INCREASED OXIDATIVE AND DELAYED GLYCOGENOLYTIC ATP SYNTHESIS IN EXERCISING SKELETAL-MUSCLE OF OBESE (INSULIN-RESISTANT) ZUCKER RATS

1. To examine metabolic correlates of insulin resistance in skeletal m uscle, we used P-31 magnetic resonance spectroscopy to study glycogeno lytic and oxidative ATP synthesis in leg muscle of lean and obese Zuck er rats in vivo during 6 min sciatic nerve stimulation at 2 Hz, 2. The water content of resting muscle was reduced by 21+/-7% in obese (insu lin-resistant) animals compared with lean animals, whereas the lipid c ontent was increased by 140+/-70%, These results suggest that intracel lular water content was reduced by 17% in obese animals, 3. During exe rcise, although twitch tensions were not significantly different in th e two groups, rates of total ATP synthesis (expressed per litre of int racellular water) were 48+/-20% higher in obese animals, suggesting a 50+/-8% reduction in intrinsic 'metabolic efficiency', Changes in phos phocreatine and ADP concentration were significantly greater in obese animals than in lean animals, whereas changes in intracellular pH did not differ, 4. These results imply that oxidative ATP synthesis during exercise is activated earlier in obese animals than in lean animals, This difference was not fully accounted for by the greater increase in the concentration of the mitochondrial activating signal ADP, Neither the post-exercise recovery kinetics of phosphocreatine nor the muscle content of the mitochondrial marker enzyme citrate synthase was signi ficantly different in the two groups, The increased oxidative ATP synt hesis in exercise must therefore be due to altered kinetics of mitocho ndrial activation by signals other than ADP, 5. Thus, the insulin-resi stant muscle of obese animals may compensate for its decreased efficie ncy (and consequent increased need for ATP) by increased reliance on o xidative ATP synthesis.