Abstract

Background: Circadian misalignment (CM), the mismatch between timing of behaviors and internal body clock, increases cardiometabolic risk, but the mechanisms are not fully understood. Population studies in night shift workers and intervention studies attempting to replicate CM have often been confounded by differences in energy intake, sleep duration and timing, and eating window duration. We aimed to investigate the effects of CM, induced by delaying mealtimes relative to wake time, independent of sleep timing and duration as well as duration of eating window, on energy expenditure (EE) and substrate oxidation. We hypothesized that CM would reduce EE and increase respiratory quotient (RQ) relative to meals closer to wake time (circadian alignment [CA]). Methods: We used a 2-phase, randomized, crossover study. Men and women (age 20-49 y) were studied under controlled feeding conditions (CA and CM). Each phase included a 10-h eating window at 0900-1900 h (CA) or 1300-2300 h (CM) with fixed mealtimes. Bedtimes were set at 2400-0800 h. Minute-by-minute EE, RQ, and substrate oxidation were obtained over 23 h in a metabolic chamber on d 3-4 and 14-15. Post-meal EE, RQ, and substrate oxidation were calculated as the average of 2-h, 1-h, and 30 min data collections following breakfast, dinner, and snack, respectively. Data were analyzed using a linear mixed effects model including condition, day, and day-by-condition interaction as main predictor variables, and phase as an adjusting covariate. As an exploratory aim, sex-by-condition interaction was also included in the model. Results: Three men and 4 women completed both study phases (age 37.6±8.8 y, BMI 30.8±3.2 kg/m 2 ). EE did not differ between CM and CA. Post-meal RQ for breakfast (p=0.06), dinner (p<0.001), and snack (p<0.001) were higher in CM vs CA. Glucose oxidation after dinner (p<0.001) and snack (p<0.01) were higher in CM vs CA. There were sex-by-condition interactions on EE and glucose oxidation after breakfast (both p=0.06) and dinner (p<0.05), and on EE after snack (p<0.01). In general, CA resulted in greater rise in EE and lesser reduction in glucose oxidation following meals in men compared to women. Conclusion: Delaying mealtimes by 4 h, independent of sleep duration, timing, or diet composition, shifts nutrient metabolism towards greater carbohydrate and lower fat oxidation. Sex may influence the effect of CM on energy metabolism and should be considered in investigations of cardiometabolic risk associated with shift work and late-night eating.

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