HYPERTHYROIDISM IN BHE CDB RATS DOES NOT INDUCE AN INCREASE IN MITOCHONDRIAL RESPIRATION

The effects of thyroxine (T4) treatment and hydrogenated coconut oil (HCO) feeding on mitochondrial metabolism were studied in BHE/cdb rats. BHE/cdb rats were fed either a 6% com oil (CO) or HCO diet for 4 weeks and injected with 10 mug T4/day/100 g body weight during the last week. Hyperthyroidism was confirmed by measuring serum hormone levels and the activity of Ca++, Mg++ ATPase, and the a glycerophosphate shuttle. All were significantly elevated. Respiration supported by succinate, beta-hydroxybutyrate, pyruvate plus malate, alpha ketoglutarate, palmitoyl CoA, palmitoyl carnitine, octanoyl CoA, and octanoyl carnitine was determined. With the TCA cycle intermediates, T4 failed to induce an increase in state 3 respiration despite having an effect on shuttle and ATPase activity. There was no effect of diet or T4 on the transition temperatures or on the upper or lower activation energies of succinate-supported respiration. The lack of a T4 effect on respiration supported by the TCA cycle intermediates suggests a strain-specific aberration in the responsiveness of the mitochondrial respiratory chain to T4 induction. This suggests that this treatment might be a powerful tool to probe the role of mitochondrial dysfunction in the progressive development of the abnormal glucose tolerance in BHE/cdb rats as they age.