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...

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Autores: Sabate-Perez, A, Romero, M, Sanchez-Fernandez-de-Landa, P, Carobbio, S, Mouratidis, M, Sala, D, Engel, P, Villena, JA, Virtue, S, Vidal-Puig, A, Palacin, M, Testar, X, Zorzano, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Centro de Investigación Principe Felipe (CIPF)
Repositorio:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
OAI Identifier:oai:cipf.fundanetsuite.com:p3955
Acceso en línea:https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3955
Access Level:acceso abierto
Palabra clave:Autophagy
brown adipose tissue
metabolism
obesity
thermogenesis
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spelling Autophagy-mediated NCOR1 degradation is required for brown fat maturation and thermogenesisSabate-Perez, ARomero, MSanchez-Fernandez-de-Landa, PCarobbio, SMouratidis, MSala, DEngel, PVillena, JAVirtue, SVidal-Puig, APalacin, MTestar, XZorzano, AAutophagybrown adipose tissuemetabolismobesitythermogenesisBrown 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.TAYLOR & FRANCIS INC2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3955AutophagyISSN: 15548627ISSNe: 15548635reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)instname:Centro de Investigación Principe Felipe (CIPF)Inglésinfo:eu-repo/semantics/openAccessoai:cipf.fundanetsuite.com:p39552026-06-17T11:19:47Z
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
Sabate-Perez, A
Autophagy
brown adipose tissue
metabolism
obesity
thermogenesis
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 Sabate-Perez, A
Romero, M
Sanchez-Fernandez-de-Landa, P
Carobbio, S
Mouratidis, M
Sala, D
Engel, P
Villena, JA
Virtue, S
Vidal-Puig, A
Palacin, M
Testar, X
Zorzano, A
author Sabate-Perez, A
author_facet Sabate-Perez, A
Romero, M
Sanchez-Fernandez-de-Landa, P
Carobbio, S
Mouratidis, M
Sala, D
Engel, P
Villena, JA
Virtue, S
Vidal-Puig, A
Palacin, M
Testar, X
Zorzano, A
author_role author
author2 Romero, M
Sanchez-Fernandez-de-Landa, P
Carobbio, S
Mouratidis, M
Sala, D
Engel, P
Villena, JA
Virtue, S
Vidal-Puig, A
Palacin, M
Testar, X
Zorzano, A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autophagy
brown adipose tissue
metabolism
obesity
thermogenesis
topic Autophagy
brown adipose tissue
metabolism
obesity
thermogenesis
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 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3955
url https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3955
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv TAYLOR & FRANCIS INC
publisher.none.fl_str_mv TAYLOR & FRANCIS INC
dc.source.none.fl_str_mv Autophagy
ISSN: 15548627
ISSNe: 15548635
reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
instname:Centro de Investigación Principe Felipe (CIPF)
instname_str Centro de Investigación Principe Felipe (CIPF)
reponame_str r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
collection r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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