title: A single night of sleep curtailment increases plasma acylcarnitines: Novel insights in the relationship between sleep and insulin resistance.
abstract: We have previously shown that acute sleep curtailment induces insulin resistance, both in healthy individuals as well as in patients with type 1 diabetes, suggesting a causal role for sleep disturbances in pathogenesis of insulin resistance, independent of endogenous insulin production. However, the underlying mechanisms remain unclear. This study aimed to explore the metabolic pathways affected by sleep loss using targeted metabolomics in human fasting plasma samples. Healthy individuals (n = 9) and patients with type 1 diabetes (n = 7) were studied after a single night of short sleep (4 h) versus normal sleep (8 h) in a cross-over design. Strikingly, one night of short sleep specifically increased the plasma levels of acylcarnitines, essential intermediates in mitochondrial fatty acid oxidation (FAO). Specifically, short sleep increased plasma levels of tetradecenoyl-l-carnitine (C14:1) (+32%, p = 2.67*10(-4)), octadecanoyl-l-carnitine (C18:1) (+22%, p = 1.92*10(-4)) and octadecadienyl-l-carnitine (C18:2) (+27%, p = 1.32*10(-4)). Since increased plasma acylcarnitine levels could be a sign of disturbed FAO, it is possible that sleep curtailment acutely induces inefficient mitochondrial function. Our observations provide a basis for further research into the role of acylcarnitines as a potential mechanistic pathway by which sleep deprivation - even short term - causes adverse metabolic effects, such as insulin resistance.
authors.affiliation: Dept. of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: R.van_den_Berg.ENDO@lumc.nl.
authors.forename: Rosa
authors.initials: R
authors.lastname: van den Berg
authors.affiliation: Dept. of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Dept. of Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Epidemiology Section, Dept. of BESC, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Mook-Kanamori
authors.affiliation: Dept. of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Donga
authors.affiliation: Dept. of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: van Dijk
authors.affiliation: Dept. of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J Gert
authors.initials: JG
authors.lastname: van Dijk
authors.affiliation: Dept. of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Lammers
authors.affiliation: Dept. of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Klaas W
authors.initials: KW
authors.lastname: van Kralingen
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany; Lehrstul für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Dept. of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.affiliation: Dept. of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Dept. Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
authors.affiliation: Dept. of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eleonora P M
authors.initials: EP
authors.lastname: Corssmit
authors.affiliation: Dept. of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.affiliation: Dept. of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
mesh_terms: D000328:Adult; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D055432:Metabolomics; D012890:Sleep
chemical_list: C116917:acylcarnitine; D002331:Carnitine
keywords: Acylcarnitines; Diabetes; Insulin resistance; Metabolomics; Sleep deprivation; Sleep loss