Effect of a phase advance and phase delay of the 24-h cycle on energy metabolism, appetite, and related hormones

BACKGROUND: The disruption of the circadian system has been associated with the development of obesity. OBJECTIVE: We examined the effects of circadian misalignment on sleep, energy expenditure, substrate oxidation, appetite, and related hormones. DESIGN: Thirteen subjects [aged 24.3 +/- 2.5 (mean +/- SD) y; BMI (in kg/m(2)): 23.6 +/- 1.7 (mean +/- SD)] completed a randomized crossover study. For each condition, subjects stayed time blinded in the respiration chamber during 3 light-entrained circadian cycles that resulted in a phase advance (3 x 21 h) and a phase delay (3 x 27 h) compared with during a 24-h cycle. Sleep, energy expenditure, substrate oxidation, and appetite were quantified. Blood and saliva samples were taken to determine melatonin, glucose, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1), and cortisol concentrations. RESULTS: Circadian misalignment, either phase advanced or phase delayed, did not result in any changes in appetite or energy expenditure, whereas meal-related blood variables (glucose, insulin, ghrelin, leptin, and GLP-1) followed the new meal patterns. However, phase-advanced misalignment caused flattening of the cortisol-secretion pattern (P < 0.001), increased insulin concentrations (P = 0.04), and increased carbohydrate oxidation (P = 0.03) and decreased protein oxidation (P = 0.001). Phase-delayed misalignment increased rapid eye movement sleep (P < 0.001) and the sleeping metabolic rate (P = 0.02), increased glucose (P = 0.02) and decreased GLP-1 (P = 0.02) concentrations, and increased carbohydrate oxidation (P = 0.01) and decreased protein oxidation (P = 0.003). CONCLUSIONS: The main effect of circadian misalignment, either phase advanced or phase delayed, is a concomitant disturbance of the glucose-insulin metabolism and substrate oxidation, whereas the energy balance or sleep is not largely affected. Chronically eating and sleeping at unusual circadian times may create a health risk through a metabolic disturbance. This trial was registered at the International Clinical Trials Registry Platform (http://apps.who.int/trialsearch/) as NTR2926