Kozicz T, Xu L, Geenen B, Gaszner B, Kovacs K, Roubos E (2011) Leptin-receptor-expressing neurons in the non-preganglionic Edinger-Westphal nucleus regulate white and brown adipose tissue. Neuroscience 2011 Abstracts 822.19. Society for Neuroscience, Washington, DC.
Summary: Leptin, produced by white adipose tissue (WAT), is a key factor that regulates food intake and energy expenditure in vertebrates. It conveys information about fat storage in the periphery to the brain. The leptin receptor long form (LepRb) can be found in the non-preganglionic Edinger-Westphal nucleus (npEW) in the midbrain, which is the main site of urocortin 1 (Ucn1) production in the brain. In both mice and rats, intraperitoneal administration of leptin induces an increase in Ucn1 expression in the npEW whereas in mice that lack LepRb (db/db mice), the npEW contains considerably reduced amount of Ucn1. The npEW also responds to acute thermal exposure, indicating a role of this nucleus in thermoregulation. Brown adipose tissue (BAT) is critical to maintain homoeothermia and is centrally controlled via sympathetic outputs. A recent study demonstrates a projection from EW to BAT by using retrograde tracer pseudorabies virus (PRV). In our study, using PRV injection into the WAT of rats, we identified PRV-labeled Ucn1 neurons in the npEW, indicating a connection from npEW to WAT. In order to analyze the involvement of the npEW in the regulation of sympathetic WAT and BAT outputs, we performed the experiment using the neurotoxin saporin. When conjugated to leptin (Lep-SAP), Lep-SAP can selectively kill LepRb-expressing neurons. Wister rats were given injection of either Lep-SAP or a control blank saporin (B-SAP) into the left npEW Results showed that injection of Lep-SAP significantly blunted Ucn1 expression in the npEW. The weights of WAT and BAT were analyzed on both sides. The WAT and BAT weights were increased significantly on the contralateral side in Lep-SAP compared with B-SAP injected rats, however not different on the ipsilateral side. Interestingly, we observed that both WAT and BAT weighed more on the ipsilateral than the contralateral side only in the B-SAP animals. We will further test the effect of lesioning npEW neurons on the function of WAT and BAT by assessing specific WAT and BAT markers by RT-PCR and histology. Taken these data together, we provide evidence that LepRb-expressing neurons in the npEW regulate BAT and WAT most probably via sympathetic circuits.