IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29486-z.html
   My bibliography  Save this article

Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice

Author

Listed:
  • Eliska Vacurova

    (Czech Academy of Sciences
    Charles University)

  • Jaroslava Trnovska

    (Institute for Clinical and Experimental Medicine)

  • Petr Svoboda

    (Institute for Clinical and Experimental Medicine
    University of Chemistry and Technology Prague)

  • Vojtech Skop

    (National Institute of Diabetes and Digestive and Kidney Diseases, NIH)

  • Vendula Novosadova

    (Czech Academy of Sciences)

  • David Pajuelo Reguera

    (Czech Academy of Sciences)

  • Silvia Petrezselyová

    (Czech Academy of Sciences)

  • Benoit Piavaux

    (Czech Academy of Sciences)

  • Berwini Endaya

    (Czech Academy of Sciences)

  • Frantisek Spoutil

    (Czech Academy of Sciences)

  • Dagmar Zudova

    (Czech Academy of Sciences)

  • Jan Stursa

    (Czech Academy of Sciences)

  • Magdalena Melcova

    (University of Chemistry and Technology Prague)

  • Zuzana Bielcikova

    (General University Hospital)

  • Lukas Werner

    (Czech Academy of Sciences)

  • Jan Prochazka

    (Czech Academy of Sciences)

  • Radislav Sedlacek

    (Czech Academy of Sciences)

  • Martina Huttl

    (Institute for Clinical and Experimental Medicine)

  • Sona Stemberkova Hubackova

    (Czech Academy of Sciences)

  • Martin Haluzik

    (Institute for Clinical and Experimental Medicine)

  • Jiri Neuzil

    (Czech Academy of Sciences
    Griffith University)

Abstract

Type 2 diabetes mellitus represents a major health problem with increasing prevalence worldwide. Limited efficacy of current therapies has prompted a search for novel therapeutic options. Here we show that treatment of pre-diabetic mice with mitochondrially targeted tamoxifen, a potential anti-cancer agent with senolytic activity, improves glucose tolerance and reduces body weight with most pronounced reduction of visceral adipose tissue due to reduced food intake, suppressed adipogenesis and elimination of senescent cells. Glucose-lowering effect of mitochondrially targeted tamoxifen is linked to improvement of type 2 diabetes mellitus-related hormones profile and is accompanied by reduced lipid accumulation in liver. Lower senescent cell burden in various tissues, as well as its inhibitory effect on pre-adipocyte differentiation, results in lower level of circulating inflammatory mediators that typically enhance metabolic dysfunction. Targeting senescence with mitochodrially targeted tamoxifen thus represents an approach to the treatment of type 2 diabetes mellitus and its related comorbidities, promising a complex impact on senescence-related pathologies in aging population of patients with type 2 diabetes mellitus with potential translation into the clinic.

Suggested Citation

  • Eliska Vacurova & Jaroslava Trnovska & Petr Svoboda & Vojtech Skop & Vendula Novosadova & David Pajuelo Reguera & Silvia Petrezselyová & Benoit Piavaux & Berwini Endaya & Frantisek Spoutil & Dagmar Zu, 2022. "Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29486-z
    DOI: 10.1038/s41467-022-29486-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29486-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29486-z?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. Mikolaj Ogrodnik & Satomi Miwa & Tamar Tchkonia & Dina Tiniakos & Caroline L. Wilson & Albert Lahat & Christoper P. Day & Alastair Burt & Allyson Palmer & Quentin M. Anstee & Sushma Nagaraja Grellsche, 2017. "Cellular senescence drives age-dependent hepatic steatosis," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    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. Jinjie Duan & Wenhui Dong & Guangyan Wang & Wenjing Xiu & Guangyin Pu & Jingwen Xu & Chenji Ye & Xu Zhang & Yi Zhu & Chunjiong Wang, 2023. "Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Imanol Duran & Joaquim Pombo & Bin Sun & Suchira Gallage & Hiromi Kudo & Domhnall McHugh & Laura Bousset & Jose Efren Barragan Avila & Roberta Forlano & Pinelopi Manousou & Mathias Heikenwalder & Domi, 2024. "Detection of senescence using machine learning algorithms based on nuclear features," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Cox, Lynne S., 2022. "Therapeutic approaches to treat and prevent age-related diseases through understanding the underlying biological drivers of ageing," The Journal of the Economics of Ageing, Elsevier, vol. 23(C).

    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:13:y:2022:i:1:d:10.1038_s41467-022-29486-z. 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.