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https://hdl.handle.net/2440/117827
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dc.contributor.author | Young, R. | - |
dc.contributor.author | Lumsden, A. | - |
dc.contributor.author | Martin, A. | - |
dc.contributor.author | Schober, G. | - |
dc.contributor.author | Pezos, N. | - |
dc.contributor.author | Thazhath, S. | - |
dc.contributor.author | Isaacs, N. | - |
dc.contributor.author | Cvijanovic, N. | - |
dc.contributor.author | Sun, E. | - |
dc.contributor.author | Wu, T. | - |
dc.contributor.author | Rayner, C. | - |
dc.contributor.author | Nguyen, Q.N. | - |
dc.contributor.author | Fontgalland, D. | - |
dc.contributor.author | Rabbitt, P. | - |
dc.contributor.author | Hollington, P. | - |
dc.contributor.author | Sposato, L. | - |
dc.contributor.author | Due, S. | - |
dc.contributor.author | Wattchow, D. | - |
dc.contributor.author | Liou, A. | - |
dc.contributor.author | Jackson, V. | - |
dc.contributor.author | et al. | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | International Journal of Obesity, 2018; 42(11):1880-1889 | - |
dc.identifier.issn | 0307-0565 | - |
dc.identifier.issn | 1476-5497 | - |
dc.identifier.uri | http://hdl.handle.net/2440/117827 | - |
dc.description.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 | - |
dc.description.statementofresponsibility | Richard L. Young … Nektaria Pezos … Nicole J. Isaacs … Nada Cvijanovic … Tongzhi Wu … Christopher K. Rayner … Nam Q. Nguyen … et al. | - |
dc.language.iso | en | - |
dc.publisher | Macmillan Publishers | - |
dc.rights | © Macmillan Publishers Limited, part of Springer Nature 2018. | - |
dc.source.uri | http://dx.doi.org/10.1038/s41366-018-0047-8 | - |
dc.subject | Colon | - |
dc.subject | Enterochromaffin Cells | - |
dc.subject | Peripheral Nervous System | - |
dc.subject | Cells, Cultured | - |
dc.subject | Humans | - |
dc.subject | Obesity | - |
dc.subject | Serotonin | - |
dc.subject | Blood Glucose | - |
dc.subject | Endoscopy, Gastrointestinal | - |
dc.subject | Signal Transduction | - |
dc.subject | Adult | - |
dc.subject | Middle Aged | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.subject | Real-Time Polymerase Chain Reaction | - |
dc.title | Augmented capacity for peripheral serotonin release in human obesity | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/s41366-018-0047-8 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/LP150100419 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Young, R. [0000-0001-5116-4951] [0009-0004-8274-9863] | - |
dc.identifier.orcid | Cvijanovic, N. [0000-0002-4473-452X] | - |
dc.identifier.orcid | Wu, T. [0000-0003-1656-9210] | - |
dc.identifier.orcid | Rayner, C. [0000-0002-5527-256X] | - |
dc.identifier.orcid | Nguyen, Q.N. [0000-0002-1270-5441] | - |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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