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

Maria J Ribeiro, Joana F Sacramento, Teresa Gallego-Martin, Elena Olea, Bernardete F Melo, Maria P Guarino, Sara Yubero, Ana Obeso, Silvia V Conde

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Leptin plays a role in the control of breathing, acting mainly on central nervous structures. Leptin receptor is 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 herein 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 both in 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. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)3187-3199
Number of pages13
JournalJournal Of Physiology-London
Volume596
Issue number15
Early online date15 Jan 2018
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • ventilation
  • leptin
  • carotid body
  • carotid sinus nerve
  • adenosine

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