Targeting senescent cells alleviates obesity-induced metabolic dysfunction.
Aging Cell
; 18(3): e12950, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-30907060
ABSTRACT
Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug-inducible "suicide" genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra-abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity-related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity-related metabolic dysfunction and its complications.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
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Tejido Adiposo
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Senescencia Celular
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Adipocitos
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Adipogénesis
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Inflamación
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Obesidad
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Aging Cell
Año:
2019
Tipo del documento:
Article