A Central Circadian Clock-Adipose Tissue Circuit Regulates Thermogenesis and Energy Balance

中央昼夜节律时钟-脂肪组织回路调节产热和能量平衡

• 批准号: 10373115
• 负责人: Chelsea Hepler
• 金额: $ 6.98万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373115
• 关键词: Adipocytes; Adipose tissue; Adult; Automobile Driving; Body Weight decreased; Brain; Brown Fat; Circadian Dysregulation; Circadian Rhythms; Darkness; Data; Development; Diet; Diurnal Rhythm; Energy Intake; Energy Metabolism; Fasting; Genetic; Glucose Intolerance; Goals; Health; High Fat Diet; Homeostasis; Hour; House mice; Human; Individual; Insulin Resistance; Intermittent fasting; Jet Lag Syndrome; Lead; Light; Link; Lipolysis; Mediating; Metabolic; Metabolic Diseases; Metabolic syndrome; Metabolism; Mus; Mutant Strains Mice; Neurons; Obesity; Play; Reporter; Role; Sleep; Sleep Disorders; Stimulus; Testing; Thermogenesis; Time; Time-restricted feeding; Tissues; Weight; Weight Gain; Wild Type Mouse; circadian; circadian pacemaker; energy balance; experience; experimental study; feeding; food consumption; glycemic control; improved; molecular clock; neuromechanism; nodal myocyte; novel; novel therapeutic intervention; obesity development; programs; shift work; suprachiasmatic nucleus

PROJECT SUMMARY Disruption of circadian rhythms is strongly correlated to obesity and metabolic diseases. Mice with a dysfunctional clock and individuals who experience shift work, jet lag, and sleep disorders develop glucose intolerance, insulin resistance, and weight gain. Recent data indicates the timing of food consumption is a key determinant of metabolic health. Mice and humans in constant darkness have a disrupted diurnal rhythm of diet-induced thermogenesis (DIT). Furthermore, our lab has found that isocaloric feeding in mice during the light period results in pronounced weight gain and glucose intolerance, as compared to the dark period. This effect of differential weight gain during the light vs dark period is lost in mice lacking adipose tissue thermogenesis. This suggests adipose tissue thermogenesis is regulated in a circadian manner to align DIT with optimal feeding times (dark period in mice). However, the mechanisms that integrate adipose tissue thermogenesis with feeding remain unclear. In this proposal, we aim to characterize the central circadian control of adipose tissue sympathetic stimulation and thermogenic activation. The experiments in this proposal will reveal a novel neurocircuit that aligns feeding rhythms with adipose tissue DIT to maintain energy homeostasis.

项目总结