PROJECT SUMMARY & ABSTRACT Does what time of day you exercise matter for weight loss? The objective of this proposal is to determine the effect of an equivalent dose of morning versus evening aerobic exercise on change in body weight, energy intake (EI), and components of energy expenditure (EE) in adults with overweight or obesity. Nearly two-thirds of US adults who attempt to lose weight engage in exercise as a strategy for weight loss. However, weight loss from exercise alone is often substantially less than predicted based on the calories burned in exercise. This is due to compensatory changes that occur in response to exercise (e.g. increases in EI and decreases in non-exercise EE) that limit the energy deficit produced by exercise. Thus, strategies that reduce the compensatory response could enhance the weight loss efficacy of exercise. Preliminary data suggests that morning exercise may limit development of compensation and thus be superior to evening exercise for weight loss. In a secondary data analysis of a 10-month supervised exercise intervention in adults with overweight or obesity, individuals who predominantly exercised in the morning exhibited three-fold greater weight loss compared to individuals who predominantly exercised in the evening, despite equivalent exercise EE and adherence. Further, 81% of morning exercisers achieved ≥5% weight loss, compared to 36% of evening exercisers. There was also evidence of differences in compensation. Despite no intervention on diet, morning exercisers decreased EI across the intervention, while evening exercisers increased EI. Morning exercisers increased total daily energy expenditure (TDEE) proportionately to the EE of exercise, while evening exercisers demonstrated attenuated increases in TDEE. However, these results were from a retrospective analysis in which participants were categorized by the time of day in which they predominantly performed exercise sessions. A rigorously designed randomized trial is needed to confirm these novel findings. In the proposed study, adults with overweight or obesity will be randomized to 7 months of supervised aerobic exercise (2000 kcal/week) performed either in the morning or the evening, and then followed for an additional 6 months. The central hypothesis is that morning exercise will result in greater weight loss as compared to evening exercise due to attenuated development of compensatory changes in EI and EE. The study will compare the effects of morning versus evening exercise on changes in body weight and body composition (Aim 1), changes in EI and appetite (Aim 2), changes in EE, non-exercise physical activity, and sedentary time (Aim 3), and changes in meal timing and sleep (Exploratory Aim 4). The approach is rigorous and innovative as exercise will be prescribed based on EE using indirect calorimetry, free- living TDEE and EI will be measured objectively (doubly-labeled water), and 24-hr patterns of physical activity, sedentary time, meal timi...