Interaction between nesfatin-1 and oxytocin in the modulation of the swallowing reflex

Abstract

Inhibition of the swallowing reflex by nesfatin-1 2 47 Abstract 48 49 Nesfatin-1, an 82-amino acid peptide encoded by the secreted precursor nucleobinin-2 50 (NUCB2), exerts potent anorexigenic action independently of leptin signaling. This propensity has 51 propelled this peptide and its analogues as potential anti-obesity drug candidates. However, a more 52 extensive comprehension of its biological actions is needed prior to envisaging its potential use in the 53 treatment of metabolic diseases. Swallowing is an essential motor component of ingestive behavior, 54 which induces the propulsion of the alimentary bolus from the mouth to the esophagus. The dorsal 55 swallowing group (DSG) which constitutes a part of the central pattern generator of swallowing 56 (SwCPG) is located within the solitary tract nucleus (STN), a region reported to contain nesfatin-57 1/NUCB2 expressing neurons. In this context, we investigate here the possible effects of nesfatin-1 58 on swallowing discharge. Nesfatin-1 dose-dependently inhibited swallowing reflex and activated 59 neurons located in the DSG region. In addition, we provide evidences that strongly suggest that this 60 nesfatin-1 inhibitory effect involved an oxytocinergic relay. Indeed, oxytocin (OT) injection at the 61 brainstem level inhibited swallowing reflex and OT receptor antagonist prevented nesfatin-1 62 inhibitory action. Altogether, these data constitute the first demonstration that nesfatin-1 modulates 63 swallowing reflex by acting at the brainstem level via an oxytocinergic relay. 64

Nucleobindin 2/nesfatin‐1 expression and colocalisation with neuropeptide Y and cocaine‐ and amphetamine‐regulated transcript in the human brainstem

“…According to our results, NUCB2/nesfatin‐1 localisation in the human medullary reticular formation and pontine reticular nucleus is interesting in view of the prominent integrative role of the reticular formation in the control of the autonomic, endocrine and behavioural responses that collectively regulate energy homeostasis 3,60 . Furthermore, Sol and the neighbouring medullary reticular formation are implicated in central control of swallowing and nesfatin‐1 has been reported to modulate the swallowing reflex by acting at the brainstem 69,70 . Because there is no scientific evidence for the functional role of NUCB2/nesfatin‐1 in brainstem reticular formation, this remains to be determined.…”

The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats

“…Therefore, mutual inhibition between the appetite-increasing peptide and satiety peptide to alter reflex swallowing is possible. Other appetite-increasing and satiety peptides also alter the swallowing reflex [5,7,8,26]. In order to elucidate the entire mechanism of swallowing regulation by appetite-regulating substances, a comprehensive understanding, including the interaction of multiple feeding-related substances, is required.…”

“…Our previous study revealed that appetite-enhancing peptides, such as ghrelin and orexin/hypocretin, suppressed reflex swallowing induced by afferent stimulation of the superior laryngeal nerve (SLN) [5,6]. Our previous study and those of others demonstrated that the injection of a satiety peptide such as glucagon like peptide-1 (GLP-1), leptin, oxytocin, or nesfatin-1 into the rat dorsal medulla suppressed reflex swallowing induced by electrical stimulation of the SLN, similarly to appetite-enhancing peptides [7][8][9]. Thus, both appetite-increasing and -satiating substances similarly suppress reflex swallowing.…”