3,5-Diiodo- l -thyronine and 3,5,3′-triiodo- l -thyronine both improve the cold tolerance of hypothyroid rats, but possibly via different mechanisms

Abstract

The effects of 3,5-diiodo-L-thyronine (3,5-T2, 2.5-10 microg/100 g BW) on cold tolerance, energy expenditure and oxidative capacity of four metabolically very active tissues (brown adipose tissue, skeletal muscle, liver and heart) were determined in hypothyroid, cold-exposed rats. Hypothyroid rats survived cold for only 3-4 days. 3,5-T2 improved survival dose dependently; with 10 microg/100 g BW the rats survived 3 weeks (limit of observation). This effect was paralleled by an increased energy expenditure of the whole animal for the entire 3 weeks. Similar effects were observed in hypothyroid rats treated with 3,3',5-triiodo-L-thyronine (T3). 3,5-T2 stimulated the specific oxidative capacity (expressed as cytochrome oxidase activity per milligram protein) of all four tissues dose dependently. When the oxidative capacity was expressed as total activity (cytochrome oxidase activity times organ weight), the percentage increases were of the same order. T3 exerted similar effects, but the changes in total activity were much greater than in specific activity, indicating an effect on the tissue trophism. The effect of 3,5-T2 on cold tolerance thus mimics the effect of T3, but via different cellular mechanisms. T3 seems to act primarily on the trophism of the tissues, while 3,5-T2 may act directly on mitochondria without an effect on tissue trophism.

Differential Effects of 3,5-Diiodo-L-Thyronine and 3,5,3’-Triiodo-L-Thyronine On Mitochondrial Respiratory Pathways in Liver from Hypothyroid Rats

“…When administered to hypothyroid rats, 3,5-T2 increases the animals' metabolic rate [13,14], cold tolerance [15], and their ability to use lipids as metabolic substrates [16][17][18][19][20]. In addition, when chronically administered to high fat diet fed rodents, 3,5-T2 contrasts fat accumulation and various dysmetabolic diseases associated with ectopic fat accumulation in lean tissues, such as liver steatosis and insulin resistance [21][22][23][24].…”

3,5-Diiodo-l-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement

“…In this context, we have shown that T 2 is able to 1) rapidly increase the resting metabolic rate of hypothyroid rats (24,29,30), 2) powerfully reduce adiposity in rats fed a high-fat diet by increasing the burning of fats (23), and 3) improve the survival of hypothyroid rats in the cold (25). Importantly, T 2 administration does not induce hypertrophy or hyperplasia of metabolically very active tissues (29,25) and does not induce thyrotoxicosis or cardiac acceleration in rodents or in humans (23). Moreover, within 1 h after its injection into hypothyroid rats, T 2 induces a rapid increase in mitochondrial oxidative capacity in skeletal muscle without involving transcription or translation mechanisms (27).…”

Thyroxine and tri-iodothyronine differently affect uncoupling protein-1 content and antioxidant enzyme activities in rat interscapular brown adipose tissue

“…Since di-iodothyronines, or at least 3,5-T 2 , are considered as active iodothyronines and not as simple products of T 4 or T 3 metabolism (Goglia et al 1999), it is likely that they can directly affect mitochondrial metabolism in IBAT. Di-iodothyronines can enhance the resting metabolic rate independently of protein synthesis (Moreno et al 1997) and improve the cold tolerance of hypothyroid rats (Lanni et al 1998).…”