权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
Monica Dus
金额：
$ 39.07万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
https://reporter.nih.gov/project-details/10518734
关键词：
Address Affect American Animals Appetitive Behavior Behavior Behavioral Assay Body Weight Brain Brain region Calcium Calories Chronic Disease Consumption Cues Data Development Diet Dopamine Eating Environment Etiology Exposure to Fatty acid glycerol esters Feeding behaviors Food Functional Imaging Future Genetic Goals Human Impairment Intake Invertebrates Knowledge Learning Life Expectancy Light Link Mammals Measurement Memory Metabolic Metabolic Diseases Metabolic syndrome Mission Modeling Mushroom Bodies National Institute of Diabetes and Digestive and Kidney Diseases Neurons Nutrient Obesity Output Play Process Property Psychological reinforcement Publishing Research Rewards Role Sensory Signal Transduction Sodium Chloride System Taste Perception Testing Transgenic Organisms Vertebrates Weight Gain Work base classical conditioning connectome density dietary dopaminergic neuron expectation experience experimental study fly food consumption food environment food quality high body mass index in vivo calcium imaging in vivo imaging learning network neural circuit neurochemistry neurogenetics neuromechanism neuroregulation obesogenic optogenetics prevent recruit relating to nervous system sensor sugar tool transmission 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