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Am J Physiol Endocrinol Metab 286: E168-E175, 2004. First published September 30, 2003; doi:10.1152/ajpendo.00232.2003
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Human skeletal muscle PPAR{alpha} expression correlates with fat metabolism gene expression but not BMI or insulin sensitivity

Junlong Zhang,1 D. I. W. Phillips,2 Chunli Wang,1 and Christopher D. Byrne1

1Endocrinology and Metabolism Unit, Fetal Origins of Adult Disease Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD; and 2Medical Research Council Environmental Epidemiology Unit, Southampton General Hospital, Southampton SO16 5YD, United Kingdom

Submitted 22 May 2003 ; accepted in final form 27 September 2003

Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) 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{alpha} and with important genes regulating lipid metabolism in humans in vivo, we undertook hyperinsulinemic-euglycemic clamps and measured PPAR{alpha} mRNA levels and mRNA levels of lipid regulating PPAR{alpha} 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{alpha} 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{alpha} expression and genes regulating lipid metabolism are tightly linked, but there was no association between both insulin sensitivity and BMI with PPAR{alpha} expression in skeletal muscle.

peroxisome proliferator-activated receptor-{alpha}; messenger ribonucleic acid; insulin resistance; quantitative competitive polymerase chain reaction; skeletal muscle; body mass index



Address for reprint requests and other correspondence: C. D. Byrne, Endocrinology & Metabolism Unit, FOAD, Univ. of Southampton, CF96, Level F, Central Block, Southampton General Hospital, Southampton SO16 6YD, UK (E-mail: cdtb{at}soton.ac.uk).




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