The macrophage migration inhibitory factor protein superfamily in obesity and wound repair

The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed. Identifying key molecules involved in obesity may improve treatments for impaired wound repair in both healthy and obese individuals. In addition to storing energy, adipose (fatty) tissue is a major hormone producer and has been recognized to express various cytokines and adipokines. Obesity therefore causes multiple systemic complications, including chronic inflammation, insulin resistance, and impaired wound healing but the molecules and pathways involved are poorly understood. Researchers in Germany and the USA, led by Bong-Sung Kim (RWTH-University Aachen, Yale University), reviewed the data on the roles of two key proteins in adipose tissue function and wound repair. Macrophage migration inhibitory factor contributes to the development of obesity, insulin resistance, and adipose tissue inflammation. D-dopachrome tautomerase reverses insulin resistance and is negatively correlated with obesity. However, the two proteins may play complementary roles in wound healing.