Peroxisomal β-oxidation acts as a sensor ...
Type de document :
Compte-rendu et recension critique d'ouvrage
PMID :
Titre :
Peroxisomal β-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis
Auteur(s) :
Ding, Lianggong [Auteur]
Sun, Wenfei [Auteur]
Balaz, Miroslav [Auteur]
Slovak Academy of Sciences [SAS]
Comenius University in Bratislava
He, Anyuan [Auteur]
Washington University School of Medicine in St. Louis
Anhui University [Hefei]
Klug, Manuel [Auteur]
Wieland, Stefan [Auteur]
Université de Bâle = University of Basel = Basel Universität [Unibas]
Caiazzo, Robert [Auteur]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Raverdy, Violeta [Auteur]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Pattou, Francois [Auteur]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Lefebvre, Philippe [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Lodhi, Irfan [Auteur]
Washington University School of Medicine in St. Louis
Staels, Bart [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Heim, Markus [Auteur]
Université de Bâle = University of Basel = Basel Universität [Unibas]
Wolfrum, Christian [Auteur correspondant]
Sun, Wenfei [Auteur]
Balaz, Miroslav [Auteur]
Slovak Academy of Sciences [SAS]
Comenius University in Bratislava
He, Anyuan [Auteur]
Washington University School of Medicine in St. Louis
Anhui University [Hefei]
Klug, Manuel [Auteur]
Wieland, Stefan [Auteur]
Université de Bâle = University of Basel = Basel Universität [Unibas]
Caiazzo, Robert [Auteur]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Raverdy, Violeta [Auteur]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Pattou, Francois [Auteur]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Lefebvre, Philippe [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Lodhi, Irfan [Auteur]
Washington University School of Medicine in St. Louis
Staels, Bart [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Heim, Markus [Auteur]
Université de Bâle = University of Basel = Basel Universität [Unibas]
Wolfrum, Christian [Auteur correspondant]
Titre de la revue :
Nature Metabolism
Pagination :
1648-1661
Éditeur :
Nature Publishing Group
Date de publication :
2021-12
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
To liberate fatty acids (FA) from intracellular stores, lipolysis is driven by the activity of the lipases ATGL, HSL and MGL. Excessive FA release as a result of uncontrolled lipolysis causes lipotoxicity, which can cause ...
Lire la suite >To liberate fatty acids (FA) from intracellular stores, lipolysis is driven by the activity of the lipases ATGL, HSL and MGL. Excessive FA release as a result of uncontrolled lipolysis causes lipotoxicity, which can cause metabolic disorders. However, whether cells can sense FA directly to regulate their levels to maintain cellular homeostasis is unknown. Here we report a sensing mechanism for cellular FA content, based on peroxisomal degradation of FA and coupled ROS production, which in turn regulates FA release by modulating lipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGL levels through post-translational ubiquitination. We demonstrate the importance of this pathway for NAFLD progression using genetic and pharmacological approaches to alter ROS levels, in vivo, which can be utilized to increase hepatic ATGL levels and ameliorate hepatic steatosis. The discovery of this peroxisomal β-oxidation mediated feedback mechanism, which is conserved in multiple organs, couples the functions of peroxisomes and lipid droplets and might serve as a new way to manipulate lipolysis to treat metabolic disorders.Lire moins >
Lire la suite >To liberate fatty acids (FA) from intracellular stores, lipolysis is driven by the activity of the lipases ATGL, HSL and MGL. Excessive FA release as a result of uncontrolled lipolysis causes lipotoxicity, which can cause metabolic disorders. However, whether cells can sense FA directly to regulate their levels to maintain cellular homeostasis is unknown. Here we report a sensing mechanism for cellular FA content, based on peroxisomal degradation of FA and coupled ROS production, which in turn regulates FA release by modulating lipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGL levels through post-translational ubiquitination. We demonstrate the importance of this pathway for NAFLD progression using genetic and pharmacological approaches to alter ROS levels, in vivo, which can be utilized to increase hepatic ATGL levels and ameliorate hepatic steatosis. The discovery of this peroxisomal β-oxidation mediated feedback mechanism, which is conserved in multiple organs, couples the functions of peroxisomes and lipid droplets and might serve as a new way to manipulate lipolysis to treat metabolic disorders.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Projet ANR :
Source :
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