Abstract
Obesity modifies Tcell 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 Tcells for the development of these pathological events. Rab4b expression is decreased in adipose Tcells from mice and patients with obesity. The specific depletion of Rab4b in Tcells 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 Tcells may contribute to maladaptive white adipose tissue remodeling and insulin resistance by altering adipose Tcell fate.
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