Project Summary & Abstract The timing of energy intake relative to the light-dark and sleep-wake cycle plays an important role in the development of metabolic diseases. Consuming energy at an inappropriate time of day results in desynchrony of anabolic and catabolic processes that are regulated across the day by circadian clock systems. When mice are fed a high fat diet ad libitum, they eat throughout the day and night and become obese, but strikingly when the same diet is restricted to a short window at the appropriate circadian time (i.e., time-restricted feeding; TRF), they are protected against obesity. Little is known in humans regarding the influence of meal timing on whole body metabolism and the mechanisms involved. The overarching research goal of the present K01 Career Development Award is to leverage the pre-clinical evidence on the TRF paradigm to understand how meal timing affects fuel metabolism, metabolic flexibility, and the circadian landscape in humans. The proposed research plan serves as a vehicle to advance the applicant, Dr. Corey Rynders, PhD to independent investigator status over a period of five years of NIH-NIDDK K01 support. Dr. Wendy Kohrt at the University of Colorado – Anschutz Medical Campus and a multidisciplinary group of scientists with expertise in circadian physiology and metabolism (Drs. Wright, Bessesen, and Melanson) will oversee the training plan of Dr. Rynders and ensure his successful transition to an independent translational researcher. To achieve these aims, Dr. Rynders will need to gain new knowledge of circadian physiology, establish important collaborations in the circadian field, mature his expertise in metabolic research, and have protected time to acquire preliminary data to submit a competitive R01 application. The overall career goal is to develop an independent research program focused on how lifestyle factors impact the circadian regulation of metabolism in human participants. Study Design: The study will determine the effects of timed feeding on substrate metabolism, metabolic flexibility, and circadian rhythms measured in plasma and adipose tissue. Overweight adults (N=24) will undergo three 8-10d protocols (7d free-living; 1-3d inpatient) during which sleep timing remains consistent and energy-balanced meals are scheduled at- (a) 0.5h, 8h, and 15.5h after wake (prolonged feeding window); (b) 0.5h, 4h, and 8h after wake (early TRF); and (c) 8h, 12h, and 15.5h after wake (late TRF). Aim 1 will utilize stable isotope tracers and room calorimetry to test whether TRF increases dietary fat oxidation, 24h whole body fat oxidation, and the metabolic flexibility to fasting. Aim 2 will use continuous glucose monitoring and serial blood draws to determine whether TRF decreases 24h and postprandial glucose and insulin concentrations. Aim 3 will obtain fundamental data on whether meal timing and feeding duration results in phase shifts and/or amplitude changes in markers of the central clock (melat...