Obesity is associated with a state of chronic low-grade inflammation and the present invention establishes that adipose-resident natural killer T (NKT) cells attenuate inflammation in adipose tissue and improves systemic glucose homeostasis in mice at different stages of obesity. Accordingly, the present invention provides methods of treating type-2 diabetes or those at risk for type-2 diabetes using activators of adipose-resident NKT cells. Such activators include particular glycolipids (e.g., a-galactosylceramide and its analogs other than sulfated analogs) and cytokines that promote M2 macrophage polarization. The invention also includes methods to screen for activators of adipose-resident NKT cells.
