title: 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.
authors.affiliation: Department of Obesity and Endocrinology, Institute of Ageing and Chronic Disease, University of Liverpool , Liverpool, UK.
authors.forename: Chen
authors.initials: C
authors.lastname: Bing
keywords: Akt, protein kinase B; CCL5, chemokine (C-C motif) ligand-5; GLUT4, glucose transporter 4; IL-1Ra, interleukin-1 receptor antagonist; IL-1β, interleukin-1β; 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; PI3K, phosphoinositide-3-kinase; SVF, stromal vascular fraction; TNFα, tumour necrosis factor-alpha; adipocyte; adipose tissue; chemokine; cytokine; domain-containing protein 3; inflammation; insulin resistance; interleukin-1β; leucine-rich repeat and pyrin; macrophage; obesity