Neuroscience Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, State University of New York, Buffalo, NY, USA.
Exp Physiol. 2020 Jun;105(6):1012-1024. doi: 10.1113/EP088356. Epub 2020 May 13.
What is the central question of this study? We tested whether intra-nucleus accumbens core amylin receptor (AmyR) activation suppresses feeding and evaluated whether intake of palatable food influences mesocorticolimbic AmyR expression. What is the main finding and its importance? Intra-nucleus accumbens core AmyR activation reduces food intake in some dietary conditions. We showed that all components of the AmyR are expressed in the prefrontal cortex and central nucleus of the amygdala and demonstrated that access to fat impacts AmyR expression in these and other mesocorticolimbic nuclei. These results suggest that the intake of palatable food might alter amylin signalling in the brain and shed further light onto potential sites of action for amylin.
Amylin is a pancreas- and brain-derived peptide that acts within the CNS to promote negative energy balance. However, our understanding of the CNS sites of action for amylin remains incomplete. Here, we investigate the effect of amylin receptor (AmyR) activation in the nucleus accumbens core (NAcC) on the intake of bland and palatable foods. Intra-NAcC injection of the AmyR agonist salmon calcitonin or amylin itself in male chow-fed rats had no effect on food intake, meal size or number of meals. However, in chow-fed rats with access to fat solution, although fat intake was not affected by intra-NAcC AmyR activation, subsequent chow intake was suppressed. Given that mesolimbic AmyR activation suppresses energy intake in rats with access to fat solution, we tested whether fat access changes AmyR expression in key mesocorticolimbic nuclei. Fat exposure did not affect NAcC AmyR expression, whereas in the accumbens shell, expression of receptor activity modifying protein (RAMP) 3 was significantly reduced in fat-consuming rats. We show that all components of AmyRs are expressed in the medial prefrontal cortex and central nucleus of the amygdala; fat access significantly reduced expression of calcitonin receptor-A in the central nucleus of the amygdala and RAMP2 in the medial prefrontal cortex. Taken together, these results indicate that intra-NAcC AmyR activation can suppress energy intake and, furthermore, suggest that AmyR signalling in a broader range of mesocorticolimbic sites might have a role in mediating the effects of amylin on food intake and body weight.
本研究的核心问题是什么？我们测试了伏隔核核心内淀粉样肽受体（AmyR）的激活是否抑制摄食，并评估了可口食物的摄入是否会影响中脑边缘皮质内的 AmyR 表达。主要发现及其重要性是什么？伏隔核核心内 AmyR 的激活可减少某些饮食条件下的食物摄入。我们表明，前扣带回皮质和杏仁中央核中均表达了 AmyR 的所有成分，并证明了脂肪的摄入会影响这些核及其他中脑边缘皮质核中 AmyR 的表达。这些结果表明，可口食物的摄入可能会改变大脑中的淀粉样肽信号，并进一步揭示了淀粉样肽作用的潜在部位。
淀粉样肽是一种由胰腺和大脑衍生的肽，在中枢神经系统中发挥作用以促进负性能量平衡。然而，我们对淀粉样肽在中枢神经系统中的作用部位的理解仍不完整。在这里，我们研究了伏隔核核心（NAcC）内 AmyR 激活对平淡和可口食物摄入的影响。在雄性正常饮食喂养的大鼠中，向 NAcC 内注射 AmyR 激动剂鲑鱼降钙素或淀粉样肽本身对食物摄入、进餐量或进餐次数均没有影响。然而，在正常饮食喂养且可获得脂肪溶液的大鼠中，尽管 NAcC 内 AmyR 激活对脂肪摄入没有影响，但随后的正常饮食摄入却受到抑制。鉴于中脑边缘 AmyR 激活可抑制摄入脂肪溶液的大鼠的能量摄入，我们测试了脂肪暴露是否会改变关键中脑边缘皮质核中的 AmyR 表达。脂肪暴露并未影响 NAcC AmyR 的表达，而在伏隔核壳中，在摄入脂肪的大鼠中，受体活性修饰蛋白（RAMP）3 的表达显著降低。我们表明，AmyR 的所有成分均表达于内侧前额皮质和杏仁中央核；脂肪暴露显著降低了杏仁中央核中降钙素受体-A 的表达和内侧前额皮质中 RAMP2 的表达。综上所述，这些结果表明，NAcC 内 AmyR 的激活可抑制能量摄入，并且进一步表明，AmyR 信号在更广泛的中脑边缘皮质部位可能在介导淀粉样肽对食物摄入和体重的影响方面发挥作用。
