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.
Highlights
Obesity and its associated conditions, such as type-2 diabetes and cardiovascular disease, are major health threats worldwide
We first confirmed that there is a significant increase in postprandial GLP-1, peptide YY (PYY) and CCK release in a cohort of morbidly obese subjects 3 months post laparoscopic sleeve gastrectomy (LSG) compared to that in the same individuals, pre LSG
We show some enteroendocrine cells (EEC) in human duodenum express GLP-1 and GLP-2, as expected, the number of GLP-1 and GLP-2 expressing EECs are significantly lower than those expressing CCK or PYY
Summary
Obesity and its associated conditions, such as type-2 diabetes and cardiovascular disease, are major health threats worldwide. The intestinal epithelium is a site of satiation signal generation, where specialized enteroendocrine (sensor) cells (EECs) respond to nutrients by releasing hormones that control energy homeostasis, food intake and insulin secretion[1, 2]. Ghrelin is released by enteroendocrine X/A cells of the stomach, and by open-type EECs of the duodenum, acting as an orexigenic hormone, stimulating appetite and food intake[11,12,13]. Absorptive enterocytes, mucus-producing goblet cells and Paneth cells are the other epithelial cells lining the intestine. Goblet cells are the most copious secretory lineage of the intestinal epithelia, comprising up to 10% of small intestinal epithelial cells[16] They produce and secrete mucus to provide epithelial cells a protective shield against noxious luminal contents. Paneth cells produce antimicrobial peptides such as defensins that are secreted into the lumen of the intestine[17]
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