Introduction: The carotid bodies (CBs), peripheral chemoreceptors defined as O2 sensors, are also involved in energy homeostasis [1,2]. Moreover, CB dysfunction has been implicated in metabolic diseases genesis since the abolishment of its activity, via the resection or neuromodulation of its sensitive nerve, the carotid sinus nerve (CSN), prevents and reverses the pathological features in prediabetes and type 2 diabetes (T2D) animal models [3-5]. Considering that dysmetabolic states are deeply involved with the deregulation of feeding behavior and satiety pathways in the hypothalamus and that insulin, leptin, and dopamine that activate the CB, play important roles in these mechanisms we investigated whether the beneficial impacts of CSN denervation on metabolism include the modulation of feeding behavior and hypothalamic satiety pathways. Material & Methods: Two different strains of rats were used: Wistar rats submitted either to control diet (CTL) or to a high-fat diet (HF, 60% enriched in lipids) and Zucker Diabetic fat (ZDF) rats (fa/fa) submitted to Purina 5008 diet, and its control group (Zucker Lean +/?). After 10 weeks, both groups were submitted to either CSN ablation or sham surgery and followed up during 9 and 7 weeks, respectively. Groups included 5-8 animals per group. Caloric intake, weight gain, whole-body insulin sensitivity, and glucose tolerance were evaluated. Hypothalamic expression of leptin receptors (ObR), dopamine type 2 receptors (D2R), insulin receptors (IR), AKT (protein kinase B), and tyrosine hydroxylase (TH) was evaluated by Western Blot technique. Laboratory care was in accordance with the European Union Directive 2010/63/EU. Experimental protocols were approved by NOVA Medical School Ethics Committee. The significance of the differences between the mean values and SD was calculated by one- and two-way ANOVA with Bonferroni multiple comparison test. Differences were considered significant at p < 0.05. Results: HF animals and ZDF fa/fa animals show increased weight gain, insulin resistance and glucose intolerance. CSN denervation reversed all these pathological features in HF animals but only insulin resistance in ZDF fa/fa animals. HF diet and ZDF fa/fa animals exhibited increased caloric intake by 39.1%, and 100.4%, respectively, effects attenuated by 9.5% and 53.2% with CSN denervation (caloric intake CTL =206.39 Kcal/day; caloric intake lean=303.83 Kcal/day). In the hypothalamus, HF diet significantly decreased the expression of IR, AKT, ObR, and TH by 15.5%, 32.5%, 19.2%, and 28.9%, respectively, and increased the expression of D2R without producing significant changes. CSN denervation attenuated the decreased expression of IR, ObR, and D2R and increased the expression of AKT and TH. ZDF fa/fa animals show an increase in the expression of D2R and IR by 35.3% and 7.2% respectively. CSN denervation also produces a decrease in the expression of TH and AKT by 20.7% and 29.3% respectively, effects attenuated with CSN denervation. Conclusions: CSN denervation positively impacts weight gain and metabolic function in different models of dysmetabolism. We can postulate that it may be in part due to the control of the dopaminergic and insulin pathways at the hypothalamus, and that the CB has a role in the regulation of feeding behavior and satiety.