| First Author | Gilleron J | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 12 | Pages | 3329-3341.e5 |
| PubMed ID | 30566860 | Mgi Jnum | J:271040 |
| Mgi Id | MGI:6278381 | Doi | 10.1016/j.celrep.2018.11.083 |
| Citation | Gilleron J, et al. (2018) Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance. Cell Rep 25(12):3329-3341.e5 |
| abstractText | 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. |
