Defective regulation of thyroxine 5'-deiodinase in brown adipose tissue of ob/ob mice

Genetically obese (ob/ob) and lean (+/?) mice were exposed to a cold (14 degrees C) environment for 1, 3, 6, 12, 16, or 24 h or remained in a warm (28 degrees C) environment. In ob/ob mice the increase in brown adipose tissue (BAT) thermogenesis (mitochondrial GDP binding) was low and the increase in thyroxine 5'-deiodinase (T5'D) was delayed; there was a reduced increase in serum 3,5,3'-triiodothyronine (T3) level and these mice became hypothermic. Content of uncoupling protein (UCP) was low in BAT of obese mice and no cold-induced increase occurred. Adrenalectomy of obese mice before exposure to cold (14 degrees C) improved defective thermogenic response of BAT and thermoregulation, restored to normal the increases in T5'D activity and serum T3 level, and promoted an exaggerated increase in UCP content, detectable after only 6 h. Adrenalectomy of cold-exposed lean mice did not alter thermoregulation, the increase in BAT T5'D activity, or the increase in serum T3 but enhanced the thermogenic response and allowed a higher UCP content in BAT of cold-exposed mice. We conclude that suppression of the cold-induced increase in T5'D activity in BAT can be added to the other known corticosterone-dependent anomalies of the ob/ob mouse. We speculate that lack of the cold-induced increase in T5'D in BAT of the ob/ob mouse prevents the normal participation of T3 in the trophic response of BAT to cold and underlies the abnormality in this response.