Metabolic regulation of adipose tissue macrophage (ATM) function in obesity and diabetes

SIGNIFICANCE: Obesity and diabetes are associated with chronic activation of inflammatory pathways that are important mechanistic links between insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular disease pathogenesis. The development of these metabolic diseases is associated with changes in the both the number and phenotype of adipose tissue macrophages. Emerging lines of evidence have shown that adipose tissue macrophages (ATM) release pro-inflammatory cytokines similar to classically-activated M1 macrophages, that directly contribute to IR or T2D. In contrast, adipose tissue from lean healthy individuals contains macrophages with a less inflammatory M2 phenotype. Recent Advances: Recent research has shown that macrophage phenotype is linked to profound changes in macrophage cellular metabolism. CRITICAL ISSUES: This review focuses on the role of macrophages in adipose tissue inflammation and obesity, and the metabolic changes in macrophage function that occur with activation that underpin their role in the pathogenesis of IR and T2D. We highlight current targets for altering macrophage metabolism from both within the field of metabolic disease and adipose tissue biology and more widely within inflammatory biology. FUTURE DIRECTIONS: As our knowledge of macrophage metabolic programming in adipose tissue builds, there will be increasing scope for targeting this aspect of macrophage biology as a therapeutic strategy in metabolic diseases