Control of energy metabolism by iodothyronines

One of the most widely recognized effects of thyroid hormones (TH) in adult mammals is their influence over energy metabolism. In the past, this has received much attention but, possibly because of the complex mode of action of thyroid hormones, no universally accepted mechanism to explain this effect has been put forward so far. Significant advances in our understanding of the biochemical processes involved in the actions of TH have been made in the last three decades and now it seems clear that TH can act through both nuclear-mediated and extranuclear-mediated pathways. TH increase energy expenditure, partly by reducing metabolic efficiency, with control of specific genes at the transcriptional level, being is thought to be the major molecular mechanism. However, both the number and the identity of the thyroid-hormone-controlled genes remain unknown, as do their relative contributions. The recent discovery of uncoupling proteins (UCPs) (in addition to UCP1 in brown adipose tissue) in almost all tissues in animals, including humans, has opened new perspectives on the understanding of the mechanisms involved in the regulation of energy metabolism by thyroid hormones. Other approaches have included the various attempts made to attribute changes in respiratory activity to a direct influence of thyroid hormones over the mitochondrial energy-transduction apparatus. In addition, an increasing number of studies has revealed that TH active in the regulation of energy metabolism include not only T3, but also other iodothyronines present in the biological fluids, such as 3,5-diiodothyronine (3,5-T2). This, in turn, may make it possible to explain some of the effects exerted by TH on energy metabolism that cannot easily be attributed to T3.