Function of neuropeptide Y and agouti-related protein at weaning: relation to corticosterone, dietary carbohydrate and body weight

Function of neuropeptide Y and agouti-related protein at weaning: relation to corticosterone, dietary carbohydrate and body weight
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DOI:
10.1016/j.brainres.2004.12.038
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发表时间:
2005-03-02
期刊:
影响因子:
2.9
通讯作者:
Chang, GQ
Chang, GQ
中科院分区:
医学3区
文献类型:
--
作者:
Leibowitz, SF;Sepiashvili, K;Chang, GQ

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神经肽 Y (NPY) 和刺豚鼠相关蛋白 (AgRP) 是进食的有效刺激物,在成年大鼠中与皮质酮 (CORT) 和膳食碳水化合物有关。为了了解生命早期这种关系的重要性,在断奶前后的不同年龄,对给予选择常量营养素饮食或维持富含碳水化合物饮食的大鼠进行了这些参数的测量。结果表明,在雄性和雌性幼鼠中,与断奶前的 P15 和断奶后的 P27 相比,弓状核 (ARC) 中 NPY 和 AgRP 的表达和产生在出生后第 21 天 (P21) 达到峰值。这些升高的肽水平与 CORT 和葡萄糖的峰值水平以及断奶时对碳水化合物的强烈自然偏好有关,碳水化合物占幼犬总饮食的 55-65%。在按这些阶段体重定义的亚组中,体重仅降低 4% 的大鼠(与体重较高的幼鼠相比)的 ARC 中 NPY 和 AgRP 表达增加 30-60%,CORT 水平升高,而瘦素或胰岛素没有差异。这种反应在 P21 时比 P15 或 P27 时明显更明显。额外的结果显示,与 45% 碳水化合物饮食相比,65% 碳水化合物饮食饲养的 P27 幼崽的 NPY 表达、CORT 水平、体重和腹股沟脂肪垫重量有所升高,这表明了碳水化合物在此阶段的重要性。这些结果表明,下丘脑 NPY 和 AgRP 与 CORT 一起具有葡萄糖调节和喂养刺激功能,有助于介导从富含脂肪饮食的哺乳到独立喂养富含碳水化合物的饮食的转变。在此关键时期,碳水化合物与肽和 CORT 一起提供重要信号,包括升高的葡萄糖,促进脂肪从头生成,并使断奶动物能够在食物匮乏的时期生存下来。 (c) 2005 Elsevier B.V. 保留所有权利。
Neuropeptide Y (NPY) and agouti-related protein (AgRP), potent stimulants of feeding, have been linked in adult rats to both corticosterone (CORT) and dietary carbohydrate. To understand the significance of this relationship early in life, measurements were taken of these parameters at different ages around weaning, in rats given a choice of macronutrient diets or maintained on a carbohydrate-rich diet. The results demonstrate that, in both male and female rat pups, the expression and production of NPY and AgRP in the arcuate nucleus (ARC) peak on postnatal day 21 (P21), compared to P15 before weaning and P27 after weaning. These elevated levels of peptide were associated with peak levels of CORT and glucose and also a strong, natural preference for carbohydrate at weaning, which accounted for 55-65% of the pups' total diet. In subgroups defined by their body weight at these stages, rats with as little as 4% lower body weight (compared to higher weight pups) had 30-60% greater expression of NPY and AgRP in the ARC and elevated levels of CORT, with no difference in leptin or insulin. This response was significantly more pronounced at P21 than at P15 or P27. The importance of carbohydrate during this stage was suggested by additional results showing elevated NPY expression, CORT levels, body weight and inguinal fat pad weights in P27 pups raised on a 65% carbohydrate diet vs. 45% carbohydrate. These results suggest that hypothalamic NPY and AgRP, together with CORT, have glucoregulatory as well as feeding stimulatory functions that help mediate the transition from suckling of a fat-rich diet to independent feeding of a carbohydrate-rich diet. During this critical period, the carbohydrate together with the peptides and CORT provide the important signals, including elevated glucose, that promote de novo lipogenesis and enable weanling animals to survive periods of food deprivation. (c) 2005 Elsevier B.V. All rights reserved.