Carotid bodies (CBs) are peripheral chemoreceptors that sense changes in blood O2, CO2, and pH levels. Apart from ventilatory control, these organs are deeply involved in the homeostatic regulation of carbohydrates and lipid metabolism and inflammation. It has been described that CB dysfunction is involved in the genesis of metabolic diseases and that CB overactivation is present in animal models of metabolic disease and in prediabetes patients. Additionally, resection of the CB-sensitive nerve, the carotid sinus nerve (CSN), or CB ablation in animals prevents and reverses diet-induced insulin resistance and glucose intolerance as well as sympathoadrenal overactivity, meaning that the beneficial effects of decreasing CB activity on glucose homeostasis are modulated by target-related efferent sympathetic nerves, through a reflex initiated in the CBs. In agreement with our pre-clinical data, hyperbaric oxygen therapy, which reduces CB activity, improves glucose homeostasis in type 2 diabetes patients. Insulin, leptin, and pro-inflammatory cytokines activate the CB. In this manuscript, we review in a concise manner the putative pathways linking CB chemoreceptor deregulation with the pathogenesis of metabolic diseases and discuss and present new data that highlight the roles of hyperinsulinemia, hyperleptinemia, and chronic inflammation as major factors contributing to CB dysfunction in metabolic disorders.

Respiratory disturbances present in Parkinson's disease (PD) are not well understood. Thus, studies in animal models aimed to link brain dopamine (DA) deficits with respiratory impairment are needed. Adult Wistar rats were lesioned with injection of 6-hydroxydopamine (6-OHDA) into the third cerebral ventricle. Two weeks after hypoxic test was performed in whole-body plethysmography chamber, phrenic (PHR) and hypoglossal (HG) nerve activities were recorded in normoxic and hypoxic conditions in anesthetized, vagotomized, paralyzed and mechanically ventilated rats. The effects of activation and blockade of dopaminergic carotid body receptors were investigated during normoxia in anesthetized spontaneously breathing rats. 6-OHDA injection affected resting respiratory pattern in awake animals: an increase in tidal volume and a decrease in respiratory rate had no effect on minute ventilation. Hypoxia magnified the amplitude and minute activity of the PHR and HG nerve of 6-OHDA rats. The ratio of pre-inspiratory to inspiratory HG burst amplitude was reduced in normoxic breathing. Yet, the ratio of pre-inspiratory time to total time of the respiratory cycle was increased during normoxia. 6-OHDA lesion had no impact on DA and domperidone effects on the respiratory pattern, which indicate that peripheral DA receptors are not affected in this model. Analysis of monoamines confirmed substantial striatal depletion of dopamine, serotonin and noradrenaline (NA) and reduction of NA content in the brainstem. In bilateral 6-OHDA model changes in activity of both nerves: HG (linked with increased apnea episodes) and PHR are present. Demonstrated respiratory effects could be related to specific depletion of DA and NA.