Vacurova 2022 Nat Commun
|Vacurova E, Trnovska J, Svoboda P, Skop V, Novosadova V, Reguera DP, Petrezselyová S, Piavaux B, Endaya B, Spoutil F, Zudova D, Stursa J, Melcova M, Bielcikova Z, Werner L, Prochazka J, Sedlacek R, Huttl M, Hubackova SS, Haluzik M, Neuzil J (2022) Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice. https://doi.org/10.1038/s41467-022-29486-z|
» Nat Commun 13:1866. PMID: 35387987 Open Access
Vacurova Eliska, Trnovska Jaroslava, Svoboda Petr, Skop Vojtech, Novosadova Vendula, Reguera David Pajuelo, Petrezselyova Silvia, Piavaux Benoit, Endaya Berwini, Spoutil Frantisek, Zudova Dagmar, Stursa Jan, Melcova Magdalena, Bielcikova Zuzana, Werner Lukas, Prochazka Jan, Sedlacek Radislav, Huttl Martina, Hubackova Sona Stemberkova, Haluzik Martin, Neuzil Jiri (2022) Nat Commun
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.
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Diabetes
Organism: Mouse Tissue;cell: Fat Preparation: Intact cells
Coupling state: LEAK, ROUTINE