Thyroid hormone has been known for decades as a hormone with profound effects on energy expenditure and ability to control weight. The regulation of energy expenditure by thyroid hormone primarily occurs via regulation of the activity, or expression, of uncoupling proteins in peripheral tissues. However, mechanistically this requires a signal from the brain to change circulating levels of thyroxine and thyroid hormone or increased sympathetic drive to peripheral tissues to alter local thyroid hormone levels via increased expression of type 2 deiodinase. However, little consideration has been given to the potential role and involvement of thyroid hormones action in the brain in the regulation of energy balance. Recent evidence implicates thyroid hormone as a shortterm signal of energy deficit imposed by starvation. Furthermore, thyroid hormone action within the hypothalamus is involved in adjusting long-term energy expenditure in seasonal animals which endure food shortages in winter. Evidence from several studies suggests that regulation of type 2 and type 3 deiodinase enzymes in tanycytes of the third ventricle are gatekeepers of thyroid hormone levels in the hypothalamus. This paper reviews some of the evidence for the role of deiodinase enzymes and the actions of thyroid hormone in the hypothalamus in the regulation of energy balance.
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