Triiodothyronine Directly Regulates Feeding
NM Martin, WM Kong, KL Smith, JV Gardiner, CJ Small, MA Ghatei & SR Bloom
The increased appetite associated with hyperthyroidism is assumed to be secondary to an increased metabolic rate. However, the role of thyroid hormones in appetite regulation is poorly understood. We hypothesised that thyroid hormones directly regulate food intake and studied the effects of peripheral and CNS administration of tri-iodothyronine (T3) on food intake in male Wistar rats in vivo.
A single subcutaneous (s.c.) injection of 4.5 nmol per kilogram T3 doubled food intake 2 hours post-administration (1.2 plus/minus 0.3 [T3] versus 0.5 plus/minus 0.1 grams [control] P<0.05, n = 8 per group). This increase in food intake lasted for 8 hours. Plasma fT3 was 30 percent higher in the T3-treated group (P<0.001), yet plasma fT4 and TSH were unchanged compared to controls. This stimulation in feeding was not associated with behavioural change or altered energy expenditure. To investigate a CNS site of action of peripheral T3, we examined hypothalamic expression of the immediate early gene Egr-1. Peripheral injection of the same dose of T3 (4.5 nmol per kilogram) increased neuronal activation in the ventromedial nucleus (VMN) 2 hours post-administration (median and interquartile range: 1080 (879:1282) [T3] versus 642 (620:664) immunoreactive cells [vehicle], P<0.05, n = 6 per group). Intranuclear injection of T3 (0.5, 1, 5 or 50 pmol) into the VMN increased food intake at 1 hour (0-1h: 3.1 plus/minus 0.5 [50 pmol T3] versus 0.8 ± 0.2 grams [control], P<0.0001, n = 13-16 per group). No difference in food intake was observed at any further time-points. We have shown that peripheral and central administration of T3 stimulates feeding in rats. We propose a novel role for T3, in the direct regulation of food intake.