INS and obesity due to melanocortin 4 receptor deficiency: Indeed, macrophages account for more than 50% of the immune cells infiltrating adipose tissue in obesity,36 and their accumulation in obese VAT is preceded by local enrichment of CD8 T cells.12 Macrophages secrete the majority of inflammatory cytokines,37 and they are polarized toward a unique proinflammatory phenotype, which can be induced by external stimuli (ie, glucose, insulin, and palmitate).38 Defining both macrophages and T cell dynamics of infiltration in time and space, as well as the assessment of their local interactions, is crucial to elucidate the immune mechanisms of IR.