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

Elena Schmidt, Ines Dhaouadi, Isabella Gaziano, Matteo Oliverio, Paul Klemm, Motoharu Awazawa, Gerfried Mitterer, Eduardo Fernandez-Rebollo, Marta Pradas-Juni, Wolfgang Wagner, Philipp Hammerschmidt, Rute Loureiro, Christoph Kiefer, Nils R. Hansmeier, Sajjad Khani, Matteo Bergami, Markus Heine, Evgenia Ntini, Peter Frommolt, Peter Zentis, Ulf Andersson Ørom, Jörg Heeren, Matthias Blüher, Martin Bilban () and Jan-Wilhelm Kornfeld ()
Additional contact information
Elena Schmidt: Max Planck Institute for Metabolism Research
Ines Dhaouadi: Max Planck Institute for Metabolism Research
Isabella Gaziano: Max Planck Institute for Metabolism Research
Matteo Oliverio: Max Planck Institute for Metabolism Research
Paul Klemm: Max Planck Institute for Metabolism Research
Motoharu Awazawa: Max Planck Institute for Metabolism Research
Gerfried Mitterer: Medical University of Vienna
Eduardo Fernandez-Rebollo: University of Southern Denmark
Marta Pradas-Juni: Max Planck Institute for Metabolism Research
Wolfgang Wagner: RWTH Aachen University Medical School
Philipp Hammerschmidt: Max Planck Institute for Metabolism Research
Rute Loureiro: Max Planck Institute for Metabolism Research
Christoph Kiefer: University of Southern Denmark
Nils R. Hansmeier: Max Planck Institute for Metabolism Research
Sajjad Khani: Max Planck Institute for Metabolism Research
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
Jan-Wilhelm Kornfeld: Max Planck Institute for Metabolism Research

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05933-8

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DOI: 10.1038/s41467-018-05933-8

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