Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight

Summary

The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TRs), which function as ligand-inducible transcription factors. The TR-beta isoform (TRβ) is expressed in the ventromedial hypothalamus (VMH), a brain area important for control of energy homeostasis. Here, we report that selective knockdown of TRβ in the VMH of adult mice results in severe obesity due to hyperphagia and reduced energy expenditure. The observed increase in body weight is of a similar magnitude to murine models of the most extreme forms of monogenic obesity. These data identify TRβ in the VMH as a major physiological regulator of food intake and energy homeostasis.

Graphical Abstract

Highlights

• •

  The ventromedial hypothalamus (VMH) expresses thyroid hormone receptor beta (TRβ)

• •

  In mice, selective knockdown of TRβ (TRβ ⁻) in the VMH results in severe obesity

• •

  The obesity is due to overeating (hyperphagia) and reduced energy expenditure

• •

  TRβ ⁻ mice have altered expression of hypothalamic regulators of food intake

Abstract

Hameed et al. report that selective knockdown of a thyroid hormone receptor in the mouse hypothalamus results in a phenotype of severe obesity, overeating, and reduced energy expenditure, which may be due to downstream changes in the expression of hypothalamic regulators of food intake.