miRNAs in human subcutaneous adipose tissue: Effects of weight loss induced by hypocaloric diet and exercise.
Obesity is central in the development of insulin resistance. However, the underlying mechanisms still need elucidation. Dysregulated microRNAs (miRNAs; post-transcriptional regulators) in adipose tissue may present an important link.



The miRNA expression in subcutaneous adipose tissue from 19 individuals with severe obesity (10 women and 9 men) before and after a 15-week weight loss intervention was studied using genome-wide microarray analysis. The microarray results were validated with RT-qPCR, and pathway enrichment analysis of in silico predicted targets was performed to elucidate the biological consequences of the miRNA dysregulation. Lastly, the messenger RNA (mRNA) and/or protein expression of multiple predicted targets as well as several proteins involved in lipolysis were investigated.



The intervention led to upregulation of miR-29a-3p and miR-29a-5p and downregulation of miR-20b-5p. The mRNA and protein expression of predicted targets was not significantly affected by the intervention. However, negative correlations between miR-20b-5p and the protein levels of its predicted target, acyl-CoA synthetase long-chain family member 1, were observed. Several other miRNA-target relationships correlated negatively, indicating possible miRNA regulation, including miR-29a-3p and lipoprotein lipase mRNA levels. Proteins involved in lipolysis were not affected by the intervention.



Weight loss influenced several miRNAs, some of which were negatively correlated with predicted targets. These dysregulated miRNAs may affect adipocytokine signaling and forkhead box protein O signaling.
Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Malene M
0000-0003-2716-1034
MM
Kristensen
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Peter K
PK
Davidsen
Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Andreas
A
Vigelsø
Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Christina N
CN
Hansen
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Lars J
LJ
Jensen
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Niels
N
Jessen
Randers Regional Hospital, Medical Department M, Randers, Denmark.|Department of Nutrition, Exercise, and Sports (NEXS), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens M
JM
Bruun
Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Geriatrics, Bispebjerg University Hospital, Copenhagen, Denmark.
Flemming
F
Dela
Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jørn W
JW
Helge
D000328:Adult; D004038:Diet, Reducing; D015536:Down-Regulation; D015444:Exercise; D005247:Feeding Behavior; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D050151:Subcutaneous Fat / Q000378:metabolism*; D016896:Treatment Outcome; D015431:Weight Loss / Q000502:physiology*
D035683:MicroRNAs