Metabolic and neuroendocrine adaptability following one night of partial sleep restriction in Dutch males - Nederlandse Vereniging voor Endocrinologie

Introduction Chronic and acute short sleep associate with many adverse effects. Metabolic and neuroendocrine effects during the day following short sleep, however, are unknown. Methods Randomized cross-over study using short sleep (4h) vs normal sleep (8h) in 31 males (31 years (IQR 23-47, BMI 26.0±4.2 kg/m² (20.1-35.0). Glucose, lipid, incretin, ACTH and cortisol levels, as well as respiratory exchange ratio (RER; indirect calorimetry) were assessed following standardized mixed meals. RNAseq of morning skeletal muscle biopsies and pathway analysis on differentially expressed genes was performed. Results Short sleep increased fasting free fatty acids (0.34 mmol/L (IQR 0.26–0.38) vs 0.47 mmol/L (IQR 0.38–0.70), P<0.0001). Cortisol peaked upon early wake-up, which eliminated a peak at normal wake-up. Morning postprandial glucose peaked later (time P<0.001, levels P=0.106, pattern P=0.031), whilst insulin was unaffected. Afternoon postprandial insulin was lowered (time P<0.001, levels P=0.044, pattern P=0.419), whilst glucose was unaffected. Morning and afternoon postprandial TC, and LDL-c were lowered (morning: TC, time P<0.0001, levels P=0.009, pattern P=0.289; LDL-c, time P<0.001, levels P=0.038, pattern P=0.797; afternoon: TC, time P<0.001, levels P=0.007, pattern P=0.92; LDL-c, time P<0.001, levels P=0.055, pattern P=0.991). Pathway analysis of muscle revealed increased fatty acid oxidation (FAO), reflected by increased Oxidative Phosphorylation and Mitochondrial Dysfunction pathways, accompanied by lowered fasting RER (0.87 (IQR 0.86–0.92) vs 0.86 (IQR 0.84–0.87), P=0.0033). Conclusions Acute partial sleep restriction subtly and temporarily changed glucose dynamics (morning), and insulin levels (afternoon), and lowered TC and LDL-c levels in the morning and afternoon, with concurrent increased FAO and mitochondrial dysfunction pathways in skeletal muscle, and calorimetric shifting from glucose towards lipid oxidation (fasted and postprandial), potentially highlighting increased delipidation of chylomicrons following sleep restriction.