Recombinant incretin-secreting microbe improves metabolic dysfunction in high-fat diet fed rodents

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dc.contributor.author Ryan, Paul M.
dc.contributor.author Patterson, Elaine
dc.contributor.author Kent, Robert M.
dc.contributor.author Stack, Helena
dc.contributor.author O'Connor, Paula M.
dc.contributor.author Murphy, Kiera
dc.contributor.author Peterson, Veronica L.
dc.contributor.author Mandal, Rupasri
dc.contributor.author Wishart, David S.
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Cryan, John F.
dc.contributor.author Seeley, Randy J.
dc.contributor.author Stanton, Catherine
dc.contributor.author Ross, R. Paul
dc.date.accessioned 2018-02-06T13:36:27Z
dc.date.available 2018-02-06T13:36:27Z
dc.date.issued 2017
dc.identifier.citation Ryan, P. M., Patterson, E., Kent, R. M., Stack, H., O’Connor, P. M., Murphy, K., Peterson, V. L., Mandal, R., Wishart, D. S., Dinan, T. G., Cryan, J. F., Seeley, R. J., Stanton, C. and Ross, R. P. (2017) 'Recombinant incretin-secreting microbe improves metabolic dysfunction in high-fat diet fed rodents', Scientific Reports, 7(1), 13523 (12pp). doi: 10.1038/s41598-017-14010-x en
dc.identifier.volume 7
dc.identifier.startpage 1
dc.identifier.endpage 12
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10468/5382
dc.identifier.doi 10.1038/s41598-017-14010-x
dc.description.abstract The gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction. en
dc.description.sponsorship Teagasc (Walsh Fellow Short-term Overseas Training Award) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Nature Publishing Group en
dc.relation.uri https://www.nature.com/articles/s41598-017-14010-x
dc.rights © 2017, the authors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject Glucagon-like peptide-1 en
dc.subject Type-2 diabetes-mellitus en
dc.subject Gut microbiota en
dc.subject Lactococcus-lactis en
dc.subject Lipid-metabolism en
dc.subject Healthy humans en
dc.subject Bacteria en
dc.subject Exenatide en
dc.subject GLP-1 en
dc.subject Elevations en
dc.title Recombinant incretin-secreting microbe improves metabolic dysfunction in high-fat diet fed rodents en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother p.ross@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000413190900002
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder Ireland Canada University Foundation
dc.contributor.funder Teagasc
dc.description.status Peer reviewed en
dc.identifier.journaltitle Scientific Reports en
dc.internal.IRISemailaddress Paul Ross, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. +353-21-490-3000 E-mail:paul.ross@teagasc.ie en
dc.identifier.articleid 13523
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/


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© 2017, the authors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Except where otherwise noted, this item's license is described as © 2017, the authors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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