Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses.
Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases.
Department of Physiology, Faculty of Medicine, University of Helsinki, Finland.
Vilma
V
Aho
Department of Physiology, Faculty of Medicine, University of Helsinki, Finland.|Genomics and Biomarkers unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland.|Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Finland.|Stanford University Center for Sleep Sciences, Palo Alto, CA, USA.
Hanna M
HM
Ollila
Department of Chronic Disease Prevention, Population Studies Unit, National Institute for Health and Welfare, Turku, Finland.
Erkki
E
Kronholm
VTT Technical Research Centre of Finland, Espoo, Finland.|Steno Diabetes Center A/S, Gentofte, Denmark.
Isabel
I
Bondia-Pons
Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Pasi
P
Soininen
Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.
Antti J
AJ
Kangas
VTT Technical Research Centre of Finland, Espoo, Finland.
Mika
M
Hilvo
Department of Clinical Chemistry, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.
Ilkka
I
Seppälä
Genomics and Biomarkers unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland.|Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Johannes
J
Kettunen
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Mervi
M
Oikonen
Department of Clinical Chemistry, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.
Emma
E
Raitoharju
VTT Technical Research Centre of Finland, Espoo, Finland.|Steno Diabetes Center A/S, Gentofte, Denmark.
Tuulia
T
Hyötyläinen
Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Mika
M
Kähönen
Department of Medicine, University of Turku, and Division of Medicine, Turku University Hospital, Turku, Finland.
Jorma S A
JS
Viikari
Brain and Work Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland.
Mikko
M
Härmä
Brain and Work Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland.|Agora Center, University of Jyväskylä, Jyväskylä, Finland.
Mikael
M
Sallinen
Minerva Foundation Institute for Medical Research, Helsinki, Finland.|Institute of Biomedicine, Anatomy, University of Helsinki, Finland.
Vesa M
VM
Olkkonen
Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
Harri
H
Alenius
Genomics and Biomarkers unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland.
Matti
M
Jauhiainen
Genomics and Biomarkers unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland.|Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Finland.
Tiina
T
Paunio
Department of Clinical Chemistry, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.
Terho
T
Lehtimäki
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Veikko
V
Salomaa
VTT Technical Research Centre of Finland, Espoo, Finland.|Steno Diabetes Center A/S, Gentofte, Denmark.
Matej
M
Orešič
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Olli T
OT
Raitakari
Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|Oulu University Hospital, Oulu, Finland.|Computational Medicine, School of Social and Community Medicine &Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Mika
M
Ala-Korpela
Department of Physiology, Faculty of Medicine, University of Helsinki, Finland.
Tarja
T
Porkka-Heiskanen
D000328:Adult; D000368:Aged; D001774:Blood Chemical Analysis; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D005387:Finland; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000503:physiopathology*; D008297:Male; D008659:Metabolic Diseases / Q000453:epidemiology / Q000503:physiopathology*; D055442:Metabolome; D008875:Middle Aged; D012892:Sleep Deprivation / Q000150:complications*
D002784:Cholesterol