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 th e 1950s. Presumably thyroid hormones regulate energy expenditure and effici ency by controlling the rate of transcription of specific genes. However, t he number, identity, and relative contributions of these genes are not know n. The uncoupling proteins (UCPs) are obvious candidates to mediate thyroid thermogenesis. UCP1 is not a major contributor, since thyrotoxicosis decre ases UCP1 expression and inactivates brown fat. Discovery of UCP3 and its r egulation by T3 in muscle is an exciting observation, consistent with a rol e for UCP3 in thyroid thermogenesis. Since free fatty acids appear to regul ate UCP3 expression and T3 stimulates lipolysis, further experiments are re quired to determine if T3 regulation of UCP3 expression is direct or not.