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Neurocircuits linking thermoregulation and feeding

连接体温调节和进食的神经回路

基本信息

批准号：
10347362
负责人：
Jennifer Dezet Deem
金额：
$ 10.79万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10347362
关键词：
Acute Animals Behavioral Body Temperature Body Temperature Changes Body Weight Body Weight decreased Body fat Brain Coupled Coupling Cutaneous Data Defect Development Eating Energy Intake Energy Metabolism Environment Exposure to Fatty acid glycerol esters Fiber Functional disorder Future Goals High Fat Diet Homeostasis Hyperphagia Hypothalamic structure Impairment Internal Ribosome Entry Site Light Link Literature Mammals Maps Medial Dorsal Nucleus Modeling Modernization Mus Neurons Neurosciences Normal Range Obesity Peptides Photometry Physiologic Thermoregulation Physiological Play Population Preoptic Areas Process Reporting Role Secondary to Societies Structure of nucleus infundibularis hypothalami System Techniques Temperature Thermogenesis Time Tyrosine 3-Monooxygenase Work base cost diet-induced obesity energy balance excessive weight gain falls feeding in vivo metabolic phenotype neural circuit neuronal circuitry novel novel strategies obesity treatment optogenetics paraventricular nucleus pituitary adenylate cyclase activating polypeptide preservation response

项目摘要

Project Summary The tight coupling of thermoregulation to energy homeostasis allows body temperature and body weight to be defended, despite dramatic changes in ambient temperature. A central goal of this proposal is to clarify how adaptive changes in energy intake are coupled to changes in ambient temperature, with a focus on the hyperphagic response to cold exposure. Although untested, it has been an accepted view that cold-induced hyperphagia is initiated following the development of a negative energy state (i.e., a loss of body fat stores). However, our recent findings demonstrate that food intake and increases in heat production occur rapidly and in parallel following acute cold exposure, and likely precede the development of a negative energy state. Also, we find our recent findings implicate a role for agouti-related peptide (Agrp) neurons in the adaptive feeding response since increases of Agrp neuron activity precede and are required for cold-induced hyperphagia, but not cold-induced thermogenic responses. Here, we propose the novel and interrelated hypotheses that cold- induced activation of thermoregulatory circuits drive adaptive changes of both energy expenditure and food intake concurrently, that these responses occur independently of and serve to minimize changes in energy balance, and that they are uncoupled in obese animals, leading to weight loss. The overarching goal of the proposal is to identify and functionally characterize the neurocircuitry linking thermoregulation to control of Agrp neuronal activity and associated feeding responses. Studies proposed herein will, therefore, shed new light not only on how energy homeostasis and food intake are coupled to one another, but how this coupling process becomes disrupted in obese animals. Proposed studies seek 1) to characterize neurocircuits that link thermoregulation to Agrp neuron activation and cold-induced hyperphagia and 2) to determine how neuronal and circuit-level dysfunction occurs following the introduction of a high-fat diet. To accomplish this, we will use state-of-the-art neuroscience techniques including chemogenetics, optogenetics, and in vivo fiber photometry approaches are utilized, in combination with immunohistochemical and advanced metabolic phenotyping. Together, this work will advance the understanding of the neurocircuitry linking thermoregulation to Agrp neuronal activity and feeding and may identify novel strategies for the treatment of obesity.

项目总结