Linking obesity with type 2 diabetes: the role of T-bet

Obesity is a major predisposing factor for the development of type 2 diabetes (T2D) and is an escalating public health issue around the world. The transition from obesity to T2D is preceded by the induction of a state of insulin resistance, which occurs in response to genetic factors and environmental influences, such as diet. Recent advances have implicated inflammatory immune cells and cytokines as critical pathogenic mediators of insulin resistance and T2D. In particular proinflammatory T helper (Th) 1 cells and M1 macrophages are recruited to adipose tissue in response to high fat diet and directly promote the development of insulin resistance. The function of these two cell types is linked by the actions of the cytokine interferon (IFN). and one of its major transcriptional regulators T-bet. Recent studies in animal models of T2D demonstrate that T-bet is critical for the development of insulin resistance in response to high fat diet as T-bet-deficient animals are protected from the development of insulin resistance. These data indicate that T-bet and type 1 immunity may constitute novel sites of therapeutic intervention for the treatment of insulin resistance and T2D, in obese human patients.