• Hanne K J Gonnissen, Femke Rutters, Claire Mazuy, Eveline A P Martens, Tanja C Adam, and Margriet S Westerterp-Plantenga.
• Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, Netherlands. hkj.gonnissen@maastrichtuniversity.nl
• Am. J. Clin. Nutr. 2012 Oct 1;96(4):689-97.

BackgroundThe disruption of the circadian system has been associated with the development of obesity.ObjectiveWe examined the effects of circadian misalignment on sleep, energy expenditure, substrate oxidation, appetite, and related hormones.DesignThirteen subjects [aged 24.3 ± 2.5 (mean ± SD) y; BMI (in kg/m²): 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 × 21 h) and a phase delay (3 × 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.ResultsCircadian 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).ConclusionsThe 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.

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