Center for Advanced Nutrition, Utah State Univ., 4715 Old Main Hill, Logan, UT 84322, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R385-93. doi: 10.1152/ajpregu.00591.2009. Epub 2009 Nov 18.
The amygdala is rich in melanocortin 4 receptors. Because the reduction in dietary fat intake after enterostatin is injected in the central nucleus of the amygdala (CeA) is blocked by a melanocortin 4 receptor antagonist, we investigated the role of melanocortin activity in the CeA in regulating food intake and macronutrient choice. Sprague-Dawley rats, fitted with CeA cannulas, were fed either chow, a high-fat (HF) diet, or adapted to a two-choice HF or low-fat (LF) diet. Injections of the MC4R agonist melanotan II (MTII) in the CeA had a dose-dependent inhibitory effect on food intake that lasted for at least 24 h. This response was greater in rats fed a HF diet. The inverse agonist agouti-related protein (AgRP) and antagonist SHU-9119 increased food intake in a dose-dependent manner, with the hyperphagia lasting for 60 h. In rats adapted to a two-choice HF/LF diet, MTII decreased HF consumption but had no effect on LF consumption, resulting in a long-lasting decrease in total calorie intake (-35.5% after 24 h, P < 0.05). Total calorie intake increased in both AgRP- and SHU-9119-treated rats (32 and 109% after 24 h, respectively) as the result of increased intake of HF diet. There was no modification of LF consumption with AgRP treatment and a transient nonsignificant decrease with SHU-9119 treatment. Amygdala brain-derived neurotrophic factor expression was increased by AgRP in fed rats. These results identify the amygdala as a site of action for the melanocortin system to control food intake and dietary preferences.
杏仁核富含黑色素皮质素 4 受体。由于在杏仁核中央核（CeA）注射肠抑胃肽后，饮食脂肪摄入量的减少被黑色素皮质素 4 受体拮抗剂阻断，因此我们研究了 CeA 中黑色素皮质素活性在调节食物摄入和宏量营养素选择中的作用。接受 CeA 套管的 Sprague-Dawley 大鼠喂食标准饮食、高脂肪（HF）饮食或适应两种选择的 HF 或低脂肪（LF）饮食。在 CeA 中注射 MC4R 激动剂黑色素浓蛋白 II（MTII）对食物摄入有剂量依赖性的抑制作用，至少持续 24 小时。在喂食 HF 饮食的大鼠中，这种反应更大。反向激动剂 agouti 相关蛋白（AgRP）和拮抗剂 SHU-9119 以剂量依赖性方式增加食物摄入，摄食持续 60 小时。在适应两种选择的 HF/LF 饮食的大鼠中，MTII 降低 HF 消耗，但对 LF 消耗没有影响，导致总热量摄入长期减少（24 小时后减少 35.5%，P<0.05）。AgRP 和 SHU-9119 处理的大鼠总热量摄入均增加（分别为 24 小时后增加 32%和 109%），原因是 HF 饮食摄入量增加。AgRP 处理对 LF 消耗没有影响，SHU-9119 处理时 LF 消耗短暂且无统计学意义降低。在喂食的大鼠中，AgRP 增加了杏仁核脑源性神经营养因子的表达。这些结果表明杏仁核是黑色素皮质素系统控制食物摄入和饮食偏好的作用部位。
