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High fat diet blunts the effects of leptin on ventilation and on carotid body activity

2018-01-15Journal article Open access
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dc.contributor.authorRibeiro, Maria J.
dc.contributor.authorSacramento, Joana F.
dc.contributor.authorGallego‐Martin, Teresa
dc.contributor.authorOlea, Elena
dc.contributor.authorMelo, Bernardete F.
dc.contributor.authorGuarino, Maria Pedro
dc.contributor.authorYubero, Sara
dc.contributor.authorObeso, Ana
dc.contributor.authorConde, Silvia V.
dc.date.accessioned2025-07-15T14:07:02Z
dc.date.available2025-07-15T14:07:02Z
dc.date.issued2018-01-15
dc.description.abstractKey points Leptin plays a role in the control of breathing, acting mainly on central nervous system; however, leptin receptors have been recently shown to be expressed in the carotid body (CB), and this finding suggests a physiological role for leptin in the regulation of CB function. Leptin increases minute ventilation in both basal and hypoxic conditions in rats. It increases the frequency of carotid sinus nerve discharge in basal conditions, as well as the release of adenosine from the CB. However, in a metabolic syndrome animal model, the effects of leptin in ventilatory control, carotid sinus nerve activity and adenosine release by the CB are blunted. Although leptin may be involved in triggering CB overactivation in initial stages of obesity and dysmetabolism, resistance to leptin signalling and blunting of responses develops in metabolic syndrome animal models. 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.eng
dc.description.sponsorshipThis study was supported by the Portuguese Foundation for Science and Technology grant PTDC/SAU-ORG/111417/2009 to S.C. and by Grants BFU2015-70616R from MINECO-FEDER, Spain. J.F.S. and B.F.M. are supported by PhD Grants from FCT, PD/BD/105890/2014 and PD/BD/128336/2017, respectively.
dc.identifier.citationRibeiro, M.J., Sacramento, J.F., Gallego-Martin, T., Olea, E., Melo, B.F., Guarino, M.P., Yubero, S., Obeso, A. and Conde, S.V. (2018), High fat diet blunts the effects of leptin on ventilation and on carotid body activity. J Physiol, 596: 3187-3199. https://doi.org/10.1113/JP275362
dc.identifier.doi10.1113/jp275362
dc.identifier.issn0022-3751
dc.identifier.issn1469-7793
dc.identifier.urihttp://hdl.handle.net/10400.8/13652
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.relation.hasversionhttps://physoc.onlinelibrary.wiley.com/doi/10.1113/JP275362
dc.relation.ispartofThe Journal of Physiology
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleHigh fat diet blunts the effects of leptin on ventilation and on carotid body activityeng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage3199
oaire.citation.issue15
oaire.citation.startPage3187
oaire.citation.titleThe Journal of Physiology
oaire.citation.volume596
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameGuarino
person.givenNameMaria Pedro
person.identifier.ciencia-idF21A-BD01-2D52
person.identifier.orcid0000-0001-6079-1105
person.identifier.ridB-5594-2015
person.identifier.scopus-author-id56348477000
relation.isAuthorOfPublicationf163d4df-1e45-4278-affa-5994f206becf
relation.isAuthorOfPublication.latestForDiscoveryf163d4df-1e45-4278-affa-5994f206becf

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