IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis.
Cell Metab
; 26(1): 171-184.e6, 2017 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-28683285
ABSTRACT
Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance. We demonstrate that in mice obesity promotes expansion of a distinct, interleukin-6 receptor (IL6R)a-expressing NK subpopulation, which also expresses a number of other myeloid lineage genes such as the colony-stimulating factor 1 receptor (Csf1r). Selective ablation of this Csf1r-expressing NK cell population prevents obesity and insulin resistance. Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of these myeloid signature NK cells, protecting from obesity, insulin resistance, and obesity-associated inflammation. Also in humans IL6Ra+ NK cells increase in obesity and correlate with markers of systemic low-grade inflammation, and their gene expression profile overlaps with characteristic gene sets of NK cells in obese mice. Collectively, we demonstrate that obesity-associated inflammation and metabolic disturbances depend on interleukin-6/Stat3-dependent formation of a distinct NK population, which may provide a target for the treatment of obesity, metaflammation-associated pathologies, and diabetes.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
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Interleucina-6
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Metabolismo Energético
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Factor de Transcripción STAT3
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Glucosa
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Inflamación
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Obesidad
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Animals
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Humans
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Male
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2017
Tipo del documento:
Article