The distribution and utilization of fat in different body compartments is subject to exquisite regulation, and it is hard to conceive how this might be achieved purely by the local effects of circulating humoral factors such as insulin. Many other body systems are controlled by the antagonistic arms of the autonomic nervous system, so why not fat metabolism too? Although histological evidence for the innervation of white adipose tissue (WAT) — the principal site for energy storage in mammals — has long existed, extensive sympathetic innervation of WAT was confirmed only recently (see further reading). Now, in the November issue of the Journal of Clinical Investigation, Kreier et al. demonstrate for the first time that WAT receives parasympathetic innervation.

Using a transneuronal retrograde tracer — pseudorabies virus (PRV) — in combination with selective sympathetic denervation, Kreier et al. revealed that fat pads receive direct parasympathetic innervation from the vagal motor nuclei in the brain stem. The sympathetic innervation of WAT is active when the body is in a catabolic, energy-spending state, and the authors hypothesized that parasympathetic control might take over during anabolic states, thereby controlling the build-up of adipose tissue. In keeping with this idea, local parasympathetic denervation by vagotomy was shown to reduce the levels of insulin-mediated glucose and free-fatty-acid uptake by the vagotomized retroperitoneal fat pads by 33 and 36%, respectively. It was also shown to increase the activity of hormone-sensitive lipase, a catabolic enzyme responsible for hydrolysing triglyceride in adipose tissue, and to lead to a decrease in the level of leptin mRNA.

In an extension of the retrograde labelling technique, Kreier et al. were able to demonstrate somatotopy within the projections of the autonomic nervous system to WAT. So, it seems not only that parasympathetic innervation of adipocytes can directly promote energy storage, but furthermore that the selective activation of somatotopically defined pathways might be able to direct storage to specific locations. The challenge will now be to see whether therapeutic strategies might be devised that can selectively regulate the balance of autonomic control in diseases involving obesity.