The role of macrophage migration inhibitory factor in obesity-associated type 2 diabetes in mice

Macrophage migration inhibitory factor (MIF) is implicated in the pathogenesis of several inflammationrelated diseases, including obesity and type 2 diabetes (T2D). However, MIF deficiency itself promotes obesity and glucose intolerance in mice. Here we show that the introduction of a high-fat diet (HFD) further aggravates the parameters of obesity-associated T2D: weight gain and glucose intolerance. Furthermore, in contrast to MIF-KO mice on standard chow, HFD-fed MIF-KO mice develop insulin resistance. Although the clinical signs of obesity-associated T2D are upgraded, inflammation in MIF-deficient mice on HFD is significantly lower. These results imply that MIF possesses a complex role in glucose metabolism and the development of obesity-related T2D. However, the downregulation of inflammation upon MIF inhibition could be a useful tool in short-term T2D therapy for preventing pancreatic islet deterioration. [Projekat Ministarstva nauke Republike Srbije, br. 173013