Is interleukin-1β a culprit in macrophage-adipocyte crosstalk in obesity?

Abstract

Adipose tissue remodeling occurs in obesity, characterized by adipocyte hypertrophy and increased infiltration of macrophages which also shift to a proinflammatory phenotype. Factors derived from these macrophages significantly alter adipocyte function, such as repressing adipogenesis, inducing inflammatory response and desensitizing insulin action. As macrophages produce a cocktail of inflammatory signals, identifying the key factors that mediate the detrimental effects may offer effective therapeutic targets. IL-1β, a major cytokine produced largely by macrophages, is implicated in the development of obesity-associated insulin resistance. In this article, we discuss recent advances in our understanding of the role of IL-1β in macrophage-adipocyte crosstalk in obesity. IL-1β impairs insulin sensitivity in adipose tissue by inhibition of insulin signal transduction. Blocking the activity of IL-1β, its receptor binding or production improves insulin signaling and action in human adipocytes. This is in parallel with a reduction in macrophage-stimulated proinflammatory profile and lipolysis. Targeting IL-1β may be beneficial for protecting against obesity-related insulin resistance at the tissue and systemic levels.

Keywords:

• interleukin-1β
• obesity
• adipose tissue
• macrophage
• adipocyte
• inflammation
• insulin resistance
• cytokine
• chemokine

Abbreviations:

• Akt, protein kinase B
• CCL5, chemokine (C-C motif) ligand-5
• GLUT4, glucose transporter 4
• IL-1β, interleukin-1β
• IL-1Ra, interleukin-1 receptor antagonist
• IL-6, interleukin-6
• IL-8, interleukin-8
• IRS1, insulin receptor substrate 1
• MC, macrophage-conditioned
• MCP-1, monocyte chemotactic protein-1
• NFκB, nuclear factor of κ light polypeptide gene enhancer in B-cells
• NLRP3, nucleotide-binding oligomerization domain
• leucine-rich repeat and pyrin
• domain-containing protein 3
• PI3K, phosphoinositide-3-kinase
• SVF, stromal vascular fraction
• TNFα, tumour necrosis factor-alpha

Acknowledgment

The author thanks colleagues at the Obesity Biology Research Group, University of Liverpool, for their contribution to the research program.

Funding

This work was supported in part by the Medical Research Council (G0801226).