The Thyroid Hormone Axis: Its Roles in Body Weight Regulation, Obesity, and Weight Loss

Abstract

In humans and other vertebrates, thyroid hormone is essential to the development and function of every tissue in the body. During adulthood, thyroid hormone is critical to mediating changes in metabolism as it is key to the regulation of resting energy expenditure, body temperature, and hepatic lipid metabolism, to name a few. The hypothalamic-pituitary-thyroid (HPT) axis functions as a negative feedback loop where thyrotropin-releasing hormone (TRH) is released from neurons in the paraventricular nucleus of the hypothalamus and stimulates the secretion of thyroid-stimulating hormone (TSH) from the pituitary. TSH signals the release of thyroid hormones, both the prohormone thyroxine (T4) and the active hormone triiodothyronine (T3) from the thyroid. Through central actions, TRH and TSH are negatively regulated by T3 at several levels including gene transcription and prohormone processing. The HPT axis is a dynamic system that responds to environment including food availability, environmental temperature, weight loss, and illness normally through central mechanisms. The following chapter will focus on the regulation of thyroid hormone, its role in body weight, and how weight loss can affect thyroid hormone levels. Currently, thyroid hormone is a poor therapeutic to treat obesity and to elevate energy expenditure because it has detrimental effects such as atrial fibrillation, osteoporosis, and muscle wasting. Researchers are focusing on thyroid hormone analogs as therapeutics for weight loss to eliminate the negative side effects. As detailed below, thyroid hormone action in peripheral tissues can be just as important to energy expenditure as the central regulation of thyroid hormone.