Triiodothyronine stimulates food intake via the hypothalamic ventromedial nucleus independent of changes in energy expenditure.

Increased food intake is characteristic of hyperthyroidism, although this is presumed to compensate for a state of negative energy balance. However, here we show that the thyroid hormone T(3) directly stimulates feeding at the level of the hypothalamus. Peripheral administration of T(3) doubled food intake in ad libitum-fed rats over 2 h and induced expression of the immediate early gene, early growth response-1, in the hypothalamic ventromedial nucleus (VMN), whereas maintaining plasma-free T(3) levels within the normal range. T(3)-induced feeding occurred without altering energy expenditure or locomotion. Injection of T(3) directly into the VMN produced a 4-fold increase in food intake in the first hour. The majority of T(3) in the brain is reported to be produced by tissue-specific conversion of T(4) to T(3) by the enzyme type 2 iodothyronine deiodinase (D2). Hypothalamic D2 mRNA expression showed a diurnal variation, with a peak in the nocturnal feeding phase. Hypothalamic D2 mRNA levels also increased after a 12- and 24-h fast, suggesting that local production of T(3) may play a role in this T(3) feeding circuit. Thus, we propose a novel hypothalamic feeding circuit in which T(3), from the peripheral circulation or produced by local conversion, stimulates food intake via the VMN.