Region-specific differences in brain melanocortin receptors in rats of the lean phenotype.
Region-specific differences in brain melanocortin receptors in rats of the lean phenotype.
复制标题
瘦表型大鼠大脑黑皮质素受体的区域特异性差异。
DOI：
10.1097/wnr.0b013e328354f5c1
复制
发表时间：
2012
期刊：
影响因子：
1.7
通讯作者：
Novak,ColleenM
中科院分区：
文献类型：
--
作者：
Shukla,Charu;Britton,StevenL;Koch,LaurenG;Novak,ColleenM
脑黑素皮质素（MC）系统是调节能量平衡的众多重叠系统之一；它由多肽组成，包括通过黑素皮质素受体（mcr）起作用的[α]-黑色素细胞刺激激素。在人类研究中，MC3R和MC4R的突变和多态性已被确定为导致肥胖的最常见遗传因素之一。众所周知，脑MC3R和MC4R调节能量消耗（EE）和食物摄入，但对脑MC5R知之甚少。为了验证脑MC调节身体活动（PA）和情感表达的假设，我们比较了一直表现出高水平和低水平“自发”每日PA的大鼠的脑MCR谱。与低活性大鼠相比，高活性大鼠大脑中mcr的mRNA表达增强，特别是室旁核（PVN）的MC3R和下丘脑皮层外侧周的MC4R和MC5R。接下来，我们将MCR激动剂黑色素素II微注射到PVN区域，并测量PA和EE。pvn内黑色素素II诱导了PA的剂量依赖性增加，这种影响在高活性大鼠中比在低活性大鼠中更大。这些结果表明，高PA中特定区域的脑MCR表达与高耐力能力有关，并确定了脑MC系统中可能有助于个体间能量平衡变化的有希望的靶点。
The brain melanocortin (MC) system is one of numerous overlapping systems regulating energy balance; it consists of peptides including [alpha]-melanocyte-stimulating hormone that act through melanocortin receptors (MCRs). Mutations and polymorphisms in MC3R and MC4R have been identified as one of the most common genetic contributors to obesity in human studies. Brain MC3R and MC4R are known to modulate energy expenditure (EE) and food intake, but much less is known regarding brain MC5R. To test the hypothesis that brain MC modulates physical activity (PA) and EE, we compared brain MCR profiles in rats that consistently show high versus low levels of ‘spontaneous’ daily PA. Compared with low-activity rats, high-activity rats show enhanced mRNA expression of MCRs in the brain, specifically of MC3R in the paraventricular nucleus (PVN), and MC4R and MC5R in the perifornical lateral hypothalamus. Next, we microinjected the MCR agonist melanotan II into the PVN region and measured PA and EE. Intra-PVN melanotan II induced a dose-dependent increase in PA and this effect was greater in high-activity rats compared with low-activity rats. These results indicate region-specific brain MCR expression in the heightened PA seen in association with high endurance capacity and identify promising targets in the brain MC system that may contribute to interindividual variability in energy balance.