Daily Rhythms and Health: Obesity and Related Disorders

描述(申请人提供)：这项提案的目标是促进我发展成为一名独立的调查者和教育者，专注于阐明日常节律中断导致肥胖的机制。对啮齿动物和人类的研究表明，肥胖个体的进食时间会发生变化，但关于这种表型如何影响肥胖的病理生理学，人们知之甚少。为了研究节律代谢过程的调节以及它们在饮食诱导的肥胖中是如何改变的，我开发了一个急性模型来监测喂食高脂饮食一周的小鼠的进食行为和组织节律。我的初步研究表明，在摄入富含饱和脂肪的高脂肪饮食时，日常饮食行为的节奏会立即改变，肝脏生物钟的时间也会显著提前。这项拟议的研究旨在阐明高脂肪饮食改变饮食行为和肝脏生理的机制。在这项建议中，进食行为的实时成像和肝脏生物发光节律的监测将被用来检验这样的假设，即食用富含饱和脂肪(bt不是单不饱和脂肪)的饮食通过Toll样受体4介导的机制改变每日的摄食行为和肝脏生理节律。为了实现这项建议的目标，我将把我在昼夜生物学方面的经验与新陈代谢生理学分析的新技术结合起来。我将利用我的合作导师和指导委员会的长处，以及我以前接受的培训，培养一条独立的、新颖的研究路线。我职业发展计划的关键要素包括新陈代谢生理学的教学课程，沉浸在新陈代谢和昼夜生物学研究丰富的知识环境中，以及通过正式的研讨会、研讨会以及与初级和高级科学家的互动获得职业发展技能。通过汇集一支才华横溢的指导团队、拥有最先进设备和设施的协同研究环境以及职业成功培训，这个职业发展奖将使我能够实现我的长期职业目标，即成为一名成功的独立科学家，其研究广泛影响人类健康。

DESCRIPTION (provided by applicant): The goal of this proposal is to foster my development into an independent investigator and educator focused on elucidating the mechanisms by which disruption of daily rhythms contributes to obesity. Studies in rodents and humans have demonstrated that the timing of food intake is altered in obese individuals, but little is known about how this phenotype contributes to the pathophysiology of obesity. To investigate the tuning of rhythmic metabolic processes and how they are altered in diet-induced obesity, I developed an acute model to monitor eating behavior and tissue rhythms in mice fed high-fat diet for one week. My preliminary studies demonstrate that the daily rhythm of eating behavior is immediately altered and the timing of the circadian clock in the liver is robustly advanced during consumption of high-fat diet rich in saturated fat. The proposed studies aim to elucidate the mechanism whereby consumption of high-fat diet alters eating behavior and liver physiology. In this proposal, real-time imaging of eating behavior and monitoring of liver bioluminescence rhythms will be utilized to test the hypothesis that consumption of a diet rich in saturated fat (bt not monounsaturated fat) alters daily rhythms of feeding behavior and liver physiology through a toll-like receptor 4-mediated mechanism. To achieve the goals of this proposal, I will combine my experience in circadian biology with new techniques assaying metabolic physiology. I will draw from the strengths of my co-mentors and mentoring committee and from my prior training to cultivate an independent and novel line of research. Key elements of my career development plan include didactic coursework in metabolic physiology, immersion in an intellectual environment rich in the study of metabolism and circadian biology, and acquisition of career development skills through formal seminars, workshops, and interactions with junior and senior scientists. By bringing together a talented mentoring team, a synergistic research environment with state-of-the-art equipment and facilities, and training in career success, this career development award will allow me to achieve my long-term career goal of becoming a successful independent scientist whose research broadly impacts human health.