Peptides that regulate food intake: regional, metabolic, and circadian specificity of lateral hypothalamic orexin A feeding stimulation.
Peptides that regulate food intake: regional, metabolic, and circadian specificity of lateral hypothalamic orexin A feeding stimulation.
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发表时间：
2003
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通讯作者：
A. Thorpe;M. Mullett;Chuanfeng Wang;C. Kotz
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作者：
A. Thorpe;M. Mullett;Chuanfeng Wang;C. Kotz
在外侧下丘脑（LH）给予食欲素A （OX-A）以剂量依赖的方式增加摄食。LH是一个相对较大的神经结构，具有神经输入、传出投射和食欲素受体分布的异质性。我们试图确定对OX-A注射液喂养刺激作用最敏感的LH区域。在56只雄性spraguedawley大鼠的四个单独的LH区域上方1mm处，分别在喙尾方向上约1mm处安装套管。LH区14 ~ 16只。恢复后，动物分别接受人工脑脊液或OX-A（250、500或1,000 pmol）。为了确定LH OX-A是否对摄食反应有昼夜效应，我们在0200,0900,1400和2100进行了注射。分别于注射后1、2、4 h测定摄食量。只有在LH的最吻侧部位注射OX-A能显著刺激摄食。在这个区域内，摄食在一天的任何时间都增加，尽管最强劲和显著的摄食反应发生在下午（1400）注射OX-A之后。为了确定大鼠的代谢状态在多大程度上影响了食欲素诱导进食的昼夜节律特异性，研究人员将动物置于限制饮食中，并在LH的最吻侧区域注射OX-A。在这些条件下，OX-A显著增加了动物的摄取量，与非限制饮食的动物相比，这种增加更为强劲。这些数据表明，吻侧LH是唯一对OX-A注射敏感的LH区域，注射时动物的代谢状态可能影响对OX-A的摄食反应。
Orexin A (OX-A) administered in the lateral hypothalamus (LH) increases feeding in a dose-dependent manner. The LH is a relatively large neural structure with a heterogeneous profile of neural inputs, efferent projections, and orexin receptor distribution. We sought to determine the LH region most sensitive to the feeding stimulatory effect of OX-A injection. Fifty-six male Sprague-Dawley rats were fitted with cannulas 1 mm above four separate LH regions approximately 1 mm apart in the rostral-caudal direction. There were 14-16 animals/LH region. After recovery, animals received either artificial cerebrospinal fluid or OX-A (250, 500, or 1,000 pmol). To determine whether there is a circadian effect of LH OX-A on the feeding response, we performed injections at 0200, 0900, 1400, and 2100. Food intake was measured at 1, 2, and 4 h after injection. The most rostral extent of the LH was the only region in which injection of OX-A significantly stimulated feeding. Within this region, feeding was increased at all times of the day, although the most robust and only significant feeding response occurred after the afternoon injection (1400) of OX-A. To determine the extent to which the metabolic status of the rat contributed to the circadian specificity of orexin-induced feeding, animals were placed on a restricted diet and injected with OX-A in the most rostral region of the LH. Under these conditions, OX-A significantly increased feeding and more robustly when compared with animals on a nonrestricted diet. These data suggest that the rostral LH is the only region of the LH sensitive to the injection of OX-A, and the metabolic status of the animal at the time of injection may influence the feeding response to OX-A.