Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome: the cardiovascular risk in Young Finns Study.
Since metabolic syndrome (MetS) is a collection of cardiovascular risk factors involving multiple signaling systems, we related the metabolic abnormalities associated with MetS with circulating microRNA profiles to pinpoint the affected signaling pathways. The blood microRNA profile, genome wide gene expression and serum NMR metabolomics were analyzed from 71 participants of the Young Finns Study. We found nine microRNAs that associated significantly with metabolites connected to MetS. MicroRNA-144-5p concentration correlated with glucose levels, hsa-1207-5p with glycosylated hemoglobin and hsa-miR-484 with metabolites related to insulin resistance. Hsa-miR-625-3p correlated with cholesterol levels, hsa-miR-1237-3p and hsa-miR-331-3p expression with certain fatty acids levels and hsa-miR-129-1-3p, -129-2-3p, and -1288-3p with glycerol levels. The down-regulated targets of miR-1207-5p and -129-2-3p were enriched in PI3K and MAPK pathways and 8 out of the 12 enriched pathways were down-regulated in individuals with MetS. In conclusion microRNAs associated with several aspects of MetS, possibly regulating glucose and lipid metabolism.
Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland. Electronic address: emma.raitoharju@uta.fi.
Emma
E
Raitoharju
Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
Ilkka
I
Seppälä
Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland; Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland.
Niku
N
Oksala
Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
Leo-Pekka
LP
Lyytikäinen
Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Turku University Central Hospital, Turku, Finland.
Olli
O
Raitakari
Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland.
Jorma
J
Viikari
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 and the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Mika
M
Ala-Korpela
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; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Antti J
AJ
Kangas
Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany.
Melanie
M
Waldenberger
Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
Norman
N
Klopp
Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
Thomas
T
Illig
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki and Turku, Finland.
Jaana
J
Leiviskä
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki and Turku, Finland.
Britt-Marie
BM
Loo
Department of Pediatrics, University of Tampere and Tampere University Hospital, Tampere, Finland.
Nina
N
Hutri-Kähönen
Department of Clinical Physiology, Tampere University Hospital, School of Medicine, University of Tampere, Tampere, Finland.
Mika
M
Kähönen
Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
Reijo
R
Laaksonen
Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
Terho
T
Lehtimäki
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005387:Finland; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006442:Glycated Hemoglobin / Q000378:metabolism; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications / Q000235:genetics; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D015398:Signal Transduction
D001786:Blood Glucose; D002784:Cholesterol; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D005990:Glycerol; D007328:Insulin; D035683:MicroRNAs
Diabetes; MRNA expression; Metabolic syndrome; MicroRNA; NMR metabolomics