Hypothalamic effects of thyroid hormone

Thyroid hormone (TH) is a key driver of metabolism in mammals. Plasma concentrations of TH are kept within a narrow range by negative feedback regulation in the hypothalamus-pituitary-thyroid (HPT) axis. Plasma TH concentrations are an important determinant of metabolic processes in liver and brown adipose tissue (BAT). In addition to endocrine effects of TH derived from the circulation, recent studies have demonstrated additional neural routes for intrahypothalamic thyroid hormone to regulate metabolism in liver and BAT via the sympathetic and parasympathetic branch of the autonomic nervous system (ANS). This review provides an overview of studies reporting metabolic effects of selective administration of T3 within hypothalamic nuclei including the paraventricular nucleus (PVN), the ventromedial nucleus (VMH), the arcuate nucleus (Arc), and the anterior hypothalamic area (AHA). This overview of the literature suggests that intrahypothalamic T3 can have profound effects on hepatic glucose production and insulin sensitivity, energy expenditure in BAT, cardiovascular function and feeding behavior. As the experiments have been performed in experimental animals exclusively, and the timing and route of T3 administration may be an important determinant of effect size, the clinical relevance of these metabolic effects in the chronic setting remains to be established.