IL-33 in obesity: where do we go from here?

Area of Science:

• Immunology
• Metabolic Diseases
• Adipose Tissue Biology

Background:

• Interleukin-33 (IL-33) is an IL-1 family cytokine linked to type 2 immunity and adipose tissue homeostasis.
• In obesity, adipose tissue exhibits increased IL-33 expression but reduced immune cells like innate lymphoid cells 2, alternatively activated macrophages, and regulatory T cells.
• This leads to a failure in maintaining adipose tissue homeostasis despite elevated IL-33 levels.

Purpose of the Study:

• To review the mechanisms behind the impaired action of endogenous IL-33 in obese adipose tissue.
• To explore the discrepancy between upregulated IL-33 expression and its inability to resolve obesity-related inflammation.
• To understand why exogenous IL-33 administration ameliorates obesity-associated metabolic and inflammatory alterations.

Main Methods:

• Literature review focusing on IL-33 function in adipose tissue.
• Analysis of studies investigating IL-33 expression and immune cell populations in lean versus obese adipose tissue.
• Examination of research on the effects of exogenous IL-33 treatment in obesity models.

Main Results:

• Adipose tissue IL-33 expression is increased in obesity.
• Key immune cells crucial for adipose tissue homeostasis are diminished in obese adipose tissue.
• Exogenous IL-33 administration effectively reverses obesity-related inflammatory and metabolic dysfunctions.

Conclusions:

• Endogenous IL-33 signaling in adipose tissue is impaired during obesity.
• The therapeutic benefits of IL-33 in obesity appear to stem from exogenous administration, not endogenous production.
• Further research is needed to elucidate the specific mechanisms of IL-33 dysfunction in obesity.