Abstract

Context: Chronodisruption, as caused by such conditions as perturbations of 24-hour rhythms of physiology and behavior, may promote the development of metabolic diseases. Objective: To assess the acute effects of sleep curtailment on circadian regulation (i.e., morning-to-evening differences) of white adipose tissue (WAT) transcriptome in normal-weight men. Design: Fifteen healthy men aged 18 to 30 years (mean +/- SEM, 24.0 +/- 0.9years) were studied. In randomized, balanced order they underwent three separate nights with regular sleep duration (8 hours of sleep between 11: 00 PM and 7: 00 AM), sleep restriction (4 hours of sleep between 3: 00 AM and 7: 00 AM), and sleep deprivation (no sleep at all). Sleep was polysomnographically evaluated. WAT biopsy samples were taken twice at 9: 00 PM and 7: 00 AM to assess morning-to-evening differences. WAT transcriptome profile was assessed by RNA sequencing, and expression of relevant circadian core clock genes were analyzed. Glucose homeostasis, lipid profile, and adipokines were assessed. Results: Sleep restriction dramatically blunted morning-to-evening transcriptome variations with further dampening after sleep deprivation. Although most core clock genes remained stably rhythmic, morning-to-evening regulated pathways of carbohydrate and lipid metabolism were highly sensitive to sleep loss. In particular, genes associated with carbohydrate breakdown lost rhythmicity after sleep deprivation, with an overall trend toward an upregulation in the morning. In line with specific transcriptional changes in WAT, retinol-binding-protein 4 was increased and beta-cell secretory capacity was diminished. Conclusions: Acute sleep loss induces a profound restructuring of morning-to-evening WAT transcriptome with uncoupling from the local clock machinery, resulting in increased WAT carbohydrate turnover and impaired glucose homeostasis. Our data support an optimization of sleep duration and timing to prevent metabolic disorders such as obesity and type 2 diabetes.