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
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
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DOI：
10.1159/000074885
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发表时间：
2003-01-01
影响因子：
4.1
通讯作者：
Oikawa, S
中科院分区：
文献类型：
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作者：
Ishii, S;Kamegai, J;Oikawa, S
食物摄入受到下丘脑神经肽的调节，该神经肽对外周信号做出反应。血浆生长素释放肽和瘦素水平反映外周能量平衡并调节下丘脑神经肽，例如神经肽 Y (NPY)、阿片黑皮素原 (POMC)、可卡因和安非他明调节转录物 (CART)、黑色素浓缩激素 (MCH) 和食欲素。甲状腺激素刺激人类和啮齿动物的食物摄入。然而，造成这种刺激的机制尚未完全阐明。为了研究对三碘甲状腺原氨酸 (T-3) 诱导的甲状腺毒症的食欲亢进反应，在每天腹腔注射 T-3 或媒介物 7 天后对成年雄性大鼠进行了研究。 T-3治疗的大鼠明显食欲亢进。在进食过量期间，血浆瘦素水平显着降低。然而，胃中生长素释放肽基因的表达和血浆生长素释放肽浓度在两组之间没有差异。在 T-3 治疗的大鼠中，下丘脑 NPY mRNA 水平显着增加，并与下丘脑 POMC 和 CART mRNA 水平显着降低相关。两组之间的下丘脑 MCH 和食欲素 mRNA 水平没有差异。此外，脑室内注射 NPY Y1 受体拮抗剂 BIBO3304 可部分逆转食欲过盛。因此，血浆瘦素水平降低可能导致 T-3 诱导的甲状腺毒症中的食欲亢进。然而，血浆生长素释放肽水平并不会导致这种食欲亢进。版权所有 (C) 2003 S. Karger AG，巴塞尔。
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. Copyright (C) 2003 S. Karger AG, Basel.