Activation of adipose tissue macrophages in obese mice does not require lymphocytes.

Abstract

Macrophages which infiltrate adipose tissue and secrete proinflammatory cytokines may be responsible for obesity-induced insulin resistance. However, the reason why macrophages migrate into adipose tissue and become activated remains unknown though some studies suggest that this may be regulated by T and B lymphocytes. In this study, it has been tested whether T and B lymphocytes and natural killer (NK) cells were 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 nonobese mice. These macrophages were found in "crown-like structures" surrounding adipocytes, and expressed higher levels of the inflammatory cytokine TNF-α. However, obesity did not impair glucose tolerance in the NSG mice. These studies demonstrated 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.