiol Endocrinol Metab 286: E168–E175, 2004. First published September 30, 2003; 10.1152/ajpendo.00232.2003.—Peroxisome proliferator-activated receptor(PPAR ) is a key regulator of fatty acid oxidation in skeletal muscle, but few data exist from humans in vivo. To investigate whether insulin sensitivity in skeletal muscle and body mass index (BMI) were associated with skeletal muscle expression of PPAR and with important genes regulating lipid metabolism in humans in vivo, we undertook hyperinsulinemiceuglycemic clamps and measured PPAR mRNA levels and mRNA levels of lipid regulating PPAR response genes in skeletal muscle biopsies. mRNA levels were measured in 16 men, using a novel highly sensitive and specific medium throughput quantitative competitive PCR that allows reproducible measurement of multiple candidate mRNAs simultaneously. mRNA levels of PPAR were positively correlated with mRNA levels of CD36 (r 0.77, P 0.001), lipoprotein lipase (r 0.54, P 0.024), muscle-type carnitine palmitoyltransferase-I (r 0.54, P 0.024), uncoupling protein-2 (r 0.63, P 0.008), and uncoupling protein-3 (r 0.53, P 0.026), but not with measures of insulin sensitivity, BMI, or GLUT4, which plays an important role in insulin-mediated glucose uptake. Thus our data suggest that in humans skeletal muscle PPAR expression and genes regulating lipid metabolism are tightly linked, but there was no association between both insulin sensitivity and BMI with PPAR expression in skeletal muscle.