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

0556801 - BTÚ 2023 RIV GB eng J - Journal Article
Vačurová, Eliška - Trnovská, J. - Svoboda, P. - Skop, V. - Novosadová, Vendula - Reguera, David Pajuelo - Petrezselyova, Silvia - Piavaux, Benoit - Endaya, Berwini - Špoutil, František - Zudová, Dagmar - Štursa, Jan - Melčová, M. - Bielcikova, Z. - Werner, Lukáš - Procházka, Jan - Sedláček, Radislav - Hüttl, M. - Štemberková-Hubáčková, Soňa - Haluzík, M. - Neužil, Jiří
Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice.
Nature Communications. Roč. 13, č. 1 (2022), č. článku 1866. E-ISSN 2041-1723
R&D Projects: GA ČR(CZ) GA18-02550S; GA ČR(CZ) GA18-10832S; GA ČR(CZ) GA20-05942S; GA ČR(CZ) GX21-04607X; GA MZd(CZ) NV17-30138A; GA MŠMT(CZ) LM2015062; GA MŠMT(CZ) EF16_013/0001775
Research Infrastructure: Czech-BioImaging - 90062
Institutional support: RVO:86652036 ; RVO:68378050
Keywords : mitotic clonal expansion * body-composition changes * adipose-tissue * cellular senescence * insulin-resistance
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 16.6, year: 2022
Method of publishing: Open access
https://www.nature.com/articles/s41467-022-29486-z

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.
Permanent Link: http://hdl.handle.net/11104/0331426