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LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat

Author

Listed:
  • Elena Schmidt

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Ines Dhaouadi

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Isabella Gaziano

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Matteo Oliverio

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Paul Klemm

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Motoharu Awazawa

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Gerfried Mitterer

    (Medical University of Vienna)

  • Eduardo Fernandez-Rebollo

    (University of Southern Denmark
    RWTH Aachen University Medical School)

  • Marta Pradas-Juni

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD)
    University of Southern Denmark)

  • Wolfgang Wagner

    (RWTH Aachen University Medical School)

  • Philipp Hammerschmidt

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Rute Loureiro

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD)
    University of Southern Denmark)

  • Christoph Kiefer

    (University of Southern Denmark)

  • Nils R. Hansmeier

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Sajjad Khani

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Matteo Bergami

    (Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Markus Heine

    (Institute for Biochemistry and Molecular Cell Biology)

  • Evgenia Ntini

    (Max Planck Institute for Molecular Genetics)

  • Peter Frommolt

    (Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Peter Zentis

    (Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD))

  • Ulf Andersson Ørom

    (Aarhus University)

  • Jörg Heeren

    (Institute for Biochemistry and Molecular Cell Biology)

  • Matthias Blüher

    (University of Leipzig)

  • Martin Bilban

    (Medical University of Vienna
    Medical University of Vienna)

  • Jan-Wilhelm Kornfeld

    (Max Planck Institute for Metabolism Research
    Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD)
    University of Southern Denmark)

Abstract

Increasing brown adipose tissue (BAT) thermogenesis in mice and humans improves metabolic health and understanding BAT function is of interest for novel approaches to counteract obesity. The role of long noncoding RNAs (lncRNAs) in these processes remains elusive. We observed maternally expressed, imprinted lncRNA H19 increased upon cold-activation and decreased in obesity in BAT. Inverse correlations of H19 with BMI were also observed in humans. H19 overexpression promoted, while silencing of H19 impaired adipogenesis, oxidative metabolism and mitochondrial respiration in brown but not white adipocytes. In vivo, H19 overexpression protected against DIO, improved insulin sensitivity and mitochondrial biogenesis, whereas fat H19 loss sensitized towards HFD weight gains. Strikingly, paternally expressed genes (PEG) were largely absent from BAT and we demonstrated that H19 recruits PEG-inactivating H19-MBD1 complexes and acts as BAT-selective PEG gatekeeper. This has implications for our understanding how monoallelic gene expression affects metabolism in rodents and, potentially, humans.

Suggested Citation

  • Elena Schmidt & Ines Dhaouadi & Isabella Gaziano & Matteo Oliverio & Paul Klemm & Motoharu Awazawa & Gerfried Mitterer & Eduardo Fernandez-Rebollo & Marta Pradas-Juni & Wolfgang Wagner & Philipp Hamme, 2018. "LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05933-8
    DOI: 10.1038/s41467-018-05933-8
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    Cited by:

    1. Adinarayana Marada & Corvin Walter & Tamara Suhm & Sahana Shankar & Arpita Nandy & Tilman Brummer & Ines Dhaouadi & F.-Nora Vögtle & Chris Meisinger, 2024. "DYRK1A signalling synchronizes the mitochondrial import pathways for metabolic rewiring," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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