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Nat Commun. 2018 Sep 6;9(1):3622. doi: 10.1038/s41467-018-05933-8.

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

Author information

1
Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931, Köln, Germany.
2
Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), Joseph-Stelzmann-Str. 26, 50931, Köln, Germany.
3
Department of Laboratory Medicine, Medical University of Vienna, 1090, Vienna, Austria.
4
Department for Biochemistry and Molecular Biology (BMB), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
5
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelstrasse 20, 52074, Aachen, Germany.
6
Institute for Biochemistry and Molecular Cell Biology, Martinistraße 52, 20246, Hamburg, Germany.
7
Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195, Berlin, Germany.
8
Institute for Molecular Biology and Genetics, Aarhus University, C F Møllers Alle 3, 8000, Aarhus C, Denmark.
9
Department of Medicine, University of Leipzig, 04103, Leipzig, Germany.
10
Department of Laboratory Medicine, Medical University of Vienna, 1090, Vienna, Austria. martin.bilban@meduniwien.ac.at.
11
Core Facilities, Medical University of Vienna, 1090, Vienna, Austria. martin.bilban@meduniwien.ac.at.
12
Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931, Köln, Germany. janwilhelmkornfeld@bmb.sdu.dk.
13
Cologne Cluster of Excellence: Cellular Stress Responses in Ageing-associated Diseases (CECAD), Joseph-Stelzmann-Str. 26, 50931, Köln, Germany. janwilhelmkornfeld@bmb.sdu.dk.
14
Department for Biochemistry and Molecular Biology (BMB), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark. janwilhelmkornfeld@bmb.sdu.dk.

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.

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