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Integration of Feeding Time and Glucose Metabolism by the Circadian Gene Network

昼夜节律基因网络整合进食时间和葡萄糖代谢

基本信息

批准号：
10668512
负责人：
Joseph Bass
金额：
$ 48.65万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
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：
2021-09-17 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10668512
关键词：
Ablation Automobile Driving B-Lymphocytes Behavior Behavioral Beta Cell Brain Carbohydrates Cell physiology Cells Chromatin Circadian Rhythms Consumption Cyclic AMP Response Element Desire for food Diabetes Mellitus Dimensions Diurnal Rhythm Eating Equilibrium Exposure to Feedback Feeding behaviors Food Genetic Genetic Transcription Genomics Glucose Goals Grant Health High Fat Diet Homeostasis Hormones Human Hunger Hyperphagia Hypothalamic structure Impairment Insulin Light Link Metabolic syndrome Metabolism Midbrain structure Modernization Molecular Molecular Conformation Motivation Mus Neurons Obesity Obesity Epidemic Periodicity Peripheral Physiological Physiology Prosencephalon Public Health RNA Processing Regulation Rewards Role Site Sleep Sleep Wake Cycle Sleep disturbances Societies Testing Time Variant Ventral Tegmental Area Work blood glucose regulation circadian circadian pacemaker circadian regulation dopaminergic neuron energy balance feeding gene network glucose metabolism glucose tolerance hedonic impaired glucose tolerance innovation insight insulin secretion islet molecular clock obesity prevention shift work three dimensional structure transcription factor transcriptomics

项目摘要

PROJECT SUMMARY Circadian rhythms are autonomous cycles of behavior and physiology that undergo routine disruption in modern society due to the rise in shift work, exposure to blue light at night, disrupted sleep, and consumption of highly- palatable high-fat diet. Molecular clocks are encoded by transcription feedback loops that drive the 24-hr sleep- wake cycle and physiological rhythms in hormone levels, glucose metabolism, and energetics. In the previous grant period, we revealed an essential function for both brain and peripheral clocks in rhythmic energy homeostasis and glucose metabolism. We showed that morning/evening variation in chromatin conformation controls -cell insulin secretion. We also showed that clock ablation in neurons of forebrain and midbrain impairs appetitive drive, sleep/wake rhythms, energy balance, glucose tolerance, and transcription, although a gap remains in our understanding of the mechanisms underlying rhythmic integration of behavior and metabolism. Here we seek to extend our insight into circadian mechanisms linking behavior and metabolism. (i) In our first aim, we will dissect the cell and molecular basis for genomic rhythms driving -cell function important in glucose constancy across the sleep-wake cycle. (ii) In our second aim, we will identify the neurocircuit basis for rhythms of hedonic and homeostatic feeding coordinating appetitive drive with glucose homeostasis. An innovation of our work is the multidimensional integration of genetics, genomics, and behavioral analyses to gain molecular insight into rhythmic -cell function and neuronal control of hunger. Ultimately, we are poised to uncover new insight into how central and peripheral clocks impact physiology, findings which have broad implications for the treatment and prevention of obesity and metabolic syndrome.

项目总结