Daily Rhythms and Health: Obesity and Related Disorders

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 (but 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.