RT info:eu-repo/semantics/article T1 High fat diet blunts the effects of leptin on ventilation and on carotid body activity A1 Ribeiro, Maria J. A1 Sacramento, Joana F. A1 Gallego Martín, María Teresa A1 Olea Fraile, Elena A1 Melo, Bernardete F. A1 Guarino, Maria P. A1 Yubero Benito, Sara A1 Obeso Cáceres, Ana María de la Luz A1 Conde, Silvia V. K1 Ventilation K1 Ventilation K1 Leptin K1 Leptina K1 Carotid body K1 Cuerpo carotídeo K1 Adenosine K1 Adenosina AB Leptin plays a role in the control of breathing, acting mainly on central nervous system structures. Leptin receptors are expressed in the carotid body (CB) and this finding has been associated with a putative physiological role of leptin in the regulation of CB function. Since, the CBs are implicated in energy metabolism, here we tested the effects of different concentrations of leptin administration on ventilatory parameters and on carotid sinus nerve (CSN) activity in control and high-fat (HF) diet fed rats, in order to clarify the role of leptin in ventilation control in metabolic disease states. We also investigated the expression of leptin receptors and the neurotransmitters involved in leptin signalling in the CBs. We found that in non-disease conditions, leptin increases minute ventilation in both basal and hypoxic conditions. However, in the HF model, the effect of leptin in ventilatory control is blunted. We also observed that HF rats display an increased frequency of CSN discharge in basal conditions that is not altered by leptin, in contrast to what is observed in control animals. Leptin did not modify intracellular Ca2+ in CB chemoreceptor cells, but it produced an increase in the release of adenosine from the whole CB. We conclude that CBs represent an important target for leptin signalling, not only to coordinate peripheral ventilatory chemoreflexive drive, but probably also to modulate metabolic variables. We also concluded that leptin signalling is mediated by adenosine release and that HF diets blunt leptin responses in the CB, compromising ventilatory adaptation. PB The Physiological Society SN 1469-7793 YR 2018 FD 2018 LK https://uvadoc.uva.es/handle/10324/46962 UL https://uvadoc.uva.es/handle/10324/46962 LA eng NO The Journal of Physiology, 2018, vol. 596, n. 15. p. 3187-3199 NO Producción Científica DS UVaDOC RD 24-dic-2024