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

Scientific Reports - Tập 7 Số 1
Bettina K. Wölnerhanssen1, Andrew W. Moran2, Galina Burdyga2, Anne Christin Meyer‐Gerspach3, Ralph Peterli4, Markus G. Manz5, Miriam Thumshirn5, Kristian Daly2, Christoph Beglinger6, Soraya P. Shirazi‐Beechey2
1Department of Clinical Research, St. Claraspital Basel, 4058, Basel, Switzerland
2Institute of Integrative Biology, University of Liverpool, Liverpool, Merseyside, L69 7ZB, United Kingdom
3Department of Biomedicine, University Hospital Basel, 4056, Basel, Switzerland
4Department of Surgery, St. Claraspital Basel, 4058, Basel, Switzerland
5Department of Gastroenterology, St. Claraspital Basel, 4058, Basel, Switzerland
6Department of Gastroenterology, University Hospital Basel, 4056, Basel, Switzerland

Tóm tắt

AbstractMorbidly 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.

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