Activation of Adipose Tissue Macrophages in Obese Mice does not Require Lymphocytes

Macrophages which infiltrate adipose tissue and secrete pro-inflammatory cytokines may be responsible for obesity-induced insulin resistance. However, why macrophages migrate into adipose tissue and become activated remains unknown, though some studies suggest this may be regulated by T and B lymphocytes. In the present study, we test whether T and B lymphocytes and NK cells are necessary for the obesity-induced activation of macrophages in adipose tissue. NOD/SCID/IL2-receptor gamma-chain knockout (NSG) mice, which lack mature T and B lymphocytes and NK cells, were made obese by selectively reducing litters and weaning onto a high-fat diet. Mice were then maintained on the diet for 10-11 weeks. Adipose tissue from obese NSG mice had more activated macrophages than non-obese mice. These macrophages were found in “crown like structures” surrounding adipocytes, and expressed higher levels of the inflammatory cytokine TNFα. However, obesity did not impair glucose tolerance in the NSG mice. These studies demonstrate that T and B lymphocytes and NK cells are not necessary for adipose tissue macrophage activation in obese mice. T and B lymphocytes and/or NK cells may be necessary for the development of obesity-induced impaired glucose tolerance.