IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40596-0.html
   My bibliography  Save this article

Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence

Author

Listed:
  • Aina Lluch

    (Institut d’Investigació Biomèdica de Girona (IDIBGI)
    Instituto de Salud Carlos III (ISCIII))

  • Jessica Latorre

    (Institut d’Investigació Biomèdica de Girona (IDIBGI)
    Instituto de Salud Carlos III (ISCIII))

  • Angela Serena-Maione

    (Centro Cardiologico Monzino IRCCS)

  • Isabel Espadas

    (University Pablo de Olavide)

  • Estefanía Caballano-Infantes

    (Institut d’Investigació Biomèdica de Girona (IDIBGI)
    Instituto de Salud Carlos III (ISCIII))

  • José M. Moreno-Navarrete

    (Institut d’Investigació Biomèdica de Girona (IDIBGI)
    Instituto de Salud Carlos III (ISCIII))

  • Núria Oliveras-Cañellas

    (Institut d’Investigació Biomèdica de Girona (IDIBGI)
    Instituto de Salud Carlos III (ISCIII))

  • Wifredo Ricart

    (Institut d’Investigació Biomèdica de Girona (IDIBGI)
    Instituto de Salud Carlos III (ISCIII))

  • María M. Malagón

    (Instituto de Salud Carlos III (ISCIII)
    University of Cordoba, Reina Sofia University Hospital)

  • Alejandro Martin-Montalvo

    (University Pablo de Olavide)

  • Walter Birchmeier

    (Max Delbrück Center for Molecular Medicine)

  • Witold Szymanski

    (Philipps University)

  • Johannes Graumann

    (Philipps University)

  • María Gómez-Serrano

    (Philipps University)

  • Elena Sommariva

    (Centro Cardiologico Monzino IRCCS)

  • José M. Fernández-Real

    (Institut d’Investigació Biomèdica de Girona (IDIBGI)
    Instituto de Salud Carlos III (ISCIII)
    University of Girona)

  • Francisco J. Ortega

    (Institut d’Investigació Biomèdica de Girona (IDIBGI)
    Instituto de Salud Carlos III (ISCIII))

Abstract

Plakophilin-2 (PKP2) is a key component of desmosomes, which, when defective, is known to promote the fibro-fatty infiltration of heart muscle. Less attention has been given to its role in adipose tissue. We report here that levels of PKP2 steadily increase during fat cell differentiation, and are compromised if adipocytes are exposed to a pro-inflammatory milieu. Accordingly, expression of PKP2 in subcutaneous adipose tissue diminishes in patients with obesity, and normalizes upon mild-to-intense weight loss. We further show defective PKP2 in adipocytes to break cell cycle dynamics and yield premature senescence, a key rheostat for stress-induced adipose tissue dysfunction. Conversely, restoring PKP2 in inflamed adipocytes rewires E2F signaling towards the re-activation of cell cycle and decreased senescence. Our findings connect the expression of PKP2 in fat cells to the physiopathology of obesity, as well as uncover a previously unknown defect in cell cycle and adipocyte senescence due to impaired PKP2.

