Noncaloric Sweeteners Induce Peripheral Serotonin Secretion via the T1R3-Dependent Pathway in Human Gastric Parietal Tumor Cells (HGT-1).

Abstract

The role of sweet taste in energy intake and satiety regulation is still controversial. Noncaloric artificial sweeteners (NCSs) are thought to help reduce energy intake, although little is known about their impact on the satiating neurotransmitter serotonin (5-HT). In the gastrointestinal (GI) tract, 5-HT regulates gastric acid secretion and gastric motility, both part of the complex network of mechanisms regulating food intake and satiety. This study demonstrated a stimulating impact compared to controls (100%) on 5-HT release in human gastric tumor cells (HGT-1) by the NCSs cyclamate (50 mM, 157% ± 6.3%), acesulfame potassium (Ace K, 50 mM, 197% ± 8.6%), saccharin (50 mM, 147% ± 6.7%), sucralose (50 mM, 194% ± 11%), and neohesperidin dihydrochalcone (NHDC, 1 mM, 201% ± 13%). Although these effects were not associated with the sweet taste intensity of the NCSs tested, involvement of the sweet receptor subunit T1R3 in the NCS-evoked response was demonstrated by mRNA expression of TAS1R3, co-incubation experiments using the T1R3 receptor antagonist lactisole, and a TAS1R3 siRNA knockdown approach. Analysis of the downstream signaling revealed activation of the cAMP/ERK/Ca2+ cascade. Co-treatment experiments with 10 mM glucose enhanced the 5-HT release induced by cyclamate, Ace K, saccharin, and sucralose, thereby supporting the enhancing effect of glucose on a NCS-mediated response. Overall, the results obtained identify NCSs as potent inducers of 5-HT release via T1R3 in human gastric parietal cells in culture and warrant in vivo studies to demonstrate their efficacy.

• Authors: Muhammet Zopun, Barbara Lieder, Ann-Katrin Holik, Jakop P Ley, Joachim Hans, Veronika Somoza
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 66 Issue 27 Pg. 7044-7053 (Jul 11 2018) ISSN: 1520-5118 [Electronic] United States
• PMID: 29874909 (Publication Type: Journal Article)

Chemical References

• Benzene Derivatives
• Chalcones
• Cyclamates
• Receptors, G-Protein-Coupled
• Sweetening Agents
• Thiazines
• taste receptors, type 1
• Serotonin
• neohesperidin dihydrochalcone
• Cyclic AMP
• Hesperidin
• Saccharin
• acetosulfame
• lactisole

Topics

• Benzene Derivatives (pharmacology)
• Cell Line, Tumor
• Chalcones (pharmacology)
• Cyclamates (pharmacology)
• Cyclic AMP (metabolism)
• Gene Expression Regulation (drug effects)
• Hesperidin (analogs & derivatives, pharmacology)
• Humans
• Parietal Cells, Gastric (drug effects, metabolism, pathology)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Saccharin (pharmacology)
• Serotonin (metabolism)
• Signal Transduction (drug effects)
• Stomach Neoplasms (metabolism, pathology)
• Sweetening Agents (pharmacology)
• Thiazines (pharmacology)