Abstract
The nucleus of the solitary tract (NTS) is critical for the central integration of signals from visceral organs and contains preproglucagon (PPG) neurons, which express leptin receptors in the mouse and send direct projections to the paraventricular nucleus of the hypothalamus (PVH). Here, we visualized projections of PPG neurons in leptin-deficient Lepob/ob mice and found that projections from PPG neurons are elevated compared with controls, and PPG projections were normalized by targeted rescue of leptin receptors in LepRbTB/TB mice, which lack functional neuronal leptin receptors. Moreover, Lepob/ob and LepRbTB/TB mice displayed increased levels of neuronal activation in the PVH following vagal stimulation, and whole-cell patch recordings of GLP-1 receptor-expressing PVH neurons revealed enhanced excitatory neurotransmission, suggesting that leptin acts cell autonomously to suppress representation of excitatory afferents from PPG neurons, thereby diminishing the impact of visceral sensory information on GLP-1 receptor-expressing neurons in the PVH.
Highlights
Effective coordination of metabolic regulatory processes requires integration of hormonal signals with viscerosensory information conveyed from thoracic and abdominal viscera by the vagus nerve
Leptin impacts the activity of nucleus of the solitary tract (NTS) neurons, which appear to express the long form of the leptin receptor (LepRb), and this information may converge onto the paraventricular nucleus of the hypothalamus (PVH) with leptin signals conveyed by other afferent populations (Grill, 2010; Scott et al, 2011)
glucagon-like peptide-1 (GLP-1) fibers are visible at P6, their density is sparse at this age, and the preautonomic compartment of the PVH is nearly devoid of GLP-1 innervation
Summary
Effective coordination of metabolic regulatory processes requires integration of hormonal signals with viscerosensory information conveyed from thoracic and abdominal viscera by the vagus nerve. Sensory components of the vagus innervate the digestive tract and provide afferent projections that target neurons in the nucleus of the solitary tract (NTS). This viscerosensory information is conveyed directly from the NTS to a variety of sites within the central nervous system, including discrete populations of hypothalamic neurons, where they regulate homeostatic processes (Schwartz and Zeltser, 2013; Saper and Stornetta, 2015). It is clear that innervation of the PVH by neurons in the ARH is dependent on exposure to leptin during neonatal life (Bouyer and Simerly, 2013), it remains uncertain if leptin is required for normal development of other afferent neural systems. Because innervation of the PVH by GLP-1 axons occurs during a neonatal period of elevated leptin secretion (Ahima and Flier, 2000; Elson and Simerly, 2015), we used multiple molecular genetic approaches to test the hypothesis that leptin is required to support development of GLP-1 inputs to the PVH
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
