Z Gastroenterol 2019; 57(01): e53-e54
DOI: 10.1055/s-0038-1677189
3. Metabolism (incl. NAFLD)
Georg Thieme Verlag KG Stuttgart · New York

The RNA binding protein HuR is a master regulator of hepatic-lipid homeostasis

P Subramanian
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
,
M Grzybek
2   Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
3   German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
,
A Palladini
2   Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
3   German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
,
A Sinha
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
,
S Gargani
4   Aristotle University of Thessaloniki, School of Biology, Department of Genetics, Development & Molecular Biology, Thessaloniki, Greece
5   Biomedical Sciences Research Centre 'Alexander Fleming', Division of Immunology, Vari, Greece
,
I Mitroulis
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
,
M Lesche
6   Deep Sequencing Group, Biotechnology Center, Technische Universität Dresden, Dresden, Germany
,
R Burkhardt
7   Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Germany
9   LIFE – Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany
,
M Brosch
8   Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
,
N Techritz
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
,
A Witt
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
,
KJ Chung
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
,
M Nati
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
,
A Dahl
6   Deep Sequencing Group, Biotechnology Center, Technische Universität Dresden, Dresden, Germany
,
P Mirtschink
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
,
N Zamboni
10   Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
,
Ü Coskun
2   Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
3   German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
,
J Hampe
8   Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
,
D Kontoyiannis
4   Aristotle University of Thessaloniki, School of Biology, Department of Genetics, Development & Molecular Biology, Thessaloniki, Greece
5   Biomedical Sciences Research Centre 'Alexander Fleming', Division of Immunology, Vari, Greece
,
T Chavakis
1   Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

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RNA binding proteins (RBP) play an essential role in the post-transcriptional control of RNAs. Less is known about the role of RBPs in the liver, particularly the hepatocyte-specific function. The RBP, HuR (encoded by Elavl1; embryonic lethal abnormal vision like 1) regulates mRNA splicing and stability. We found that HuR is diminished in human livers with steatosis and/or non-alcoholic steatohepatitis (NASH) and that it regulates a network of pathways that are essential in hepatic-lipid homeostasis maintenance. Hepatocyte-specific HuR deficient mice exhibited severe steatosis of the liver already at steady state, as compared to their wild type littermates. This phenotype was further enhanced in a model of diet-induced NASH, whereby HuR deficiency promoted inflammation and fibrosis development. Lipidomic analysis revealed that, HuR deficient livers at steady state accumulated a triglyceride-signature resembling that of NASH-livers of HuR sufficient mice. Moreover, hepatocyte-protective bile acid species were reduced, whereas, proinflammatory lipid mediators such as leukotrienes were induced in the absence of HuR, as studied by metabolomics. By studying HuR-RNA interactions in the liver, we found that HuR binds to targets involved in various lipid metabolic processes and that it prevents the hepatic-accumulation of adverse lipid species. The current study emphasizes how post-transcriptional processes control lipid metabolism to maintain homeostasis in the liver.