PGC-1α's relationship with skeletal muscle palmitate oxidation is not present with obesity despite maintained PGC-1α and PGC-1β protein

Reduced skeletal muscle mitochondrial content and fatty acid oxidation are associated with obesity and insulin resistance. Although the exact mechanisms remain elusive, this may result from impaired mitochondrial biogenesis or reductions in the mitochondrial reticulum network. Therefore, the purpose of this study was to determine whether the protein contents of various transcription factors, including PGC-1 alpha and PGC-1 alpha and proteins associated with mitochondrial fusion events, were reduced in skeletal muscle of nine obese (BMI = 37.6 +/- 2.2 kg/m(-2)) compared with nine age-matched lean (BMI = 23.3 +/- 0.7 kg/m(-2)) women. The protein contents of PGC-1 alpha, PGC-1 beta, PPAR alpha, and tFAM were not reduced with obesity. In contrast, PPAR gamma was increased (+22%, P < 0.05) with obesity, and there was a trend toward an increase (+31%, P = 0.13) in PPAR delta/beta. In lean individuals, PGC-1 beta protein correlated with citrate synthase (CS; r = 0.67) and rates of palmitate oxidation (r = 0.87), whereas PGC-1 beta correlated with PPAR gamma (r = 0.90), PPAR delta/beta (r = 0.63), and cytochrome c oxidase IV (COX-IV; r = 0.63). In obese individuals, the relationship between PGC-1 alpha and CS was maintained (r = 0.65); however, the associations between PGC-1 alpha and palmitate oxidation (r = -0.38) and PGC-1 beta with PPAR gamma (r = 0.14), PPAR delta/beta (r = 0.21), and COX-IV (r = 0.01) were lost. In addition, mitofusin-1 (MFN-1), MFN-2, and dynamin-related protein-1 (DRP-1) total protein contents were not altered with obesity (P > 0.05). These data suggest that altered regulation, and not reductions in the protein contents of transcription factors, is associated with insulin resistance. Also, it does not appear that alterations in the proteins associated with mitochondrial network formation and degradation can account for the observed decrease in mitochondrial content.