Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis
Brown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a macroautophagic/autophagic-dependent mechanism of peroxisome proliferator-activated receptor gamma (PPARG) activity regulation that indu...
| Autores: | , , , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versión aceptada para publicación |
| Data de publicação: | 2022 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/201831 |
| Acesso em linha: | https://hdl.handle.net/2445/201831 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Metabolisme Obesitat Autofàgia Teixit adipós Metabolism Obesity Autophagy Adipose tissues |
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Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesisSabaté Pérez, AlbaRomero, MontserratSànchez Fernàndez de Landa, PaulaCarobbio, StefaniaMouratidis, MichailSala Cano, DavidEngel Rocamora, PabloVillena, Josep A.Virtue, SamVidal Puig, AntonioPalacín Prieto, ManuelTestar, XavierZorzano Olarte, AntonioMetabolismeObesitatAutofàgiaTeixit adipósMetabolismObesityAutophagyAdipose tissuesBrown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a macroautophagic/autophagic-dependent mechanism of peroxisome proliferator-activated receptor gamma (PPARG) activity regulation that induces brown adipose differentiation and thermogenesis and that is mediated by TP53INP2. Disruption of TP53INP2-dependent autophagy reduced brown adipogenesis in cultured cells. In vivo specific-tp53inp2 ablation in brown precursor cells or in adult mice decreased the expression of thermogenic and mature adipocyte genes in BAT. As a result, TP53INP2-deficient mice had reduced UCP1 content in BAT and impaired maximal thermogenic capacity, leading to lipid accumulation and to positive energy balance. Mechanistically, TP53INP2 stimulates PPARG activity and adipogenesis in brown adipose cells by promoting the autophagic degradation of NCOR1, a PPARG co-repressor. Moreover, the modulation of TP53INP2 expression in BAT and in human brown adipocytes suggests that this protein increases PPARG activity during metabolic activation of brown fat. In all, we have identified a novel molecular explanation for the contribution of autophagy to BAT energy metabolism that could facilitate the design of therapeutic strategies against obesity and its metabolic complications.Landes Bioscience2023202320222023info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion22 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/201831Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1080/15548627.2022.2111081Autophagy, 2022, vol. 19, num. 3, p. 904-925https://doi.org/10.1080/15548627.2022.2111081(c) Landes Bioscience , 2022info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2018312026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis |
| title |
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis |
| spellingShingle |
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis Sabaté Pérez, Alba Metabolisme Obesitat Autofàgia Teixit adipós Metabolism Obesity Autophagy Adipose tissues |
| title_short |
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis |
| title_full |
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis |
| title_fullStr |
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis |
| title_full_unstemmed |
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis |
| title_sort |
Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesis |
| dc.creator.none.fl_str_mv |
Sabaté Pérez, Alba Romero, Montserrat Sànchez Fernàndez de Landa, Paula Carobbio, Stefania Mouratidis, Michail Sala Cano, David Engel Rocamora, Pablo Villena, Josep A. Virtue, Sam Vidal Puig, Antonio Palacín Prieto, Manuel Testar, Xavier Zorzano Olarte, Antonio |
| author |
Sabaté Pérez, Alba |
| author_facet |
Sabaté Pérez, Alba Romero, Montserrat Sànchez Fernàndez de Landa, Paula Carobbio, Stefania Mouratidis, Michail Sala Cano, David Engel Rocamora, Pablo Villena, Josep A. Virtue, Sam Vidal Puig, Antonio Palacín Prieto, Manuel Testar, Xavier Zorzano Olarte, Antonio |
| author_role |
author |
| author2 |
Romero, Montserrat Sànchez Fernàndez de Landa, Paula Carobbio, Stefania Mouratidis, Michail Sala Cano, David Engel Rocamora, Pablo Villena, Josep A. Virtue, Sam Vidal Puig, Antonio Palacín Prieto, Manuel Testar, Xavier Zorzano Olarte, Antonio |
| author2_role |
author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Metabolisme Obesitat Autofàgia Teixit adipós Metabolism Obesity Autophagy Adipose tissues |
| topic |
Metabolisme Obesitat Autofàgia Teixit adipós Metabolism Obesity Autophagy Adipose tissues |
| description |
Brown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a macroautophagic/autophagic-dependent mechanism of peroxisome proliferator-activated receptor gamma (PPARG) activity regulation that induces brown adipose differentiation and thermogenesis and that is mediated by TP53INP2. Disruption of TP53INP2-dependent autophagy reduced brown adipogenesis in cultured cells. In vivo specific-tp53inp2 ablation in brown precursor cells or in adult mice decreased the expression of thermogenic and mature adipocyte genes in BAT. As a result, TP53INP2-deficient mice had reduced UCP1 content in BAT and impaired maximal thermogenic capacity, leading to lipid accumulation and to positive energy balance. Mechanistically, TP53INP2 stimulates PPARG activity and adipogenesis in brown adipose cells by promoting the autophagic degradation of NCOR1, a PPARG co-repressor. Moreover, the modulation of TP53INP2 expression in BAT and in human brown adipocytes suggests that this protein increases PPARG activity during metabolic activation of brown fat. In all, we have identified a novel molecular explanation for the contribution of autophagy to BAT energy metabolism that could facilitate the design of therapeutic strategies against obesity and its metabolic complications. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2023 2023 2023 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/201831 |
| url |
https://hdl.handle.net/2445/201831 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: https://doi.org/10.1080/15548627.2022.2111081 Autophagy, 2022, vol. 19, num. 3, p. 904-925 https://doi.org/10.1080/15548627.2022.2111081 |
| dc.rights.none.fl_str_mv |
(c) Landes Bioscience , 2022 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) Landes Bioscience , 2022 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
22 p. application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Landes Bioscience |
| publisher.none.fl_str_mv |
Landes Bioscience |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Bioquímica i Biomedicina Molecular) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| reponame_str |
Recercat. Dipósit de la Recerca de Catalunya |
| collection |
Recercat. Dipósit de la Recerca de Catalunya |
| repository.name.fl_str_mv |
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| repository.mail.fl_str_mv |
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1869425356217253888 |
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15,812429 |