Hypothalamic Neuropeptide Y/Y1 Receptor Pathway Activated by a Reduction in Circulating Leptin, but Not by an Increase in Circulating Ghrelin, Contributes to Hyperphagia Associated with Triiodothyronine-Induced Thyrotoxicosis

• Published in: Neuroendocrinology Vol. 78; no. 6; pp. 321 - 330
• Main Authors: Ishii, Shinya, Kamegai, Jun, Tamura, Hideki, Shimizu, Takako, Sugihara, Hitoshi, Oikawa, Shinichi
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.12.2003; S. Karger AG
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Biological and medical sciences; Body Weight - drug effects; Eating - drug effects; Energy Metabolism - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression; Ghrelin; Hyperphagia - chemically induced; Hyperphagia - metabolism; Hypothalamus - metabolism; Leptin - blood; Male; Nerve Tissue Proteins - genetics; Neuroendocrine Effects of Leptin; Neuropeptide Y - genetics; Peptide Hormones - blood; Pro-Opiomelanocortin - genetics; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y - antagonists & inhibitors; Receptors, Neuropeptide Y - metabolism; Stomach - metabolism; Thyrotoxicosis - chemically induced; Thyrotoxicosis - metabolism; Triiodothyronine - blood; Triiodothyronine - pharmacology; Vertebrates: endocrinology; Neuropeptide Y; Feeding behavior; Ghrelin; Leptin; Neuropeptide Y receptors; Thyroid hormones; Pro-opiomelanocortin; Cocaine- and amphetamine-regulated transcript; Y1 neuropeptide Y receptor; Central nervous system; Thyroid hormone; Triiodothyronine; Hypothalamus; Hyperphagia; Encephalon
• ISSN: 0028-3835; 1423-0194
• DOI: 10.1159/000074885

Food intake is regulated by hypothalamic neuropeptides which respond to peripheral signals. Plasma ghrelin and leptin levels reflect peripheral energy balance and regulate hypothalamic neuropeptides such as neuropeptide Y (NPY), pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH), and orexins. Thyroid hormone stimulates food intake in humans and rodents. However, the mechanisms responsible for this stimulation have not been fully elucidated. To investigate the hyperphagic response to triiodothyronine (T 3 )-induced thyrotoxicosis, adult male rats were studied 7 days after daily intraperitoneal injections of T 3 or vehicle. T 3 -treated rats were markedly hyperphagic. During this hyperphagia, plasma leptin levels were markedly decreased. However, the expression of the ghrelin gene in the stomach and the plasma ghrelin concentrations did not differ between the 2 groups. Hypothalamic NPY mRNA levels were significantly increased and associated with a marked decreased in both hypothalamic POMC and CART mRNA levels in the T 3 -treated rats. Hypothalamic MCH and orexin mRNA levels did not differ between the 2 groups. In addition, hyperphagia was partially reversed by intracerebroventricular administration of the NPY Y1 receptor antagonist BIBO3304. Therefore, the decreased plasma leptin levels could contribute to hyperphagia in T 3 -induced thyrotoxicosis. However, plasma ghrelin levels did not contribute to this hyperphagia.