Thyroid hormone signaling in energy homeostasis and energy metabolism

Abstract

The thyroid hormone (TH) plays a significant role in diverse processes related to growth, development, differentiation, and metabolism. TH signaling modulates energy expenditure through both central and peripheral pathways. At the cellular level, the TH exerts its effects after concerted mechanisms facilitate binding to the TH receptor. In the hypothalamus, signals from a range of metabolic pathways, including appetite, temperature, afferent stimuli via the autonomic nervous system, availability of energy substrates, hormones, and other biologically active molecules, converge to maintain plasma TH at the appropriate level to preserve energy homeostasis. At the tissue level, TH actions on metabolism are controlled by transmembrane transporters, deiodinases, and TH receptors. In the modern environment, humans are susceptible to an energy surplus, which has resulted in an obesity epidemic and, thus, understanding the contribution of the TH to cellular and organism metabolism is increasingly relevant.

Keywords: basal metabolic rate; cellular metabolism; deiodinases; energy homeostasis; thyroid hormone.

Figure 1

The role of thyroid hormone in energy homeostasis. In response to environmental stimuli (such as feeding or temperature) orto hormonal stimuli (such as leptin), hypothalamic pathways modulate sympathetic outflow and TH secretion through the hypothalamic-pituitary-thyroid axis. TH and sympathetic output act in multiple organ systems to affect energy metabolism and thus regulate whole-body energy homeostasis. In particular, TH signaling and SNS stimulation promote adaptive thermogenesis in BAT, regulate cardiovascular functions including blood pressure and heart rate, modulate glucose homeostasis through actions in the pancreatic β cell, regulate systemic TH clearance and endogenous glucose production in the liver, and effect other tissues including WAT and skeletal muscle.TRH: thyrotropin-releasing hormone; TH: thyroid hormone; SNS: sympathetic nervous system; BAT: brown adipose tissue; WAT: white adipose tissue.