• Open Access

MicroRNA-26 Family Is Required for Human Adipogenesis and Drives Characteristics of Brown Adipocytes

Authors

  • Michael Karbiener,

    Corresponding author
    1. RNA Biology Group, Institute for Genomics and Bioinformatics, Graz University of Technology, Austria
    • Correspondence: Marcel Scheideler, Ph.D., Graz University of Technology, Petersgasse 14/V, 8010 Graz, Austria. Telephone: 43-316-873-5334; Fax: 43-316-873105334; e-mail: marcel.scheideler@tugraz.at; or Michael Karbiener, Ph.D., Graz University of Technology, Petersgasse 14/V, 8010 Graz, Austria. Telephone: 43-316-873-5346; Fax: 43–316-873105346; e-mail: michael.karbiener@tugraz.at

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  • Didier F. Pisani,

    1. Université Nice Sophia Antipolis, iBV, Nice, France
    2. CNRS, iBV, Nice, France
    3. Inserm, iBV, Nice, France
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  • Andrea Frontini,

    1. Department of Experimental and Clinical Medicine, Obesity Center, United Hospitals-University of Ancona (Politecnica delle Marche), Ancona, Italy
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  • Lisa M. Oberreiter,

    1. RNA Biology Group, Institute for Genomics and Bioinformatics, Graz University of Technology, Austria
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  • Eleonore Lang,

    1. RNA Biology Group, Institute for Genomics and Bioinformatics, Graz University of Technology, Austria
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  • Alexandros Vegiopoulos,

    1. Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany
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  • Karin Mössenböck,

    1. Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany
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  • Gerwin A. Bernhardt,

    1. Department of Orthopedic Surgery, Medical University Graz, Graz, Austria
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  • Torsten Mayr,

    1. Institute of Analytical Chemistry and Food Chemistry, Graz University of Technology, Graz, Austria
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  • Florian Hildner,

    1. Red Cross Blood Transfusion Service of Upper Austria, Austrian Cluster for Tissue Regeneration, Linz, Austria
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  • Johannes Grillari,

    1. Department of Biotechnology, BOKU-VIBT University of Natural Resources and Life Sciences Vienna, Vienna, Austria
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  • Gérard Ailhaud,

    1. Université Nice Sophia Antipolis, iBV, Nice, France
    2. CNRS, iBV, Nice, France
    3. Inserm, iBV, Nice, France
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  • Stephan Herzig,

    1. Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany
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  • Saverio Cinti,

    1. Department of Experimental and Clinical Medicine, Obesity Center, United Hospitals-University of Ancona (Politecnica delle Marche), Ancona, Italy
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  • Ez-Zoubir Amri,

    1. Université Nice Sophia Antipolis, iBV, Nice, France
    2. CNRS, iBV, Nice, France
    3. Inserm, iBV, Nice, France
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  • Marcel Scheideler

    Corresponding author
    1. RNA Biology Group, Institute for Genomics and Bioinformatics, Graz University of Technology, Austria
    • Correspondence: Marcel Scheideler, Ph.D., Graz University of Technology, Petersgasse 14/V, 8010 Graz, Austria. Telephone: 43-316-873-5334; Fax: 43-316-873105334; e-mail: marcel.scheideler@tugraz.at; or Michael Karbiener, Ph.D., Graz University of Technology, Petersgasse 14/V, 8010 Graz, Austria. Telephone: 43-316-873-5346; Fax: 43–316-873105346; e-mail: michael.karbiener@tugraz.at

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Abstract

Adipose tissue contains thermogenic adipocytes (i.e., brown and brite/beige) that oxidize nutrients at exceptionally high rates via nonshivering thermogenesis. Its recent discovery in adult humans has opened up new avenues to fight obesity and related disorders such as diabetes. Here, we identified miR-26a and -26b as key regulators of human white and brite adipocyte differentiation. Both microRNAs are upregulated in early adipogenesis, and their inhibition prevented lipid accumulation while their overexpression accelerated it. Intriguingly, miR-26a significantly induced pathways related to energy dissipation, shifted mitochondrial morphology toward that seen in brown adipocytes, and promoted uncoupled respiration by markedly increasing the hallmark protein of brown fat, uncoupling protein 1. By combining in silico target prediction, transcriptomics, and an RNA interference screen, we identified the sheddase ADAM metallopeptidase domain 17 (ADAM17) as a direct target of miR-26 that mediated the observed effects on white and brite adipogenesis. These results point to a novel, critical role for the miR-26 family and its downstream effector ADAM17 in human adipocyte differentiation by promoting characteristics of energy-dissipating thermogenic adipocytes. Stem Cells 2014;32:1578–1590

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