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

Abstract

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 Ca 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.

Fat feeding facilitates hot bodies, but is resistance futile?

“…The findings of Ribeiro et al . () affirm previous findings of CBC hyperactivity in animals fed HFD and suggest that leptin resistance associated with HFD develops in sensory tissues outside of the CNS. The implications of these findings are that hyperleptinaemia does not directly contribute to the maintenance of CBC hyperactivity and related autonomic dysfunction associated with HFD.…”

“…In this issue of The Journal of Physiology , Ribeiro et al . () explore the effects of a HFD on leptin sensitivity in the CBCs and address signalling pathways which may be altered by HFD. Using a combination of sophisticated in vivo and ex vivo techniques, Ribeiro et al .…”

“…The findings of Ribeiro et al . () do not preclude the possibility that hyperleptinaemia contributes to enhanced CBC activity/sensitivity during the initial stages of HFD which persists after the development of leptin resistance; however, further studies using leptin receptor antagonists during HFD are needed to support this supposition. Thus, while selective leptin resistance in the CNS plays a key role in the development of metabolic dysregulation and obesity associated with HFD, the significance of chronic hyperleptinaemia and leptin resistance in the CBCs remains to be determined.…”

Carotid body activity – are we eating our way into the ventilatory pathway?

“…In more recent years, it has become apparent that the chemoreflex control of breathing is sensitive not only to alterations in arterial blood gases, but also to other physiological entities such as leptin, which was elegantly explored recently in an article in this issue of The Journal of Physiology by Ribeiro et al . ().…”

“…() focused on the role of leptin and the leptin receptor ObRb in CB cells. The current study by Ribeiro and colleagues () investigated the effects of leptin on CB ventilatory control and energy metabolism in both obese and normal rats. It is worth noting that both rats and humans express leptin receptors within the CB.…”