Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 04 2022
06 04 2022
Historique:
received:
25
08
2020
accepted:
17
03
2022
entrez:
7
4
2022
pubmed:
8
4
2022
medline:
9
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35387987
doi: 10.1038/s41467-022-29486-z
pii: 10.1038/s41467-022-29486-z
pmc: PMC8987092
doi:
Substances chimiques
Tamoxifen
094ZI81Y45
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1866Informations de copyright
© 2022. The Author(s).
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