Exploring the neural and molecular basis for the effects of vitamin D on diet-ind

描述(由申请人提供)：肥胖及其对健康的影响在成本和生活质量方面都是重要的。饮食和体重都受到基因的影响，同时也明显对环境敏感。饮食构成是一个环境变量，可以影响摄入量，但具体机制尚不清楚。同样，尽管该领域在识别可以改变食物摄入量的关键分子和大脑区域方面取得了进展，但我们缺乏相关饮食变量如何与这些大脑系统相互作用的好例子。众所周知，维生素D水平与肥胖率呈负相关，这增加了这种维生素直接影响摄入量的可能性。然而，目前还没有机制被提出，关于维生素D对神经元功能的影响也知之甚少。目前的建议展示了一种新的小鼠模型，在这种模型中，低维生素D水平会放大在长期摄入高脂肪饮食时出现的食物摄入量和体重的增加。此外，初步数据表明，高脂饮食对中脑边缘奖励中心维生素D信号的影响。拟议中的实验将直接测试中脑边缘回路在维生素D反应中的作用，并表征维生素D受体如何改变神经元中的基因表达。这项工作是至关重要的，因为它直接测试关于饮食环境如何影响摄入量和体重的假设和机制。

DESCRIPTION (provided by applicant): Obesity and its health consequences are significant both in terms of cost and quality of life. Eating and body weight are both genetically influenced while also clearly sensitive to the environment. Dietary composition is an environmental variable that can influence intake but specific mechanisms are poorly defined. Likewise, while the field has made progress in identifying key molecules and brain regions that can alter food intake, we lack good examples of how relevant dietary variables can interact with these brain systems. Vitamin D levels are known to correlate inversely with obesity rates raising the possibility that this vitamin can influence intake directly. However, no mechanisms have been proposed and little is known about vitamin D effects on neuronal function. The current proposal demonstrates a novel mouse model where low vitamin D levels amplify increases in food intake and weight seen during extended intake of a high-fat diet. Moreover, preliminary data suggest effects of high-fat diet on vitamin D signaling in mesolimbic brain reward centers. The proposed experiments will directly test the role of mesolimbic circuits in vitamin D response and characterize how the vitamin D receptor alters gene expression in neurons. This work is critical as it directly tests hypotheses and mechanisms as to how the dietary environment influences intake and body weight.