Effects of thyroxine on rat brown fat and muscle thermogenesis in the cold

We studied whether the activation of rat brown adipose tissue (BAT) by cold exposure or by the administration of beta-3-noradrenergic agonist CGP-1217 7 could be prevented by the inhibition of thyroxine (T4) to triiodothyronin e (T3) conversion. Hypothyroid rats were treated with replacement doses of T4, T3 plus iopanoic acid (IA) or T3. Groups of rats were placed at 4 degre es C for 24 h or kept at room temperature. Cold exposure induced a signific ant increase in guanosine diphosphate (GDP) binding to BAT mitochondrial pr oteins in T4-treated rats, an effect not abolished by IA. No significant ch anges were seen in T3-treated rats. In rats maintained at room temperature and injected with CGP-12177, T4 induced a significant rise in GDP binding w hich was not blocked by IA. T3 also induced a significant increase in bindi ng. The study of mitochondrial oxygen consumption in muscle from cold-expos ed rats showed a marked decrease in consumption in T3-treated rats as compa red to values in the warm. Normal oxygen consumption was restored with 2-fo ld doses of T3 replacement, whereas 5-fold doses increased consumption abov e normal. The data suggest that in states with low or absent T3, T4 can sti mulate heat production and preserve normothermia.