GSE98690
Thyroid hormone receptor beta in the ventromedial hypothalamus is essential for the physiological regulation of food intake and body weight
The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms which regulate appetite and body weight will provide the rationale for the design of novel anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TR) which function as ligand inducible transcription factors. The TR beta isoform (TRß) is expressed in the ventromedial hypothalamus (VMH), a brain area important for control of energy homeostasis. Here we report that selective knock down of TRß 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 TRß in the VMH as a major physiological regulator of food intake and energy homeostasis. Overall design: RNAseq analysis was performed using hypothalamic RNA from thyroid hormone receptor beta flox/flox mice stereotaxically injected with either a recombinant adeno-associated virus (rAAV) expressing a Cre-GFP fusion protein to generate mice with reduced thyroid hormone receptor beta (TRß) expression in the ventromedial hypthalamus (VMH-TRß-) mice, or controls injected with rAAV encoding GFP into the VMH (VMH-GFP).