A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
29 05 2023
Historique:
received: 24 09 2021
accepted: 11 05 2023
medline: 31 5 2023
pubmed: 30 5 2023
entrez: 29 5 2023
Statut: epublish

Résumé

In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.

Identifiants

pubmed: 37248239
doi: 10.1038/s41467-023-38663-7
pii: 10.1038/s41467-023-38663-7
pmc: PMC10226981
doi:

Substances chimiques

Ferritins 9007-73-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3092

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2023. The Author(s).

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Auteurs

Julian Petersen (J)

Department of Orthodontics, University Leipzig Medical Center, Leipzig, Germany. julian.petersen@medizin.uni-leipzig.de.

Lukas Englmaier (L)

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, 1090, Vienna, Austria.

Artem V Artemov (AV)

Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Irina Poverennaya (I)

Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Ruba Mahmoud (R)

Department of Orthodontics, University Leipzig Medical Center, Leipzig, Germany.

Thibault Bouderlique (T)

Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Marketa Tesarova (M)

Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.

Ruslan Deviatiiarov (R)

Regulatory Genomics Research Center, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Endocrinology Research Center, Moscow, Russia.

Anett Szilvásy-Szabó (A)

Laboratory of Integrative Neuroendocrinology, Institute of Experimental Medicine, 1083, Budapest, Hungary.

Evgeny E Akkuratov (EE)

Department of Applied Physics, Royal Institute of Technology, Science for Life Laboratory, 171 65, Stockholm, Sweden.
University of Oxford, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford, OX3 9DS, UK.

David Pajuelo Reguera (D)

Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics, Vestec, Czech Republic.

Hugo Zeberg (H)

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Marketa Kaucka (M)

Max Planck Institute for Evolutionary Biology, Plön, 24306, Germany.

Maria Eleni Kastriti (ME)

Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Jan Krivanek (J)

Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Tomasz Radaszkiewicz (T)

Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.

Kristína Gömöryová (K)

Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.

Sarah Knauth (S)

Department of Orthodontics, University Leipzig Medical Center, Leipzig, Germany.

David Potesil (D)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

Zbynek Zdrahal (Z)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

Ranjani Sri Ganji (RS)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

Anna Grabowski (A)

Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Miriam E Buhl (ME)

Institute of Pathology & Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, Germany.

Tomas Zikmund (T)

Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.

Michaela Kavkova (M)

Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Håkan Axelson (H)

Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, Scheelevägen 2, Lund, Sweden.

David Lindgren (D)

Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, Scheelevägen 2, Lund, Sweden.

Rafael Kramann (R)

Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.

Christoph Kuppe (C)

Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany.

Ferenc Erdélyi (F)

Medical Gene Technology Unit, Institute of Experimental Medicine, Budapest, Hungary.

Zoltán Máté (Z)

Medical Gene Technology Unit, Institute of Experimental Medicine, Budapest, Hungary.

Gábor Szabó (G)

Medical Gene Technology Unit, Institute of Experimental Medicine, Budapest, Hungary.

Till Koehne (T)

Department of Orthodontics, University Leipzig Medical Center, Leipzig, Germany.

Tibor Harkany (T)

Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Kaj Fried (K)

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Jozef Kaiser (J)

Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.

Peter Boor (P)

Institute of Pathology & Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, Germany.

Csaba Fekete (C)

Laboratory of Integrative Neuroendocrinology, Institute of Experimental Medicine, 1083, Budapest, Hungary.

Jan Rozman (J)

Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics, Vestec, Czech Republic.
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6, avenue du Swing, 4367, Belvaux, Luxembourg.

Petr Kasparek (P)

Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics, Vestec, Czech Republic.

Jan Prochazka (J)

Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics, Vestec, Czech Republic.

Radislav Sedlacek (R)

Institute of Molecular Genetics of the Czech Academy of Science, Czech Centre for Phenogenomics, Vestec, Czech Republic.

Vitezslav Bryja (V)

Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.

Oleg Gusev (O)

Regulatory Genomics Research Center, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Igor Adameyko (I)

Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria. igor.adameyko@meduniwien.ac.at.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. igor.adameyko@meduniwien.ac.at.

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