Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability

Adipocytes expand massively to accommodate excess energy stores and protect the organism from lipotoxicity. Adipose tissue expandability is at the center of disorders such as obesity and lipodystrophy; however, little is known about the relevance of adipocyte biomechanics on the etiology of these co...

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Autores: Aboy-Pardal , Maria C M, Guadamillas Mora, Marta Carmen, Guerrero , Carlos R, Catala Montoro , Mauro, Toledano-Donado , Mónica, Terrés Domínguez, Sara, Pavón , Dácil M, Jiménez Jiménez, Víctor, Jiménez Carretero, Daniel, Zamai , Moreno, Folgueira , Cintia, Cerezo , Ana, Lolo , Fidel-Nicolas, Nogueiras , Rubén, Sabio , Guadalupe, Sánchez Álvarez, Miguel, Echarri , Asier, García , Ricardo, del Pozo , Miguel A
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/46322
Acceso en línea:https://doi.org/10.1038/s41467-024-54224-y
https://hdl.handle.net/10578/46322
Access Level:acceso abierto
Palabra clave:Adipocytes
Caveolae
Lipid droplet
Mechanical adaptability
Obesity
Phosphoregulation
Plasma membrane
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spelling Plasma membrane remodeling determines adipocyte expansion and mechanical adaptabilityAboy-Pardal , Maria C MGuadamillas Mora, Marta CarmenGuerrero , Carlos RCatala Montoro , MauroToledano-Donado , MónicaTerrés Domínguez, SaraPavón , Dácil MJiménez Jiménez, VíctorJiménez Carretero, DanielZamai , MorenoFolgueira , CintiaCerezo , AnaLolo , Fidel-NicolasNogueiras , RubénSabio , GuadalupeSánchez Álvarez, MiguelEcharri , AsierGarcía , Ricardodel Pozo , Miguel AAdipocytesCaveolaeLipid dropletMechanical adaptabilityObesityPhosphoregulationPlasma membraneAdipocytes expand massively to accommodate excess energy stores and protect the organism from lipotoxicity. Adipose tissue expandability is at the center of disorders such as obesity and lipodystrophy; however, little is known about the relevance of adipocyte biomechanics on the etiology of these conditions. Here, we show in male mice in vivo that the adipocyte plasma membrane undergoes caveolar domain reorganization upon lipid droplet expansion. As the lipid droplet grows, caveolae disassemble to release their membrane reservoir and increase cell surface area, and transfer specific caveolar components to the LD surface. Adipose tissue null for caveolae is stiffer, shows compromised deformability, and is prone to rupture under mechanical compression. Mechanistically, phosphoacceptor Cav1 Tyr14 is required for caveolae disassembly: adipocytes bearing a Tyr14Phe mutation at this residue are stiffer and smaller, leading to decreased adiposity in vivo; exhibit deficient transfer of Cav1 and EHD2 to the LD surface, and show distinct Cav1 molecular dynamics and tension adaptation. These results indicate that Cav1 phosphoregulation modulates caveolar dynamics as a relevant component of the homeostatic mechanoadaptation of the differentiated adipocyte.NATURE PUBLISHING GROUP202620262024info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://doi.org/10.1038/s41467-024-54224-yhttps://hdl.handle.net/10578/46322reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésSAF2017-83130-RMINSEV 1512-07-2016BFU2016-81912-REDCPID2020-118658RB-I00Tec4Bio-CM, S2018/NMT¬4443201936-30-31PROYE20089DELPHR20-00075BIOPOL, 641639RYC2020-029690)PID2021−128106NA-I00MINECO-PID2019-104399RB-I00MCIN/AEI/10.13039/501100011033CEX2020-001041-SCEX2020-001041-Sinfo:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/463222026-05-27T07:36:41Z
dc.title.none.fl_str_mv Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
title Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
spellingShingle Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
Aboy-Pardal , Maria C M
Adipocytes
Caveolae
Lipid droplet
Mechanical adaptability
Obesity
Phosphoregulation
Plasma membrane
