Invariant natural killer T cells (iNKT cells) have immunoregulatory roles in physiological and pathological settings. In Immunity, Lynch et al. show that iNKT cells regulate body weight and metabolic state by modulating inflammation in adipose tissue. Healthy human and mouse adipose tissues show considerable enrichment for iNKT cells but these cells are replaced by inflammatory macrophages as the adipose tissue expands during obesity. Mice that lack iNKT cells, such as Jα18- or CD1d-deficient mice, have enhanced weight gain, insulin resistance and fatty livers when kept on a high-fat diet, relative to that of their wild-type counterparts. Adoptive transfer of iNKT cells or activation of iNKT cells through injection of α-galactosylceramide decreases body fat and improves insulin sensitivity in mice fed a high-fat diet. The iNKT cells may directly affect adipocytes or act indirectly by modulating macrophage function through their production of anti-inflammatory cytokines such as interleukin 4 (IL-4) and IL-10.

Immunity 37, 574–587 (2012)