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
- 来源:
- 关键词:AddressAffectAmericanAnimalsAppetitive BehaviorBehaviorBehavioral AssayBody WeightBrainBrain regionCalciumCaloriesChronic DiseaseConsumptionCuesDataDevelopmentDietDopamineEatingEnvironmentEtiologyExposure toFatty acid glycerol estersFeeding behaviorsFoodFunctional ImagingFutureGeneticGoalsHumanImpairmentIntakeInvertebratesKnowledgeLearningLife ExpectancyLightLinkMammalsMeasurementMemoryMetabolicMetabolic DiseasesMetabolic syndromeMissionModelingMushroom BodiesNational Institute of Diabetes and Digestive and Kidney DiseasesNeuronsNutrientObesityOutputPlayProcessPropertyPsychological reinforcementPublishingResearchRewardsRoleSensorySignal TransductionSodium ChlorideSystemTaste PerceptionTestingTransgenic OrganismsVertebratesWeight GainWorkbaseclassical conditioningconnectomedensitydietarydopaminergic neuronexpectationexperienceexperimental studyflyfood consumptionfood environmentfood qualityhigh body mass indexin vivo calcium imagingin vivo imaginglearning networkneural circuitneurochemistryneurogeneticsneuromechanismneuroregulationobesogenicoptogeneticspreventrecruitrelating to nervous systemsensorsugartooltransmission process
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.
项目总结
项目成果
期刊论文数量(0)
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Monica Dus其他文献
Monica Dus的其他文献
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{{ item.author }}
{{ 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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