Suggested Citation

  • Aina Lluch & Jessica Latorre & Angela Serena-Maione & Isabel Espadas & Estefanía Caballano-Infantes & José M. Moreno-Navarrete & Núria Oliveras-Cañellas & Wifredo Ricart & María M. Malagón & Alejandro, 2023. "Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40596-0
    DOI: 10.1038/s41467-023-40596-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40596-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40596-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Changsung Kim & Johnson Wong & Jianyan Wen & Shirong Wang & Cheng Wang & Sean Spiering & Natalia G. Kan & Sonia Forcales & Pier Lorenzo Puri & Teresa C. Leone & Joseph E. Marine & Hugh Calkins & Danie, 2013. "Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs," Nature, Nature, vol. 494(7435), pages 105-110, February.
    2. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Marina Cerrone & Jerome Montnach & Xianming Lin & Yan-Ting Zhao & Mingliang Zhang & Esperanza Agullo-Pascual & Alejandra Leo-Macias & Francisco J. Alvarado & Igor Dolgalev & Thomas V. Karathanos & Kab, 2017. "Plakophilin-2 is required for transcription of genes that control calcium cycling and cardiac rhythm," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    4. Margo P. Emont & Christopher Jacobs & Adam L. Essene & Deepti Pant & Danielle Tenen & Georgia Colleluori & Angelica Vincenzo & Anja M. Jørgensen & Hesam Dashti & Adam Stefek & Elizabeth McGonagle & So, 2022. "A single-cell atlas of human and mouse white adipose tissue," Nature, Nature, vol. 603(7903), pages 926-933, March.
    5. Birgit Gustafson & Annika Nerstedt & Ulf Smith, 2019. "Reduced subcutaneous adipogenesis in human hypertrophic obesity is linked to senescent precursor cells," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiangwei Li & Thomas Delerue & Ben Schöttker & Bernd Holleczek & Eva Grill & Annette Peters & Melanie Waldenberger & Barbara Thorand & Hermann Brenner, 2022. "Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Hao A. Duong & Kenkichi Baba & Jason P. DeBruyne & Alec J. Davidson & Christopher Ehlen & Michael Powell & Gianluca Tosini, 2024. "Environmental circadian disruption re-writes liver circadian proteomes," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Ramachandran Prakasam & Angela Bonadiman & Roberta Andreotti & Emanuela Zuccaro & Davide Dalfovo & Caterina Marchioretti & Debasmita Tripathy & Gianluca Petris & Eric N. Anderson & Alice Migazzi & Lau, 2023. "LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. Li Guo & Cheng Hu & Yang Liu & Xiaoyu Chen & Deli Song & Runling Shen & Zhanzhen Liu & Xudong Jia & Qinfen Zhang & Yuanzhu Gao & Zhezhi Deng & Tao Zuo & Jun Hu & Wenbo Zhu & Jing Cai & Guangmei Yan & , 2023. "Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Cecilia Pessoa Rodrigues & Aindrila Chatterjee & Meike Wiese & Thomas Stehle & Witold Szymanski & Maria Shvedunova & Asifa Akhtar, 2021. "Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    7. Tianshi Feng & Xuemei Zhao & Ping Gu & Wah Yang & Cunchuan Wang & Qingyu Guo & Qiaoyun Long & Qing Liu & Ying Cheng & Jin Li & Cynthia Kwan Yui Cheung & Donghai Wu & Xinyu Kong & Yong Xu & Dewei Ye & , 2022. "Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Chih-Hao Wang & Tadataka Tsuji & Li-Hong Wu & Cheng-Ying Yang & Tian Lian Huang & Mari Sato & Farnaz Shamsi & Yu-Hua Tseng, 2024. "Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Shuai Yan & Anna Santoro & Micah J. Niphakis & Antonio M. Pinto & Christopher L. Jacobs & Rasheed Ahmad & Radu M. Suciu & Bryan R. Fonslow & Rachel A. Herbst-Graham & Nhi Ngo & Cassandra L. Henry & Dy, 2024. "Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    10. Elisa Bellucci & Andrea Benazzo & Chunming Xu & Elena Bitocchi & Monica Rodriguez & Saleh Alseekh & Valerio Di Vittori & Tania Gioia & Kerstin Neumann & Gaia Cortinovis & Giulia Frascarelli & Ester Mu, 2023. "Selection and adaptive introgression guided the complex evolutionary history of the European common bean," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Jiayin Peng & Lili Han & Biao Liu & Jiawen Song & Yuang Wang & Kunpeng Wang & Qian Guo & XinYan Liu & Yu Li & Jujin Zhang & Wenqing Wu & Sheng Li & Xin Fu & Cheng-le Zhuang & Weikang Zhang & Shengbao , 2023. "Gli1 marks a sentinel muscle stem cell population for muscle regeneration," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Brent S. Perlman & Noah Burget & Yeqiao Zhou & Gregory W. Schwartz & Jelena Petrovic & Zora Modrusan & Robert B. Faryabi, 2024. "Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    13. Elisa Setten & Alessandra Castagna & Josué Manik Nava-Sedeño & Jonathan Weber & Roberta Carriero & Andreas Reppas & Valery Volk & Jessica Schmitz & Wilfried Gwinner & Haralampos Hatzikirou & Friedrich, 2022. "Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    14. Dafne Ibarra-Morales & Michael Rauer & Piergiuseppe Quarato & Leily Rabbani & Fides Zenk & Mariana Schulte-Sasse & Francesco Cardamone & Alejandro Gomez-Auli & Germano Cecere & Nicola Iovino, 2021. "Histone variant H2A.Z regulates zygotic genome activation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    15. Ryuki Shimada & Yuzuru Kato & Naoki Takeda & Sayoko Fujimura & Kei-ichiro Yasunaga & Shingo Usuki & Hitoshi Niwa & Kimi Araki & Kei-ichiro Ishiguro, 2023. "STRA8–RB interaction is required for timely entry of meiosis in mouse female germ cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    16. Xiang He & Daiqin Xiong & Lei Zhao & Jialong Fu & Lingfei Luo, 2024. "Meningeal lymphatic supporting cells govern the formation and maintenance of zebrafish mural lymphatic endothelial cells," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    17. Guilherme Reis-de-Oliveira & Victor Corasolla Carregari & Gabriel Rodrigues dos Reis de Sousa & Daniel Martins-de-Souza, 2024. "OmicScope unravels systems-level insights from quantitative proteomics data," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    18. Martin Uhrbom & Lars Muhl & Guillem Genové & Jianping Liu & Henrik Palmgren & Ida Alexandersson & Fredrik Karlsson & Alex-Xianghua Zhou & Sandra Lunnerdal & Sonja Gustafsson & Byambajav Buyandelger & , 2024. "Adipose stem cells are sexually dimorphic cells with dual roles as preadipocytes and resident fibroblasts," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    19. Maria J. Garcia-Leon & Cristina Liboni & Vincent Mittelheisser & Louis Bochler & Gautier Follain & Clarisse Mouriaux & Ignacio Busnelli & Annabel Larnicol & Florent Colin & Marina Peralta & Naël Osman, 2024. "Platelets favor the outgrowth of established metastases," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    20. Tingting Bo & Jie Li & Ganlu Hu & Ge Zhang & Wei Wang & Qian Lv & Shaoling Zhao & Junjie Ma & Meng Qin & Xiaohui Yao & Meiyun Wang & Guang-Zhong Wang & Zheng Wang, 2023. "Brain-wide and cell-specific transcriptomic insights into MRI-derived cortical morphology in macaque monkeys," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40596-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.