Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance.
Cell Rep
; 25(12): 3329-3341.e5, 2018 12 18.
Article
en En
| MEDLINE
| ID: mdl-30566860
ABSTRACT
Obesity modifies T cell populations in adipose tissue, thereby contributing to adipose tissue inflammation and insulin resistance. Here, we show that Rab4b, a small GTPase governing endocytic trafficking, is pivotal in T cells for the development of these pathological events. Rab4b expression is decreased in adipose T cells from mice and patients with obesity. The specific depletion of Rab4b in T cells causes adipocyte hypertrophy and insulin resistance in chow-fed mice and worsens insulin resistance in obese mice. This phenotype is driven by an increase in adipose Th17 and a decrease in adipose Treg due to a cell-autonomous skew of differentiation toward Th17. The Th17/Treg imbalance initiates adipose tissue inflammation and reduces adipogenesis, leading to lipid deposition in liver and muscles. Therefore, we propose that the obesity-induced loss of Rab4b in adipose T cells may contribute to maladaptive white adipose tissue remodeling and insulin resistance by altering adipose T cell fate.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Tejido Adiposo
/
Linfocitos T Reguladores
/
Proteínas de Unión al GTP rab4
/
Células Th17
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia