Human Resting Energy Expenditure Varies with Circadian Phase

There is emerging evidence that circadian misalignment may alter energy expenditure, leading to obesity risk among those with irregular schedules [1-5]. It has been reported that energy expenditure is affected by the timing of sleep, exercise, and meals [6]. However, it is unclear whether the circadian system also modulates energy expenditure, independent of behavioral state and food intake. Here, we used a forced desynchrony protocol to examine whether fasted resting energy expenditure (REE) varies with circadian phase in seven participants. This protocol allowed us to uncouple sleep-wake and activity-related effects from the endogenous circadian rhythm, demonstrating that REE varies by circadian phase. REE is lowest at circadian phase similar to 0 degrees, corresponding to the endogenous core body temperature (CBT) nadir in the late biological night, and highest at circadian phase similar to 180 degrees in the biological afternoon and evening. Furthermore, we found that respiratory quotient (RQ), reflecting macronutrient utilization, also varies by circadian phase. RQ is lowest at circadian phase similar to 240 degrees and highest at circadian phase similar to 60 degrees, which corresponds to biological morning. This is the first characterization of a circadian profile in fasted resting energy expenditure and fasted respiratory quotient (with rhythmic profiles in both carbohydrate and lipid oxidation), decoupled from effects of activity, sleep-wake cycle, and diet in humans. The rhythm in energy expenditure and macronutrient metabolism may contribute to greater weight gain in shift workers and others with irregular schedules.