A Tale of Three Systems: Towards a NeuroImmunoEndocrine model of obesity

The prevalence of obesity is on the rise. What was once considered a simple disease of energy imbalance is now recognised as a complex condition perpetuated by neuro- and immuno-pathologies. In this review, we summarise the current knowledge of the neuroimmunoendocrine mechanisms underlying obesity. We examine the pleiotropic effects of leptin action, in addition to its established role in modulation of appetite, and discuss the neural circuitry mediating leptin action, and how this is altered with obesity, both centrally (leptin resistance) and in adipose tissues (sympathetic neuropathy). Finally, we dissect the numerous causal and consequential roles of adipose tissue macrophages in obesity and highlight key recent studies demonstrating their direct role in organismal energy homeostasis.