Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats.
Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats.
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DOI：
10.1016/j.neuroscience.2015.09.035
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发表时间：
2015-12-03
期刊：
影响因子：
3.3
通讯作者：
Novak CM
中科院分区：
文献类型：
--
作者：
Shukla C;Koch LG;Britton SL;Cai M;Hruby VJ;Bednarek M;Novak CM
身体活动和非运动活动产热（NEAT）是造成个体体重差异的关键因素，与遗传易感性相互作用。在大脑中，许多神经内分泌中间体调节食物摄入和能量消耗（EE）;这包括大脑黑皮质素（MC）系统，由黑皮质素肽及其受体（MCR）组成。MC 3R和MC 4 R已成为EE和食物摄入的关键调节剂。要确定如何在MC信号的差异可能是个体差异的基础上的体力活动水平，我们研究了行为反应MC受体激动剂和拮抗剂在大鼠表现出高和低水平的体力活动和NEAT，即，高和低容量的跑步者（HCR，LCR），开发的差异内在有氧跑步能力的人工选择。集中在下丘脑，我们确定了大脑区域特异性升高的MCR 3，4，以及MC 5 R的表达，在高度活跃，瘦HCR相对于不太活跃和肥胖倾向的LCR。此外，使用特异性激动剂和拮抗剂激活或抑制MCR导致的活性和相关EE差异具有相似的区域特异性，并直接对应于差异MCR表达模式。这里研究的激动剂和拮抗剂在所用剂量下对食物摄入量没有显著影响，表明受体表达的差异模式对体力活动比能量平衡调节的其他方面更有意义。因此，MCR介导的体力活动可能是区分瘦型的关键神经机制，也是增强体力活动和NEAT的靶点。
Physical activity and non-exercise activity thermogenesis (NEAT) are crucial factors accounting for individual differences in body weight, interacting with genetic predisposition. In the brain, a number of neuroendocrine intermediates regulate food intake and energy expenditure (EE); this includes the brain melanocortin (MC) system, consisting of melanocortin peptides as well as their receptors (MCR). MC3R and MC4R have emerged as critical modulators of EE and food intake. To determine how variance in MC signaling may underlie individual differences in physical activity levels, we examined behavioral response to MC receptor agonists and antagonists in rats that show high and low levels of physical activity and NEAT, that is, high- and low-capacity runners (HCR, LCR), developed by artificial selection for differential intrinsic aerobic running capacity. Focusing on the hypothalamus, we identified brain region-specific elevations in expression of MCR 3, 4, and also MC5R, in the highly active, lean HCR relative to the less active and obesity-prone LCR. Further, the differences in activity and associated EE as a result of MCR activation or suppression using specific agonists and antagonists were similarly region-specific and directly corresponded to the differential MCR expression patterns. The agonists and antagonists investigated here did not significantly impact food intake at the doses used, suggesting that the differential pattern of receptor expression may by more meaningful to physical activity than to other aspects of energy balance regulation. Thus, MCR-mediated physical activity may be a key neural mechanism in distinguishing the lean phenotype and a target for enhancing physical activity and NEAT.