Neuro-immune interactions in obesity

For the past few decades, obesity has emerged as one of the major complex diseases affecting human populations. Despite recent breakthroughs in ameliorating some of the complications associated with this disease, there are still no effective therapies against obesity To understand obesity one must know how the adipose tissue (AT) is regulated in normal and affected conditions. Our knowledge on AT biology has grown significantly in the last few years. This knowledge has resulted in a clearer picture of how obesity shapes the AT. In this regard, we have decided to focus our work on one important aspect of AT biology: its neuro-immune regulation. More specifically, we set out to understand if signals originating from the sympathetic nervous system (SNS) can modulate the adipose mass, and if such signaling may be regulated at the immunological level. Here we show that sympathetic nerve bundles target the subcutaneous white AT (WAT). Furthermore, we demonstrate that the sympathetic axons in the WAT mediate the lipolytic response to leptin. Importantly, local ablation of the SNS in WAT resulted in decreased leptin activity and blunted lipolysis. Conversely, by using optogenetics to selectively activate these sympathetic bundles, we observed a local release of the neurotransmitter norepinephrine (NE) and subsequent fat loss. Our data provide evidence supporting that sympathetic axons in the AT are both necessary and sufficient for leptin-driven lipolysis in WAT. Obesity has long been associated with low-grade inflammation in peripheral tissues and in the central nervous system (CNS). We have observed that obesity-associated low-grade inflammation also occurs in the SNS. By using multiphoton microscopy tools, we demonstrate that sympathetic axons in WAT are populated by a discrete population of macrophages with cellular characteristics different from those of the macrophages in the surrounding AT. Such Sympathetic-neuron Associated Macrophages (SAM) exhibit profuse dendritiform processes, which dynamically extend and ...