Dysfunctional adipose tissue and low-grade inflammation in the management of the metabolic syndrome: current practices and future advances

Figure 1.. Schematic representation of the metabolic syndrome. The components that are used to define the metabolic syndrome are indicated in light brown. The underlying metabolic derangements are indicated in blue. Interventions can be targeted at the level of one or multiple individual components (indicated with 1) or at the potential underlying causes of the metabolic syndrome (indicated with 2). We have proposed that microvascular dysfunction is an early functional pathway that connects adipose tissue dysfunction to insulin resistance and resulting metabolic derangements, but this is beyond the scope of this review 9. Abbreviations: HDL, high-density lipoprotein.

Figure 2.. Relevant aspects of complement activation and inflammasome activation with their possible interconnection. The inflammasome and the complement system can be activated via so-called danger-associated molecular patterns (DAMPS) and pathogen-associated molecular patterns (PAMPS). Activation of the classical, the lectin, and the alternative pathway of complement activation all result in the activation of complement C3. The alternative pathway functions as an amplification route for all pathways of complement activation. Activation of C3 leads to the generation of C3a and the activation of the terminal effector pathway. Activation of the NOD-like receptor family Pyrin domains-containing protein 3 (NLRP3) inflammasome includes the formation of a cytosolic multiprotein complex that activates caspase 1. Caspase 1 cleaves pro-interleukin (IL)-1β into IL-1β. Pharmacological compounds that are used to dampen the effects of inflammasome activation primarily act at the level of IL-1β. In the dotted squares, we have indicated some selected drugs that are already used to target complement and/or inflammasome activation in other diseases. Compstatin inhibits complement activation by binding C3…