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

探索维生素 D 对饮食工业影响的神经和分子基础

• 批准号: 8479354
• 负责人: RALPH J DILEONE
• 金额: $ 17.12万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8479354
• 关键词: Animal Behavior; Animals; Behavior; Behavioral; Binding; Biology; Blood; Body Weight; Body Weight decreased; Brain; Brain region; Calories; Carbohydrates; Cell Nucleus; Complex; Data; Developed Countries; Development; Diet; Dietary Factors; Drug Addiction; Eating; Eating Behavior; Environment; Etiology; Evaluation; Evolution; Fatty acid glycerol esters; Food; Food Intake Regulation; Gene Expression; Gene Targeting; Genes; Genetic Transcription; Health; Healthcare Systems; Hormones; Individual; Industry; Intake; Laboratory Animal Models; Leptin; Macronutrients Nutrition; Metabolic; Molecular; Mus; Neurons; Obesity; Pathway interactions; Plant Roots; Population; Process; Proteins; Quality of life; Regulation; Research; Rewards; Role; Self-control as a personality trait; Signal Transduction; Source; Steroid Receptors; Sum; System; Testing; United States; VDR gene; Variant; Ventral Tegmental Area; Vitamin D; Vitamin D3 Receptor; Vitamins; Weight; Western Europe; Work; base; bone; cost; dopamine system; drug of abuse; feeding; fitness; interest; mesolimbic system; motivated behavior; mouse model; neural circuit; neuromechanism; novel; obesity prevention; receptor; relating to nervous system; research study; response; steroid hormone; transcription factor

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.

描述（由申请人提供）：肥胖及其健康后果在成本和生活质量方面都很重要。 饮食和体重都受到基因的影响，同时对环境也很敏感。 膳食组成是一个可以影响摄入量的环境变量，但具体机制尚不清楚。 同样，虽然该领域在确定可以改变食物摄入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。 维生素D水平与肥胖率呈负相关，这增加了维生素D直接影响摄入量的可能性。 然而，还没有提出任何机制，关于维生素D对神经功能的影响也知之甚少。 目前的提议证明了一种新的小鼠模型，其中低维生素D水平放大了在延长高脂肪饮食摄入期间观察到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脑奖励中心的维生素D信号的影响。 拟议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。 这项工作至关重要，因为它直接测试了饮食环境如何影响摄入量和体重的假设和机制。

项目成果

Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.

• DOI: 10.1523/eneuro.0122-15.2016
• 发表时间: 2016-03
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Trinko JR;Land BB;Solecki WB;Wickham RJ;Tellez LA;Maldonado-Aviles J;de Araujo IE;Addy NA;DiLeone RJ
• 通讯作者: DiLeone RJ