Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals

Abstract Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidl...

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Autores principales:	Bettina K. Wölnerhanssen, Andrew W. Moran, Galina Burdyga, Anne Christin Meyer-Gerspach, Ralph Peterli, Michael Manz, Miriam Thumshirn, Kristian Daly, Christoph Beglinger, Soraya P. Shirazi-Beechey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19e2aa8c8d79464db6ccd45fe1ba5b5e
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spelling	oai:doaj.org-article:19e2aa8c8d79464db6ccd45fe1ba5b5e2021-12-02T15:06:04ZDeregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals10.1038/s41598-017-08487-92045-2322https://doaj.org/article/19e2aa8c8d79464db6ccd45fe1ba5b5e2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08487-9https://doaj.org/toc/2045-2322Abstract Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na+/glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.Bettina K. WölnerhanssenAndrew W. MoranGalina BurdygaAnne Christin Meyer-GerspachRalph PeterliMichael ManzMiriam ThumshirnKristian DalyChristoph BeglingerSoraya P. Shirazi-BeecheyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bettina K. Wölnerhanssen Andrew W. Moran Galina Burdyga Anne Christin Meyer-Gerspach Ralph Peterli Michael Manz Miriam Thumshirn Kristian Daly Christoph Beglinger Soraya P. Shirazi-Beechey Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals
description	Abstract Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na+/glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.
format	article
author	Bettina K. Wölnerhanssen Andrew W. Moran Galina Burdyga Anne Christin Meyer-Gerspach Ralph Peterli Michael Manz Miriam Thumshirn Kristian Daly Christoph Beglinger Soraya P. Shirazi-Beechey
author_facet	Bettina K. Wölnerhanssen Andrew W. Moran Galina Burdyga Anne Christin Meyer-Gerspach Ralph Peterli Michael Manz Miriam Thumshirn Kristian Daly Christoph Beglinger Soraya P. Shirazi-Beechey
author_sort	Bettina K. Wölnerhanssen
title	Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals
title_short	Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals
title_full	Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals
title_fullStr	Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals
title_full_unstemmed	Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals
title_sort	deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/19e2aa8c8d79464db6ccd45fe1ba5b5e
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Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals

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