Demonstration of in vivo metabolic effects of 3,5-di-iodothyronine

The objective of the present study was to test in vivo the metabolic effects of 3,5-di-iodothyronine (3,5-T-2) in unanesthetized and unrestrained male Sprague-Dawley rats. Amino acid and lipid metabolisms were investigated by breath tests using as tracers the C-13-carboxyl-labeled molecules of leucine, alpha-ketoisocaproic acid (KIC) and octanoic acid, in four different groups of rats: hypothyroid animals (receiving propylthiouracil (PTU) and iopanoic acid), hypothyroid animals treated with either a daily i.p. injection of 3,5-T-2 (25 mu g/100 g body weight), or tri-iodothyronine (T-3) (1 mu g/100 g body weight), and control euthyroid animals receiving equivalent volumes of the vehicle solutions. Energy expenditure was measured by continuous monitoring of O-2 consumption and CO2 production in these different groups. Daily energy expenditure was decreased by 30% in PTU-treated rats. The chronic treatments with 3,5-T-2 and T-3 restored daily energy expenditure to the control level. (CO2)-C-13 recovered in breath following the i.v. injection of octanoic acid-[1-C-13] was decreased in hypothyroid animals compared with control animals (P<0.05) and restored to control values by T-3 and 3,5-T-2 treatments. The (CO2)-C-13 recovered in breath after i.v. injection of leucine-[1-C-13] was increased in PTU-treated compared with control animals (P<0.05). Chronic treatment with either 3,5-T-2 or T-3 restored 13CO(2) to control values. Excretion of (CO2)-C-13 recovered in breath following the i.v. injection of KIC-[1-C-13] was increased in PTU-treated compared with control animals. Chronic treatments with either 3,5-T-2 or Tg did not restore KIC decarboxylation. These results suggest that 3,5-T-2 exerts metabolic effects on energy expenditure, on both lipid beta-oxidation and leucine metabolism in hypothyroid rats. We conclude that 3,5-T-2 is a metabolically active iodothyronine.