Leptin modifies the prosecretory and prokinetic effects of the inflammatory cytokine interleukin-6 on colonic function in Sprague–Dawley rats

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dc.contributor.author Buckley, Maria M.
dc.contributor.author O'Brien, Rebecca L.
dc.contributor.author Devlin, Michelle
dc.contributor.author Creed, Aisling A.
dc.contributor.author Rae, Mark G.
dc.contributor.author Hyland, Niall P.
dc.contributor.author Quigley, Eamonn M.
dc.contributor.author McKernan, Declan P.
dc.contributor.author O'Malley, Dervla
dc.date.accessioned 2017-01-05T15:58:00Z
dc.date.available 2017-01-05T15:58:00Z
dc.date.issued 2016-09-27
dc.identifier.citation Buckley, M. M., O'Brien, R., Devlin, M., Creed, A. A., Rae, M. G., Hyland, N. P., Quigley, E. M. M., McKernan, D. P. and O'Malley, D. (2016) 'Leptin modifies the prosecretory and prokinetic effects of the inflammatory cytokine interleukin-6 on colonic function in Sprague–Dawley rats', Experimental Physiology, 101(12), pp. 1477-1491. doi: 10.1113/EP085917 en
dc.identifier.volume 101 en
dc.identifier.issued 12 en
dc.identifier.startpage 1477 en
dc.identifier.endpage 1491 en
dc.identifier.issn 0958-0670
dc.identifier.uri http://hdl.handle.net/10468/3434
dc.identifier.doi 10.1113/EP085917
dc.description.abstract Leptin ameliorates the prosecretory and prokinetic effects of the pro-inflammatory cytokine interleukin-6 on rat colon. Leptin also suppresses the neurostimulatory effects of irritable bowel syndrome plasma, which has elevated concentrations of interleukin-6, on enteric neurons. This may indicate a regulatory role for leptin in immune-mediated bowel dysfunction. In addition to its role in regulating energy homeostasis, the adipokine leptin modifies gastrointestinal (GI) function. Indeed, leptin-resistant obese humans and leptin-deficient obese mice exhibit altered GI motility. In the functional GI disorder irritable bowel syndrome (IBS), circulating leptin concentrations are reported to differ from those of healthy control subjects. Additionally, IBS patients display altered cytokine profiles, including elevated circulating concentrations of the pro-inflammatory cytokine interleukin-6 (IL-6), which bears structural homology and similarities in intracellular signalling to leptin. This study aimed to investigate interactions between leptin and IL-6 in colonic neurons and their possible contribution to IBS pathophysiology. The functional effects of leptin and IL-6 on colonic contractility and absorptosecretory function were assessed in organ baths and Ussing chambers in Sprague–Dawley rat colon. Calcium imaging and immunohistochemical techniques were used to investigate the neural regulation of GI function by these signalling molecules. Our findings provide a neuromodulatory role for leptin in submucosal neurons, where it inhibited the stimulatory effects of IL-6. Functionally, this translated to suppression of IL-6-evoked potentiation of veratridine-induced secretory currents. Leptin also attenuated IL-6-induced colonic contractions, although it had little direct effect on myenteric neurons. Calcium responses evoked by IBS plasma in both myenteric and submucosal neurons were also suppressed by leptin, possibly through interactions with IL-6, which is elevated in IBS plasma. As leptin has the capacity to ameliorate the neurostimulatory effects of soluble mediators in IBS plasma and modulated IL-6-evoked changes in bowel function, leptin may have a role in immune-mediated bowel dysfunction in IBS patients. en
dc.description.sponsorship Physiological Society, UK (R14920); University College Cork (College of Science, Engineering & Food Science) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Wiley en
dc.rights © 2016 The Authors. Experimental Physiology ©2016 The Physiological Society. This is the peer reviewed version of the following article: Buckley et al. (2016) 'Leptin modifies the prosecretory and prokinetic effects of the inflammatory cytokine interleukin-6 on colonic function in Sprague–Dawley rats', Experimental Physiology, 101(12), which has been published in final form at http://dx.doi.org/10.1113/EP085917. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms en
dc.subject Colonic contractility en
dc.subject Colonic secretion en
dc.subject Enteric neurons en
dc.subject Interleukin-6 en
dc.subject Leptin en
dc.title Leptin modifies the prosecretory and prokinetic effects of the inflammatory cytokine interleukin-6 on colonic function in Sprague–Dawley rats en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Dervla O'Malley, Physiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: d.omalley@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this item is restricted until 12 months after publication by the request of the publisher. en
dc.check.date 2017-09-27
dc.date.updated 2017-01-05T15:41:12Z
dc.description.version Accepted Version en
dc.internal.rssid 368395680
dc.internal.pmid 27676233
dc.contributor.funder Physiological Society en
dc.contributor.funder University College Cork en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Experimental Physiology en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress d.omalley@ucc.ie en


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