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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
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    References listed on IDEAS

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    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.
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