Abstract 59: Altering Levels of Invariant Natural Killer T Cells Does Not Improve Adipose Tissue Inflammation or Insulin Sensitivity in Diet-Induced Obesity
Obesity is a chronic inflammatory state characterized by adipose tissue immune cell infiltration. While macrophages are a key player, recent evidence also implicates T lymphocytes in adipose inflammation. Natural killer T (NKT) cells are a specialized lymphocyte subset expressing natural killer cell properties and T cell receptors (TCR). The invariant NKT (iNKT) cell has a limited TCR repertoire (Vα14/Jα18) and recognizes lipid antigens. Existing data on the role of iNKT cells in obesity is inconclusive. We hypothesized that lipid antigen recognition in obese adipose tissue by iNKT cells contributes to inflammation and insulin resistance. To evaluate whether lack of iNKT cells protects from obesity and its complications, Jα18-/-Ldlr-/- mice lacking iNKT cells were placed on a high fat, high carbohydrate diabetogenic diet +0.15% cholesterol (DDC) for 16 weeks. Effects on body weight, dyslipidemia, insulin resistance, visceral adipose tissue macrophage accumulation and systemic inflammation were analyzed. Jα18-/-Ldlr-/- mice gained more weight than control Ldlr-/- mice. Hypertriglyceridemia developed in the Jα18-/- mice without differences in glucose homeostasis. Increased F4/80 and MCP1 gene expression and macrophage Mac2 immunostaining suggested worsened adipose inflammation. No differences in circulating serum amyloid A, an inflammatory marker, were observed. Overall, mice lacking iNKT cells were not protected from becoming obese but had worsened metabolic features. We also evaluated effects of overabundance of iNKT cells on obesity using Vα14 transgenic(Tg) mice. Vα14TgLdlr-/- mice gained 25% more weight on DDC, had increased fat mass on body composition analysis, hepatomegaly, hyperlipidemia and hyperinsulinemia compared to controls. Adipose tissue revealed increased macrophage, chemotactic and cytokine gene expression as well as Mac2 staining. Similar inflammatory changes were also observed in the liver. Thus the Vα14Tg mice also had significantly worsened metabolic features of obesity. These results suggest that the relationship of iNKT cells in metabolism is complex and that simple excess or depletion of these immunological cells is not sufficient to beneficially modify metabolic abnormalities associated with obesity.
- © 2012 by American Heart Association, Inc.