Abnormal thyroid hormone deiodination in tissues of ob/ob and db/db obese mice

To explore the relationships between thyroid hormone economy and defective thermogenesis in two genetically obese mouse strains, ob/ob and db/db, we measured iodothyronine deiodination in tissue homogenates and the T4 and T3 content of selected tissues. In lean mice acclimated at room temperature, type II 5'-deiodination in brown adipose tissue (BAT) homogenates rose 14.5-fold between 30 and 180 min of cold exposure at 4 C. In ob/ob mice kept at room temperature, type II 5'-deiodination rates in BAT homogenates were 2.29 times those in lean controls, but acute exposure to 4 C for 3 h caused a much smaller rise in 5'-deiodination in the ob/ob mice than in lean controls. Administration of 1 microgram/g norepinephrine caused similar elevations in BAT 5'-deiodination in ob/ob and lean mice. db/db mice had a defect in cold-stimulated BAT 5'-deiodination similar to that in the ob/ob mice in two of three experiments. In the obese animals of both strains, but not the lean mice, the magnitude of the rise in BAT type II deiodination after cold exposure was much greater in December than in warm months. Cerebrocortical homogenates from ob/ob mice had about 33% higher type II 5'-deiodination rates than those from lean controls, but showed normal type III T3 5'-deiodination. ob/ob liver homogenates had about 33% lower type I 5'-deiodination rates than controls. db/db, but not ob/ob, mice had lower serum T4 concentrations than controls. Both ob/ob and db/db mice had lower hepatic T4 concentrations than lean controls. The ob/ob animals had no alteration in brain T4 concentrations. Neither ob/ob or db/db mice had altered serum T3 concentrations, ob/ob mice had subnormal hepatic, but not brain, mean T3 concentrations. db/db mice also had reduced mean heptic T3 concentration. These results suggest that the subnormal cold-induced rise in ob/ob and db/db BAT type II 5'-deiodination is unrelated to thyroid status, perhaps being partly caused by defective sympathetic stimulation. This impaired deiodination response might result in subnormal intracellular T3 in BAT, thereby contributing to impaired thermogenesis. In contrast, the elevated cerebrocortical and unstimulated BAT type II deiodination and the decreased hepatic type I deiodination in the ob/ob mice are probably due to intracellular thyroid hormone deficiency.