The Pivotal Role of Macrophages in Metabolic Distress

Obesity is a prevalent condition with several associated co-morbidities including the development of metabolic diseases. In obesity there is immune cell infiltration into the white adipose tissue and this is associated with the generation of inflammation and insulin resistance (IR). A large majority of the infiltrating leukocytes in obese adipose tissue are pro-inflammatory macrophages, which upon activation induce a switch in metabolism from oxidative phosphorylation, as is utilised by macrophages in lean adipose tissue, towards aerobic glycolysis. The signalling pathways evoked in the recruited macrophages induce the release of pro-inflammatory cytokines, in signalling pathways which directly interfere with insulin signalling and thus induce a state of IR. As macrophages appear to play such a pivotal role in the generation of IR and are the largest leukocyte population in the adipose tissue, they provide a promising therapeutic target. Indeed, there are several strategies currently being studied to induce a ‘switch’ in macrophages associated with obese adipose tissue, towards the phenotype of those associated with lean adipose tissue, with arguably the most promising being those strategies designed to target the metabolic pathways within the macrophages. This chapter will discuss the polarisation and activation of macrophages within lean and obese adipose tissue and how these cells can be targeted therapeutically.