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Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice
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SYSNO ASEP 0556801 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice Author(s) Vačurová, Eliška (BTO-N) ORCID
Trnovská, J. (CZ)
Svoboda, P. (CZ)
Skop, V. (US)
Novosadová, Vendula (UMG-J)
Reguera, David Pajuelo (UMG-J)
Petrezselyova, Silvia (UMG-J)
Piavaux, Benoit (UMG-J)
Endaya, Berwini (BTO-N)
Špoutil, František (UMG-J)
Zudová, Dagmar (UMG-J)
Štursa, Jan (BTO-N)
Melčová, M. (CZ)
Bielcikova, Z. (CZ)
Werner, Lukáš (BTO-N)
Procházka, Jan (UMG-J) ORCID
Sedláček, Radislav (UMG-J) RID
Hüttl, M. (CZ)
Štemberková-Hubáčková, Soňa (BTO-N)
Haluzík, M. (CZ)
Neužil, Jiří (BTO-N) RIDNumber of authors 21 Article number 1866 Source Title Nature Communications. - : Nature Publishing Group
Roč. 13, č. 1 (2022)Number of pages 17 s. Language eng - English Country GB - United Kingdom Keywords mitotic clonal expansion ; body-composition changes ; adipose-tissue ; cellular senescence ; insulin-resistance Subject RIV FB - Endocrinology, Diabetology, Metabolism, Nutrition OECD category Endocrinology and metabolism (including diabetes, hormones) R&D Projects GA18-02550S GA ČR - Czech Science Foundation (CSF) GA18-10832S GA ČR - Czech Science Foundation (CSF) GA20-05942S GA ČR - Czech Science Foundation (CSF) GX21-04607X GA ČR - Czech Science Foundation (CSF) NV17-30138A GA MZd - Ministry of Health (MZ) LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001775 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure Czech-BioImaging - 90062 - Ústav molekulární genetiky AV ČR, v. v. i. Method of publishing Open access Institutional support BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000779311200023 EID SCOPUS 85127681413 DOI 10.1038/s41467-022-29486-z Annotation 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2023 Electronic address https://www.nature.com/articles/s41467-022-29486-z
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