Sleep loss disrupts morning-to-evening differences in human white adipose tissue transcriptome.

Sleep loss disrupts morning-to-evening differences in human white adipose tissue transcriptome.

J Clin Endocrinol Metab. 2018 Dec 06;:

Authors: Wilms B, Leineweber EM, Mölle M, Chamorro R, Pommerenke C, Salinas-Riester G, Sina C, Lehnert H, Oster H, Schmid SM

Abstract
Context: Chronodisruption as caused by e.g. perturbations of 24h-rhythms of physiology and behavior clearly 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 18-30years (mean±SEM: 24.0±0.9years) were studied. In randomized, balanced order they underwent three separate nights with regular sleep duration (8h sleep between 2300-0700h), sleep restriction (4h sleep between 0300-0700h), and sleep deprivation (SD; no sleep at all). Sleep was polysomnographically evaluated. WAT biopsy samples were taken twice at 2100h and 0700h to assess morning-to-evening-differences. WAT transcriptome profile was assessed by RNA-sequencing and expression of relevant circadian core clock genes analyzed. Glucose homeostasis, lipid profile and adipokines were assessed.
Results: Sleep restriction dramatically blunted morning-to-evening transcriptome variations with further dampening after SD. While most core clock genes remained stably rhythmic, morning-to-evening regulated pathways of carbohydrate and lipid metabolism were highly sensitive to sleep loss. Especially genes associated with carbohydrate breakdown lost rhythmicity after SD with an overall trend towards an up-regulation in the morning. In line with specific transcriptional changes in WAT, retinol-binding-protein 4 was increased and ß-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 in order to prevent metabolic disorders like obesity and type 2 diabetes.

PMID: 30535338 [PubMed - as supplied by publisher]

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