Cargando…
Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet
The synthesis of fatty acids from acetyl–coenzyme A (AcCoA) is deregulated in diverse pathologies, including cancer. Here, we report that fatty acid accumulation is negatively regulated by nucleoside diphosphate kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that w...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482350/ https://www.ncbi.nlm.nih.gov/pubmed/37672589 http://dx.doi.org/10.1126/sciadv.adh0140 |
_version_ | 1785102154824941568 |
---|---|
author | Iuso, Domenico Garcia-Saez, Isabel Couté, Yohann Yamaryo-Botté, Yoshiki Boeri Erba, Elisabetta Adrait, Annie Zeaiter, Nour Tokarska-Schlattner, Malgorzata Jilkova, Zuzana Macek Boussouar, Fayçal Barral, Sophie Signor, Luca Couturier, Karine Hajmirza, Azadeh Chuffart, Florent Bourova-Flin, Ekaterina Vitte, Anne-Laure Bargier, Lisa Puthier, Denis Decaens, Thomas Rousseaux, Sophie Botté, Cyrille Schlattner, Uwe Petosa, Carlo Khochbin, Saadi |
author_facet | Iuso, Domenico Garcia-Saez, Isabel Couté, Yohann Yamaryo-Botté, Yoshiki Boeri Erba, Elisabetta Adrait, Annie Zeaiter, Nour Tokarska-Schlattner, Malgorzata Jilkova, Zuzana Macek Boussouar, Fayçal Barral, Sophie Signor, Luca Couturier, Karine Hajmirza, Azadeh Chuffart, Florent Bourova-Flin, Ekaterina Vitte, Anne-Laure Bargier, Lisa Puthier, Denis Decaens, Thomas Rousseaux, Sophie Botté, Cyrille Schlattner, Uwe Petosa, Carlo Khochbin, Saadi |
author_sort | Iuso, Domenico |
collection | PubMed |
description | The synthesis of fatty acids from acetyl–coenzyme A (AcCoA) is deregulated in diverse pathologies, including cancer. Here, we report that fatty acid accumulation is negatively regulated by nucleoside diphosphate kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that were recently found to bind CoA. We show that NME1 additionally binds AcCoA and that ligand recognition involves a unique binding mode dependent on the CoA/AcCoA 3′ phosphate. We report that Nme2 knockout mice fed a high-fat diet (HFD) exhibit excessive triglyceride synthesis and liver steatosis. In liver cells, NME2 mediates a gene transcriptional response to HFD leading to the repression of fatty acid accumulation and activation of a protective gene expression program via targeted histone acetylation. Our findings implicate NME1/2 in the epigenetic regulation of a protective liver response to HFD and suggest a potential role in controlling AcCoA usage between the competing paths of histone acetylation and fatty acid synthesis. |
format | Online Article Text |
id | pubmed-10482350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-104823502023-09-07 Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet Iuso, Domenico Garcia-Saez, Isabel Couté, Yohann Yamaryo-Botté, Yoshiki Boeri Erba, Elisabetta Adrait, Annie Zeaiter, Nour Tokarska-Schlattner, Malgorzata Jilkova, Zuzana Macek Boussouar, Fayçal Barral, Sophie Signor, Luca Couturier, Karine Hajmirza, Azadeh Chuffart, Florent Bourova-Flin, Ekaterina Vitte, Anne-Laure Bargier, Lisa Puthier, Denis Decaens, Thomas Rousseaux, Sophie Botté, Cyrille Schlattner, Uwe Petosa, Carlo Khochbin, Saadi Sci Adv Biomedicine and Life Sciences The synthesis of fatty acids from acetyl–coenzyme A (AcCoA) is deregulated in diverse pathologies, including cancer. Here, we report that fatty acid accumulation is negatively regulated by nucleoside diphosphate kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that were recently found to bind CoA. We show that NME1 additionally binds AcCoA and that ligand recognition involves a unique binding mode dependent on the CoA/AcCoA 3′ phosphate. We report that Nme2 knockout mice fed a high-fat diet (HFD) exhibit excessive triglyceride synthesis and liver steatosis. In liver cells, NME2 mediates a gene transcriptional response to HFD leading to the repression of fatty acid accumulation and activation of a protective gene expression program via targeted histone acetylation. Our findings implicate NME1/2 in the epigenetic regulation of a protective liver response to HFD and suggest a potential role in controlling AcCoA usage between the competing paths of histone acetylation and fatty acid synthesis. American Association for the Advancement of Science 2023-09-06 /pmc/articles/PMC10482350/ /pubmed/37672589 http://dx.doi.org/10.1126/sciadv.adh0140 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Iuso, Domenico Garcia-Saez, Isabel Couté, Yohann Yamaryo-Botté, Yoshiki Boeri Erba, Elisabetta Adrait, Annie Zeaiter, Nour Tokarska-Schlattner, Malgorzata Jilkova, Zuzana Macek Boussouar, Fayçal Barral, Sophie Signor, Luca Couturier, Karine Hajmirza, Azadeh Chuffart, Florent Bourova-Flin, Ekaterina Vitte, Anne-Laure Bargier, Lisa Puthier, Denis Decaens, Thomas Rousseaux, Sophie Botté, Cyrille Schlattner, Uwe Petosa, Carlo Khochbin, Saadi Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet |
title | Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet |
title_full | Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet |
title_fullStr | Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet |
title_full_unstemmed | Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet |
title_short | Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet |
title_sort | nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482350/ https://www.ncbi.nlm.nih.gov/pubmed/37672589 http://dx.doi.org/10.1126/sciadv.adh0140 |
work_keys_str_mv | AT iusodomenico nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT garciasaezisabel nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT couteyohann nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT yamaryobotteyoshiki nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT boerierbaelisabetta nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT adraitannie nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT zeaiternour nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT tokarskaschlattnermalgorzata nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT jilkovazuzanamacek nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT boussouarfaycal nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT barralsophie nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT signorluca nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT couturierkarine nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT hajmirzaazadeh nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT chuffartflorent nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT bourovaflinekaterina nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT vitteannelaure nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT bargierlisa nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT puthierdenis nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT decaensthomas nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT rousseauxsophie nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT bottecyrille nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT schlattneruwe nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT petosacarlo nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet AT khochbinsaadi nucleosidediphosphatekinases1and2regulateaprotectiveliverresponsetoahighfatdiet |