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 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.

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Publication Details

Journal
Nature Communications
Published
2024-11-28
DOI
https://doi.org/10.1038/s41467-024-54224-y
Citations
11
Primary Topic
Caveolin-1 and cellular processes
Type
article
Field-Weighted Citation Impact
3.59
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article

Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability

Dácil M. Pavón, Daniel Jiménez‐Carretero, Miguel Sánchez‐Álvarez, María C. M. Aboy-Pardal et al.
11 citations
Nature Communications
Caveolin-1 and cellular processes
3.59
article

Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability

Dácil M. Pavón, Daniel Jiménez‐Carretero, Miguel Sánchez‐Álvarez, María C. M. Aboy-Pardal, Carlos R. Guerrero, Rubén Nogueiras, Sara Terrés-Domínguez, Mauro Català-Montoro, Miguel Á. del Pozo, Ricardo Garcı́a, Cintia Folgueira, Víctor Jiménez-Jiménez, Guadalupe Sabio, Moreno Zamai, Fidel‐Nicolás Lolo, Ana Cerezo, Asier Echarri, Marta C. Guadamillas, Mónica Toledano-Donado
article en
11 citations

Abstract

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.

Nature CommunicationsVol. 15(1)
Catholic University of Ávila (ES), Universidad de Alcalá (ES), Spanish National Centre for Cardiovascular Research (ES), Spanish National Cancer Research Centre (ES), Instituto de Investigaciones Biomédicas Sols-Morreale (ES), Centro Nacional de Epidemiología (ES), Center for Research in Molecular Medicine and Chronic Diseases (ES), Instituto de Ciencia de Materiales de Madrid (ES), Eli Lilly (Spain) (ES), Spanish National Centre for Cardiovascular Research (ES), Centro de Investigaciones Biológicas Margarita Salas (ES), University of Castilla-La Mancha (ES)
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Caveolin-1 and cellular processes
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