Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance

Cell Rep. 2018 Dec 18;25(12):3329-3341.e5. doi: 10.1016/j.celrep.2018.11.083.


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.

Keywords: adipose tissue; ectopic lipids; endocytosis; immunometabolism; small GTPase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue / pathology
  • Adipose Tissue / physiopathology*
  • Aging / pathology
  • Animals
  • CD3 Complex / metabolism
  • Cell Polarity
  • Fatty Acids / blood
  • Glucose Intolerance / complications
  • Humans
  • Inflammation / pathology
  • Insulin Resistance*
  • Lipid Metabolism
  • Mice, Knockout
  • Obesity / blood
  • Obesity / complications
  • Obesity / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*
  • rab4 GTP-Binding Proteins / deficiency*
  • rab4 GTP-Binding Proteins / genetics
  • rab4 GTP-Binding Proteins / metabolism


  • CD3 Complex
  • Fatty Acids
  • RNA, Messenger
  • rab4 GTP-Binding Proteins