Thyroid hormone and other regulators of uncoupling proteins.

The role of the thyroid gland in the regulation of metabolic rate has been known since the last century. The knowledge that thyroid hormones increase energy expenditure, in part by lowering metabolic efficiency, dates from the 1950s. Presumably thyroid hormones regulate energy expenditure and efficiency by controlling the rate of transcription of specific genes. However, the number, identity, and relative contributions of these genes are not known. The uncoupling proteins (UCPs) are obvious candidates to mediate thyroid thermogenesis. UCP1 is not a major contributor, since thyrotoxicosis decreases UCP1 expression and inactivates brown fat. Discovery of UCP3 and its regulation by T3 in muscle is an exciting observation, consistent with a role for UCP3 in thyroid thermogenesis. Since free fatty acids appear to regulate UCP3 expression and T3 stimulates lipolysis, further experiments are required to determine if T3 regulation of UCP3 expression is direct or not.