摘要
In obesity, persistent low-grade inflammation is considered as a major contributor towards the progression to insulin resistance and type 2 diabetes while in lean subjects the immune environment is non-inflammatory. Massive adipose tissue(AT) infiltration by pro-inflammatory M1 macrophages and several T cell subsets as obesity develops leads to the accumulation-both in the AT and systemically-of numerous pro-inflammatory cytokines, including interleukin-1β(IL-1β), tumor necrosis factor a, IL-17 and IL-6 which are strongly associated with the progression of the obese phenotype towards the metabolic syndrome. At the same time, anti-inflammatory M2 macrophages and Th subsets producing the antiinflammatory cytokines IL-10, IL-5 and interferon-γ, including Th2 and T-reg cells are correlated to the maintenance of AT homeostasis in lean individuals. Here, we discuss the basic principles in the control of the interaction between the AT and infiltrating immune cells both in the lean and the obese condition with a special emphasis on the contribution of pro-and antiinflammatory cytokines to the establishment of the insulinresistant state. In this context, we will discuss the current knowledge about alterations in the levels on pro-and antiinflammatory cytokines in obesity, insulin resistance and type 2 diabetes mellitus, in humans and animal models. Finally, we also briefly survey the recent novel therapeutic strategies that attempt to alleviate or reverse insulin resistance and type 2 diabetes via the administration of recombinant inhibitory antibodies directed towards some pro-inflammatory cytokines.
In obesity, persistent low-grade inflammation is considered as a major contributor towards the progression to insulin resistance and type 2 diabetes while in lean subjects the immune environment is non-inflammatory. Massive adipose tissue(AT) infiltration by pro-inflammatory M1 macrophages and several T cell subsets as obesity develops leads to the accumulation-both in the AT and systemically-of numerous pro-inflammatory cytokines, including interleukin-1β(IL-1β), tumor necrosis factor a, IL-17 and IL-6 which are strongly associated with the progression of the obese phenotype towards the metabolic syndrome. At the same time, anti-inflammatory M2 macrophages and Th subsets producing the antiinflammatory cytokines IL-10, IL-5 and interferon-γ, including Th2 and T-reg cells are correlated to the maintenance of AT homeostasis in lean individuals. Here, we discuss the basic principles in the control of the interaction between the AT and infiltrating immune cells both in the lean and the obese condition with a special emphasis on the contribution of pro-and antiinflammatory cytokines to the establishment of the insulinresistant state. In this context, we will discuss the current knowledge about alterations in the levels on pro-and antiinflammatory cytokines in obesity, insulin resistance and type 2 diabetes mellitus, in humans and animal models. Finally, we also briefly survey the recent novel therapeutic strategies that attempt to alleviate or reverse insulin resistance and type 2 diabetes via the administration of recombinant inhibitory antibodies directed towards some pro-inflammatory cytokines.
基金
Supported by The Franco--Brazilian CAPES/COFECUB colla-boration program Me797-14
supported by a CAPES postdoctoral fellowship