title_short Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
title_full Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
title_fullStr Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
title_full_unstemmed Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
title_sort Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
dc.creator.none.fl_str_mv Aboy-Pardal , Maria C M
Guadamillas Mora, Marta Carmen
Guerrero , Carlos R
Catala Montoro , Mauro
Toledano-Donado , Mónica
Terrés Domínguez, Sara
Pavón , Dácil M
Jiménez Jiménez, Víctor
Jiménez Carretero, Daniel
Zamai , Moreno
Folgueira , Cintia
Cerezo , Ana
Lolo , Fidel-Nicolas
Nogueiras , Rubén
Sabio , Guadalupe
Sánchez Álvarez, Miguel
Echarri , Asier
García , Ricardo
del Pozo , Miguel A
author Aboy-Pardal , Maria C M
author_facet Aboy-Pardal , Maria C M
Guadamillas Mora, Marta Carmen
Guerrero , Carlos R
Catala Montoro , Mauro
Toledano-Donado , Mónica
Terrés Domínguez, Sara
Pavón , Dácil M
Jiménez Jiménez, Víctor
Jiménez Carretero, Daniel
Zamai , Moreno
Folgueira , Cintia
Cerezo , Ana
Lolo , Fidel-Nicolas
Nogueiras , Rubén
Sabio , Guadalupe
Sánchez Álvarez, Miguel
Echarri , Asier
García , Ricardo
del Pozo , Miguel A
author_role author
author2 Guadamillas Mora, Marta Carmen
Guerrero , Carlos R
Catala Montoro , Mauro
Toledano-Donado , Mónica
Terrés Domínguez, Sara
Pavón , Dácil M
Jiménez Jiménez, Víctor
Jiménez Carretero, Daniel
Zamai , Moreno
Folgueira , Cintia
Cerezo , Ana
Lolo , Fidel-Nicolas
Nogueiras , Rubén
Sabio , Guadalupe
Sánchez Álvarez, Miguel
Echarri , Asier
García , Ricardo
del Pozo , Miguel A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Adipocytes
Caveolae
Lipid droplet
Mechanical adaptability
Obesity
Phosphoregulation
Plasma membrane
topic Adipocytes
Caveolae
Lipid droplet
Mechanical adaptability
Obesity
Phosphoregulation
Plasma membrane
description Adipocytes expand massively to accommodate excess energy stores and protect the organism from lipotoxicity. Adipose tissue expandability is at the center of disorders such as obesity and lipodystrophy; however, little is known about the relevance of adipocyte biomechanics on the etiology of these conditions. Here, we show in male mice in vivo that the adipocyte plasma membrane undergoes caveolar domain reorganization upon lipid droplet expansion. As the lipid droplet grows, caveolae disassemble to release their membrane reservoir and increase cell surface area, and transfer specific caveolar components to the LD surface. Adipose tissue null for caveolae is stiffer, shows compromised deformability, and is prone to rupture under mechanical compression. Mechanistically, phosphoacceptor Cav1 Tyr14 is required for caveolae disassembly: adipocytes bearing a Tyr14Phe mutation at this residue are stiffer and smaller, leading to decreased adiposity in vivo; exhibit deficient transfer of Cav1 and EHD2 to the LD surface, and show distinct Cav1 molecular dynamics and tension adaptation. These results indicate that Cav1 phosphoregulation modulates caveolar dynamics as a relevant component of the homeostatic mechanoadaptation of the differentiated adipocyte.
publishDate 2024
dc.date.none.fl_str_mv 2024
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://doi.org/10.1038/s41467-024-54224-y
https://hdl.handle.net/10578/46322
url https://doi.org/10.1038/s41467-024-54224-y
https://hdl.handle.net/10578/46322
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv SAF2017-83130-R
MINSEV 1512-07-2016
BFU2016-81912-REDC
PID2020-118658RB-I00
Tec4Bio-CM, S2018/NMT¬4443
201936-30-31
PROYE20089DELP
HR20-00075
BIOPOL, 641639
RYC2020-029690)
PID2021−128106NA-I00
MINECO-PID2019-104399RB-I00
MCIN/AEI/10.13039/501100011033
CEX2020-001041-S
CEX2020-001041-S
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv NATURE PUBLISHING GROUP
publisher.none.fl_str_mv NATURE PUBLISHING GROUP
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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