Abstract
Hyperthyroidism is known to increase food intake and central administration of thyroid
hormone shows acute orexigenic effects in rodents. We investigated whether T3 influences appetite and glucose homeostasis by modulating circulating ghrelin, an
important orexigenic hormone, in Zucker fatty rats. The acute anorectic effects of
T3 and ghrelin mimetic MK-0677 were studied in rats trained for fasting induced food
intake. The serum concentration of T3, ghrelin, glucose, triglycerides, and liver glycogen were estimated. The involvement
of sympathetic nervous system was evaluated by conducting similar experiments in vagotomized
rats. T3 increased food intake and glucose in rats over 4 h, with increase in serum T3 and decrease in liver glycogen. T3 treatment was associated with increase in serum ghrelin. An additive effect on appetite
and glucose was observed when T3 (oral) was administered with central (intracerebroventricular) administration of
a ghrelin mimetic, MK-0677. Ghrelin antagonist, compound 8a, antagonized the hyperglycemic
and hyperphagic effects of T3. In vagotomized rats, T3 did not show increase in appetite as well as glucose. Serum ghrelin levels were unchanged
in these animals after T3 treatment. However, T3 showed increase in serum triglyceride levels indicating its peripheral lipolytic
effect, in vagotomized as well as sham treated animals. To conclude, acute orexigenic
and hyperglycemic effects of T3 are associated with ghrelin secretion and activity. This effect seems to be mediated
via vagus nerves, and is independent of glucoregulatory hormones.
Key words
T
3
- ghrelin-antagonist - MK-0677 - food intake - hyperglycemia
