Obesity and dysregulated central and peripheral macrophage–neuron cross-talk

The involvement of macrophages in the pathogenesis of obesity has been recognized since 2003. Early studies mostly focused on the role of macrophages in adipose tissue (AT) and in obesity-associated chronic low-grade inflammation. Lately, AT macrophages were shown to undergo intrinsic metabolic changes that affect their immune function (i.e., immunometabolism), corresponding to their unique properties along the range of pro- versus anti-inflammatory activity. In parallel, recent studies in mice revealed critical neuronal–macrophage interactions, both in the CNS and in peripheral tissues, including in white and brown AT. These intercellular activities impinge on energy and metabolic homeostasis, partially by also engaging adipocytes in a neuronal–macrophage–adipocyte ménage à trois. Finally, neuropeptides (NP), such as NPY and appetite-reducing NPFF, may prove as mediators in such intercellular network. In this concise review, we highlight some of these recent insights on adipose macrophage immunometabolism, as well as central and peripheral neuronal–macrophage interactions with emphasis on their impact on adipocyte biology and whole-body metabolism. We also discuss the expanding view on the role of the NP, NPY and NPFF, in obesity.