miRNAs in human subcutaneous adipose tissue: Effects of weight loss induced by hypocaloric diet and exercise

Authors

  • Malene M. Kristensen,

    Corresponding author
    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Peter K. Davidsen,

    1. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Andreas Vigelsø,

    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Christina N. Hansen,

    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Lars J. Jensen,

    1. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Niels Jessen,

    1. Department of Biomedicine, Aarhus University, Aarhus, Denmark
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  • Jens M. Bruun,

    1. Randers Regional Hospital, Medical Department M, Randers, Denmark
    2. Department of Nutrition, Exercise, and Sports (NEXS), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Flemming Dela,

    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    2. Department of Geriatrics, Bispebjerg University Hospital, Copenhagen, Denmark
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  • Jørn W. Helge

    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Funding agencies: We gratefully acknowledge Konsul J.Fogh-Nielsens legat, the Danish Medical Research Council (22-02-0527), the NORDEA Foundation, the Novo Nordisk Foundation (NNF14CC0001), and Torben og Alice Frimodts Fond for funding this work.

  • Disclosure: The authors declared no conflict of interest.

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

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