The NLRP3 inflammasome regulates adipose tissue metabolism Academic Article uri icon

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abstract

  • Adipose tissue regulates metabolic homeostasis by participating in endocrine and immune responses in addition to storing and releasing lipids from adipocytes. Obesity skews adipose tissue adipokine responses and degrades the coordination of adipocyte lipogenesis and lipolysis. These defects in adipose tissue metabolism can promote ectopic lipid deposition and inflammation in insulin-sensitive tissues such as skeletal muscle and liver. Sustained caloric excess can expand white adipose tissue to a point of maladaptation exacerbating both local and systemic inflammation. Multiple sources, instigators and propagators of adipose tissue inflammation occur during obesity. Cross-talk between professional immune cells (i.e. macrophages) and metabolic cells (i.e. adipocytes) promote adipose tissue inflammation during metabolic stress (i.e. metaflammation). Metabolic stress and endogenous danger signals can engage pathogen recognition receptors (PRRs) of the innate immune system thereby activating pro-inflammatory and stress pathways in adipose tissue. The Nod-like receptor protein 3 (NLRP3) inflammasome can act as a metabolic danger sensor to a wide range of pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). Activation of the NLRP3 inflammasome facilitates caspase-1 dependent production of the pro-inflammatory cytokines IL-1β and IL-18. Activation of the NLRP3 inflammasome can promote inflammation and pyroptotic cell death, but caspase-1 is also involved in adipogenesis. This review discusses the role of the NLRP3 inflammasome in adipose tissue immunometabolism responses relevant to metabolic disease. Understanding the potential sources of NLRP3 activation and consequences of NLRP3 effectors may reveal therapeutic opportunities to break or fine-tune the connection between metabolism and inflammation in adipose tissue during obesity.

publication date

  • March 27, 2020