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https://hdl.handle.net/2440/117827
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Type: | Journal article |
Title: | Augmented capacity for peripheral serotonin release in human obesity |
Author: | Young, R. Lumsden, A. Martin, A. Schober, G. Pezos, N. Thazhath, S. Isaacs, N. Cvijanovic, N. Sun, E. Wu, T. Rayner, C. Nguyen, Q.N. Fontgalland, D. Rabbitt, P. Hollington, P. Sposato, L. Due, S. Wattchow, D. Liou, A. Jackson, V. et al. |
Citation: | International Journal of Obesity, 2018; 42(11):1880-1889 |
Publisher: | Macmillan Publishers |
Issue Date: | 2018 |
ISSN: | 0307-0565 1476-5497 |
Statement of Responsibility: | Richard L. Young … Nektaria Pezos … Nicole J. Isaacs … Nada Cvijanovic … Tongzhi Wu … Christopher K. Rayner … Nam Q. Nguyen … et al. |
Abstract: | Background/objectives: Evidence from animal studies highlights an important role for serotonin (5-HT), derived from gut enterochromaffin (EC) cells, in regulating hepatic glucose production, lipolysis and thermogenesis, and promoting obesity and dysglycemia. Evidence in humans is limited, although elevated plasma 5-HT concentrations are linked to obesity. Subjects/methods: We assessed (i) plasma 5-HT concentrations before and during intraduodenal glucose infusion (4 kcal/ min for 30 min) in non-diabetic obese (BMI 44 ± 4 kg/m2, N = 14) and control (BMI 24 ± 1 kg/m2, N = 10) subjects, (ii) functional activation of duodenal EC cells (immunodetection of phospho-extracellular related-kinase, pERK) in response to glucose, and in separate subjects, (iii) expression of tryptophan hydroxylase-1 (TPH1) in duodenum and colon (N = 39), and (iv) 5-HT content in primary EC cells from these regions (N = 85). Results Plasma 5-HT was twofold higher in obese than control responders prior to (P = 0.025), and during (iAUC, P = 0.009), intraduodenal glucose infusion, and related positively to BMI (R2 = 0.334, P = 0.003) and HbA1c (R2 = 0.508, P = 0.009). The density of EC cells in the duodenum was twofold higher at baseline in obese subjects than controls (P = 0.023), with twofold more EC cells activated by glucose infusion in the obese (EC cells co-expressing 5-HT and pERK, P = 0.001), while the 5-HT content of EC cells in duodenum and colon was similar; TPH1 expression was 1.4-fold higher in the duodenum of obese subjects (P = 0.044), and related positively to BMI (R2 = 0.310, P = 0.031). Conclusions: Human obesity is characterized by an increased capacity to produce and release 5-HT from the proximal small intestine, which is strongly linked to higher body mass, and glycemic control. Gut-derived 5-HT is likely to be an important driver of pathogenesis in human obesity and dysglycemia. Introduction |
Keywords: | Colon Enterochromaffin Cells Peripheral Nervous System Cells, Cultured Humans Obesity Serotonin Blood Glucose Endoscopy, Gastrointestinal Signal Transduction Adult Middle Aged Female Male Real-Time Polymerase Chain Reaction |
Rights: | © Macmillan Publishers Limited, part of Springer Nature 2018. |
DOI: | 10.1038/s41366-018-0047-8 |
Grant ID: | http://purl.org/au-research/grants/arc/LP150100419 |
Published version: | http://dx.doi.org/10.1038/s41366-018-0047-8 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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