Hypothalamic localization of the feeding effect of agouti-related peptide and α-melanocyte-stimulating hormone
Hypothalamic localization of the feeding effect of agouti-related peptide and α-melanocyte-stimulating hormone
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DOI：
10.2337/diabetes.49.2.177
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发表时间：
2000-02-01
期刊：
影响因子：
7.7
通讯作者：
Bloom, SR
中科院分区：
文献类型：
--
作者：
Kim, MS;Rossi, M;Bloom, SR
下丘脑中的黑素皮质素-4受体(MC4R)被认为在食物摄入的生理调节中起着重要作用。通过使用内源性MC4R激动剂α-黑素细胞刺激素(α-MSH)和内源性MC4R拮抗剂刺鼠相关肽(AgRP)，我们研究了已知的表达MC4R的下丘脑区域参与了摄食调节。在大鼠下丘脑室旁核(PVN)、弓状核(Arc)、背内侧核(DMN)和腹内侧核(VMN)、内侧视前区(MPO)、下丘脑前区(AHA)和下丘脑外侧区(LHA)以及下丘脑杏仁核外中央核(CEA)内插入套管。给饲喂和禁食大鼠分别给予AgRP(83-132)(0.1nmol)和[NLE(4)，D-Phe(7)]-α-MSH(NDP-MSH)(0.1nmol)。PVN、DMN和MPO是对AgRP和NDP-MSH反应最强的区域。注射后8h，与生理盐水对照组相比，AgRP3个核团的摄食量分别增加218+/-23%(P<；0.005)、268+/-42%(P<；0.005)和236+/-31%(P<；0.01)。注射1h后，下丘脑室旁核摄食量减少52+/-6%(P<；0.005)，DMN减少44+/-6%(P<；0.0001)，MPO减少55+/-6%(P<；0.0001)。注射入AHA和CEA后，摄食量的变化较小。在给ARE、LHA或VMN注射AgRP后，没有观察到摄食的变化，但NDP-MSH抑制了ARE和LHA的摄食量。本研究表明，表达MC4R的下丘脑核团对AgRP和α-MSH的敏感性不同，这与它们的摄食效应有关。
The melanocortin-4 receptor (MC4R) in the hypothalamus is thought to be important in physiological regulation of food intake. We investigated which hypothalamic areas known to express MC4R are involved in the regulation of feeding by using alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous MC4R agonist, and agouti-related peptide (Agrp), an endogenous MC4R antagonist. Cannulae were inserted into the rat hypothalamic paraventricular (PVN), arcuate (Arc), dorsomedial (DMN), and ventromedial (VMN) nuclei; the medial preoptic (MPO), anterior hypothalamic (AHA), and lateral hypothalamic (LHA) areas; and the extrahypothalamic central nucleus of the amygdala (CeA). Agrp (83-132) (0.1 nmol) and [Nle(4), D-Phe(7)]-alpha-MSH (NDP-MSH) (0.1 nmol), a stable alpha-MSH analog, were administered to fed and fasted rats, respectively. The PVN, DMN, and MPO were the areas with the greatest response to Agrp and NDP-MSH. At 8 h postinjection, Agrp increased feeding in the PVN by 218 +/- 23% (P < 0.005), in the DMN by 268 +/- 42% (P < 0.005), and in the MPO by 236 +/- 31% (P < 0.01) compared with a saline control group for each nucleus. NDP-MSH decreased food intake in the PVN by 52 +/- 6% (P < 0.005), in the DMN by 44 +/- 6% (P < 0.0001), and in the MPO by 55 +/- 6% (P < 0.0001) at 1 h postinjection. Injection into the AHA and CeA resulted in smaller alterations in food intake. No changes in feeding were seen after the administration of Agrp into the Are, LHA, or VMN, but NDP-MSH suppressed food intake in the Are and LHA. This study indicates that the hypothalamic nuclei expressing MC4R vary in their sensitivity to Agrp and alpha-MSH with regard to their effect feeding.