The effect of thyroid hormones on metabolism has long supported their potential as drugs to stimulate fat loss, but the following induction of a thyrotoxic state has greatly limited their use. 3,5-diiodo-L-thyronine, also known as T2, is a naturally occurring iodothyronine deiodinase. Iodothyronine deiodinases are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Recent research suggests that T2 stimulates metabolic rate via mechanisms involving the mitochondrial apparatus.

When examined whether this effect would result in reduced energy storage. Here, we show that T2 administration to rats receiving a high-fat diet (HFD) reduces both obesity and body weight gain without inducing thyrotoxicity. Rats receiving HFD + T2 showed (when compared with rats receiving HFD alone) a 13% lower body weight, a 42% higher liver fatty acid oxidation rate, appoximately 50% less fat mass, a complete disappearance of fat from the liver and significant reductions in the serum triglyceride and cholesterol levels (-52% and -18%, respectively).

Thyroid hormones and thyroid-stimulating hormone (TSH) serum levels were not influenced by T2 administration. The biochemical mechanism underlying the effects of T2 on liver metabolism involves the carnitine palmitoyl-transferase system and mitochondrial uncoupling.

If the results hold true for humans, pharmacological administration of T2 might serve to counteract the problems associated with overweight, such as accumulation of lipids in liver and serum, without inducing thyrotoxicity. However, the results reported here do not exclude deleterious effects of T2 on a longer time scale as well as do not show that T2 acts in the same way in humans.

3,5-diiodo-L-thyronine (T2), increases the activity of the redox-sensitive protein deacetylase SIRT1, which has been associated with improvements in healthy ageing. Findings suggest that T3, T2, and their signaling pathways, such as those involving SIRT1 and AMP-activated protein kinase (AMPK), are associated with improvements in diet-induced obesity and insulin resistance emphasize the potential importance of the thyroid during ageing and in ageing-associated metabolic diseases.

Sources: National Center for Biotechnology Information, U.S. National Library of Medicine, Healthy Ageing: Focus on Iodothyronines