Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle

The mechanism underlying the regulation of basal metabolic rate by thyroid hormone remains unclear. Although it has been suggested that thyroid hormone might uncouple substrate oxidation from ATP synthesis, there are no data from studies on humans to support this hypothesis. To examine this possibility, we used a novel combined C-13/P-31 nuclear magnetic resonance (NMR) approach to assess mitochondrial energy coupling in skeletal muscle of seven healthy adults before and after three days of triiodothyronine (T-3) treatment. Rates of ATP synthesis and tricarboxylic acid (TCA) cycle fluxes were measured by P-31 and C-13 NMR spectroscopy, respectively, and mitochondrial energy coupling was assessed as the ratio. Muscle TCA cycle flux increased by approximately 70% following T-3 treatment. In contrast, the rate of ATP synthesis remained unchanged. Given the disproportionate increase in TCA cycle flux compared with ATP synthesis, these data suggest that T-3 promotes increased thermogenesis in part by promoting mitochondrial energy uncoupling in skeletal muscle.