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



Wolnerhanssen, BK, Moran, AW ORCID: 0000-0003-0031-2154, Burdyga, G, Meyer-Gerspach, AC, Peterli, R, Manz, M, Thumshirn, M, Daly, K ORCID: 0000-0002-1075-1831, Beglinger, C and Shirazi-Beechey, SP
(2017) Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals. Scientific Reports, 7 (1). 8174-.

Access the full-text of this item by clicking on the Open Access link.
[thumbnail of Scientific Reports 2017.pdf] Text
Scientific Reports 2017.pdf - Author Accepted Manuscript

Download (2MB)

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.

Item Type: Article
Uncontrolled Keywords: Intestinal Mucosa, Duodenum, Epithelial Cells, Humans, Obesity, Morbid, Gastrointestinal Hormones, Transcription Factors, Body Mass Index, Immunohistochemistry, Cell Differentiation, Gene Expression, Gene Expression Regulation, Adult, Female, Male, Enteroendocrine Cells, Chromogranin A, Biomarkers
Depositing User: Symplectic Admin
Date Deposited: 13 Jul 2017 10:56
Last Modified: 19 Jan 2023 06:59
DOI: 10.1038/s41598-017-08487-9
Open Access URL: https://www.nature.com/articles/s41598-017-08487-9
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3008443