Oral Presentation ANZOS-OSSANZ-AOCO Joint Annual Scientific Meeting 2017

Augmented capacity for intestinal serotonin release in obese subjects  (#89)

Amanda Lumsden 1 , Alyce M Martin 1 , Nektaria Pezos 2 3 , Sony S Thazhath 2 4 , Nicole J Isaacs 2 3 , Nada Cvijanovic 2 3 , Emily WL Sun 1 , Tongzhi Wu 2 4 , Chris K Rayner 2 4 , Nam Q Nguyen 2 4 , Dayan de Fontgalland 5 , Philippa Rabbitt 5 , Paul Hollington 5 , Luigi Sposato 5 , Steven L Due 5 , David A Wattchow 5 , Alice Liou 6 , V Margaret Jackson 6 , Damien J Keating 1 3 , Richard L Young 2 3 4
  1. Department of Human Physiology, Flinders University, Bedford Park, SA, AUSTRALIA
  2. Adelaide Medical School, University of Adelaide, Adelaide, SA, AUSTRALIA
  3. Nutrition & Metabolism Theme , South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AUSTRALIA
  4. NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, AUSTRALIA
  5. Department of Surgery, Flinders Medical Centre, Bedford Park, SA, AUSTRALIA
  6. Cardiovascular and Metabolic Diseases Unit, Pfizer Inc., Boston, MA, USA

Recent evidence from animal studies supports a role for serotonin (5-HT), derived from gut enterochromaffin (EC) cells, in regulating hepatic glucose production, lipolysis and thermogenesis. Evidence in humans is limited, although elevated plasma 5-HT concentrations have been linked to obesity.

We assessed (i) plasma 5-HT concentrations before and during intraduodenal glucose infusion (4 kcal/min for 30 min) in obese non-diabetic (BMI 44 ± 4 kg/m2, N=14) and control (BMI 24 ± 1 kg/m2, N=10) subjects, (ii) functional activation of duodenal EC cells (co-immunodetection of phospho-extracellular related kinase, pERK) in response to glucose, and in separate subjects, (iii) expression of TPH1 (encoding tryptophan hydroxylase-1, the rate limiting enzyme in 5-HT synthesis), in duodenum and colon (N=39), and (iv) 5-HT content and glucose responses of primary EC cells isolated from these regions (N=85).

Plasma 5-HT was positively related to BMI in fasted obese and control subjects (P ≤ 0.05), and was higher in obese than controls before (1.7-fold, P ≤ 0.05), and during (2.7-fold iAUC, P ≤ 0.01) intraduodenal glucose infusion. Duodenal EC cell density was two-fold greater in obese than controls (P ≤ 0.01), while the proportion showing glucose-dependent activation (pERK labelling), and the 5-HT content of duodenal and colonic EC cells, were similar. TPH1 expression was similar in duodenum and colon in control subjects, but 40% higher in the duodenum of obese subjects (P ≤ 0.05), with expression correlating positively to BMI (P ≤ 0.001). Examination of the nutrient responsiveness of human EC cells demonstrates that duodenal and colonic EC cells respond to glucose but not fructose.

Obese subjects have increased capacity to produce 5‑HT in the proximal small intestine, and augmented glucose-stimulated 5-HT release. Gut-derived 5-HT is potentially important in the pathogenesis of obesity.