Obesity is associated with a state of chronic low-grade inflammation. This abnormal inflammation state may cause metabolic dysfunction. Many studies have supported the claim that immune cells such as adipose tissue macrophage and invariant natural killer T-cells (iNKT) are related to the development of metabolic diseases like diabetes. It has recently been reported that while human adenovirus 36 (Ad36) infection is associated with human obesity, it also helps to improve the serum level of lipid factors (glycemic control). However, the detailed cellular mechanism remains unclear. This study (The Journal of Clinical Investigation, 2012;122:3343-54) showed that iNKT cell-deficient mice on a low-fat diet used as a control for high-fat diet boasted insulin resistance phenotype without adipose tissue inflammation. The results of this study offer insight into the possibility of a novel role for iNKT related to the improvement of metabolic diseases, especially insulin resistance, and hint that Ad36-induced inflammation may be associated with iNKT in adipose tissue, while also playing a role in the improvement of glycemic control.