Neural determinants on meal size in invertebrate models of obesity

无脊椎动物肥胖模型中膳食量的神经决定因素

基本信息

  • 批准号:
    10518734
  • 负责人:
  • 金额:
    $ 39.07万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-01 至 2027-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY During eating animals modulate the size of meals by associating sensory cues with rewarding qualities of food. This process is central to the control of food intake and is impaired in humans and animals exposed to high fat and sugar diets. The neural mechanisms through which food associations 1) regulate meal size and 2) are perturbed by this dietary environment, however, remain poorly understood. This lack of knowledge has hindered progress in uncovering the underlying causes of obesity and, thus, in curbing the spread of metabolic disease. Here we propose to use the D. melanogaster model to address the need for mechanistic studies on the neural regulation and deregulation of meal size. A diet high in sugar promotes higher intake and obesity in flies, but unlike vertebrate models, the neural circuits involved in food associations converge onto a single brain region; further, transgenic tools to manipulate and visualize these circuits are publicly available, thanks to decades of research and the connectome. Our long term goal is to use the unique advantages of the fly model to uncover how food environments high in sugar and fat promote obesity and metabolic disease. Our central hypothesis is that diet-driven changes in dopamine transmission underlie the increase in meal size observed in animals fed high-calorie diets. This hypothesis is based on our published and unpublished data showing a causal link between the dopaminergic processing of taste and nutrient qualities, the formation of food associations, and intake. To test this idea we will use in vivo imaging of calcium and dopamine signals, behavioral assays, metabolic measurements, and optogenetic manipulations of dopaminergic, associative learning, and premotor circuits to define both the causes of impaired food associations (Aim 1) and their consequences on meal size (Aim 2). The successful completion of the proposed studies will define how food associations control intake and the extent through which diet-dependent alterations in DA signaling impact this process; this will illuminate the neural mechanisms that regulate meal size and uncover how they are deregulated by the food environment. Together, this will help advance our understanding of the causes of obesity, which is key to the NIDDK mission of decreasing the burden and spread of metabolic disease.
项目概要 在进食过程中,动物通过将感官线索与奖励品质联系起来来调节膳食的大小。 食物。这一过程对于控制食物摄入至关重要,并且在暴露于食物摄入的人类和动物中会受到损害。 高脂肪和高糖饮食。食物关联的神经机制 1) 调节膳食量 2) 然而,人们对这种饮食环境的困扰仍然知之甚少。这种知识的缺乏已经 阻碍了揭示肥胖根本原因的进展,从而阻碍了遏制代谢性疾病蔓延的进展 疾病。在这里,我们建议使用黑腹果蝇模型来解决机械研究的需要 神经调节和膳食量的放松调节。高糖饮食会导致摄入量增加和肥胖 苍蝇,但与脊椎动物模型不同的是,参与食物关联的神经回路集中在一个单一的神经回路上。 大脑区域;此外,操纵和可视化这些电路的转基因工具是公开可用的,这要归功于 数十年的研究和连接组。我们的长期目标是利用飞行模型的独特优势 揭示高糖和高脂肪的食物环境如何促进肥胖和代谢疾病。我们的中央 假设是饮食驱动的多巴胺传递变化是观察到的膳食量增加的基础 动物喂食高热量饮食。该假设基于我们已发表和未发表的数据,显示 味道和营养品质的多巴胺能加工之间的因果关系,食物的形成 关联和摄入量。为了测试这个想法,我们将使用钙和多巴胺信号的体内成像, 多巴胺能、联想的行为测定、代谢测量和光遗传学操作 学习和运动前回路来定义食物关联受损的原因(目标 1)及其 对膳食量的影响(目标 2)。拟议研究的成功完成将确定食品如何 协会控制摄入量以及饮食依赖性 DA 信号改变影响的程度 过程;这将阐明调节膳食大小的神经机制并揭示它们是如何运作的 食品环境放松管制。总之,这将有助于加深我们对造成这种情况的原因的理解。 肥胖是 NIDDK 减轻代谢疾病负担和传播使命的关键。

项目成果

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Monica Dus其他文献

Monica Dus的其他文献

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{{ truncateString('Monica Dus', 18)}}的其他基金

The role of neuroepigenetics in bidirectional behavioral states
神经表观遗传学在双向行为状态中的作用
  • 批准号:
    9167992
  • 财政年份:
    2016
  • 资助金额:
    $ 39.07万
  • 项目类别:
Neural and molecular mechanisms of glucosensation mediating food choice behavior
葡萄糖酸化介导食物选择行为的神经和分子机制
  • 批准号:
    9068114
  • 财政年份:
    2015
  • 资助金额:
    $ 39.07万
  • 项目类别:
Neural and molecular mechanisms of glucosensation mediating food choice behavior
葡萄糖酸化介导食物选择行为的神经和分子机制
  • 批准号:
    9242019
  • 财政年份:
    2015
  • 资助金额:
    $ 39.07万
  • 项目类别:
Mechanisms of glucosensation mediating food choice behavior in Drosophila
葡萄糖酸化介导果蝇食物选择行为的机制
  • 批准号:
    8423858
  • 财政年份:
    2013
  • 资助金额:
    $ 39.07万
  • 项目类别:
Neural and molecular mechanisms of glucosensation mediating food choice behavior
葡萄糖酸化介导食物选择行为的神经和分子机制
  • 批准号:
    8713989
  • 财政年份:
    2013
  • 资助金额:
    $ 39.07万
  • 项目类别:

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