Thyroid Hormone Modulates Food Intake and Glycemia via Ghrelin Secretion in Zucker Fatty rats

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

T₃ - ghrelin-antagonist - MK-0677 - food intake - hyperglycemia

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