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Drug Res (Stuttg) 2014; 64(10): 523-529
DOI: 10.1055/s-0033-1363222
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

K. Patel
1   Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India
,
A. Joharapurkar
1   Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India
,
N. Dhanesha
1   Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India
,
V. Patel
1   Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India
,
S. Kshirsagar
1   Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India
,
P. Raval
2   Department of Medicinal Chemistry, Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India
,
S. Raval
2   Department of Medicinal Chemistry, Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India
,
M. R. Jain
1   Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India
› Author Affiliations
Further Information

Publication History

received 15 October 2013

accepted 25 November 2013

Publication Date:
19 December 2013 (online)

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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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