Naᵥ1.8+ Visceral Afferent Neurons: Roles in Metabolism and Inflammation

dc.contributor.advisorScherer, Philippen
dc.contributor.committeeMemberHooper, Lora V.en
dc.contributor.committeeMemberMangelsdorf, David J.en
dc.contributor.committeeMemberZinn, Andrew R.en
dc.contributor.committeeMemberElmquist, Joelen
dc.creatorUdit, Swalpa 1985-en 2014
dc.description.abstractThe increasing prevalence of obesity and its related comorbidities are major health issues facing western societies. Obesity involves a long-term, chronic perturbation of energy balance, in which food intake is not properly matched to calories expended. It is also closely linked with low-grade inflammation characterized by increased levels of circulating inflammatory cytokines and acute-phase reactants, concomitant with the activation of a network of inflammatory signaling pathways. As vagal afferents are a neuronal population that can rapidly respond to both food-related stimuli as well as inflammatory agents and cytokines, I hypothesized that intact vagal afferent function may be required for proper regulation of energy balance and particularly diet-induced inflammation. The sensory component of the vagus nerve has long been considered the main neural relay by which nutritional signals from the gut reach brain sites maintaining homeostasis. To study the function of this neuronal population, we generated a genetic mouse model with specific ablation of sensory vagal neurons by driving expression of diphtheria toxin (DTA) in a Cre-dependent manner through crossing the DTA mouse, which expresses DTA upon Cre activity, with the well-characterized Naᵥ1.8-Cre mouse, which expresses Cre recombinase under the control of Naᵥ1.8, a voltage gated sodium channel present only in peripheral sensory neurons, including 80% of vagal sensory afferent neurons Metabolic phenotyping of these ablated mice in comparison to control littermates did not reveal differences in body weight or food intake on chow diet. However, input from vagal afferents does appear to be important for linking ingested nutrients to acute changes in energy expenditure. This work also suggests that vagal afferents may be involved in checking inflammation to certain stimuli, possibly dietary high fat. As activity of vagal afferents has been shown to be decreased in obesity, dysfunction in this group of neurons could contribute to the diet induced inflammation associated with obesity.en
dc.subjectAfferent Pathwaysen
dc.subjectNeurons, Afferenten
dc.subjectSodium Channelsen
dc.subjectVagus Nerveen
dc.titleNaᵥ1.8+ Visceral Afferent Neurons: Roles in Metabolism and Inflammationen
dc.type.materialtexten School of Biomedical Sciencesen Biologyen Southwestern Medical Centeren of Philosophyen


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