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L-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium sensing receptor in rodents

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Title: L-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium sensing receptor in rodents
Authors: Murphy, KG
Spreckley, E
Norton, M
Kinsey-Jones, J
Amin, A
Ramgulam, A
Cao, Y
Johnson, R
Saleh, K
Jomard, A
Amarsi, R
Moolla, A
Akalestou, E
Malik, Z
Gonzalez Abuin
Sargent, P
Gray, G
Bloom, S
Item Type: Journal Article
Abstract: Objectives: High protein diets are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which high protein diets exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may play a role in appetite regulation and satiety. We investigated the effects of L-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. Methods: We investigated the effects of the aromatic amino acid and calcium sensing receptor (CaSR) agonist L-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo. We also examined the effect of oral L-Phe administration on glucose tolerance in rats. Results: Oral administration of L-Phe acutely reduced food intake in rats and mice, and chronically reduced food intake and body weight in diet-induced obese mice. Ileal L-Phe also reduced food intake in rats. L-Phe stimulated GLP-1 and PYY release, and reduced plasma ghrelin, and also stimulated insulin release and improved glucose tolerance in rats. Pharmacological blockade of the CaSR attenuated the anorectic effect of intra-ileal L-Phe in rats, and L-Phe-induced GLP-1 release from STC-1 and primary L cells was attenuated by CaSR blockade. Conclusions: L-Phe reduced food intake, stimulated GLP-1 and PYY release and reduced plasma ghrelin in rodents. Our data provides evidence that the anorectic effects of L-Phe are mediated via the CaSR, and suggest that L-Phe and the CaSR system in the gastrointestinal tract may have therapeutic utility in the treatment of obesity and diabetes. Further work is required to determine the physiological role of the CaSR in protein sensing in the gut, and the role of this system in humans.
Issue Date: 13-Jul-2017
Date of Acceptance: 22-Jun-2017
URI: http://hdl.handle.net/10044/1/49671
DOI: https://dx.doi.org/10.1038/ijo.2017.164
ISSN: 1476-5497
Publisher: Nature Publishing Group
Start Page: 1693
End Page: 1701
Journal / Book Title: International Journal of Obesity
Volume: 41
Copyright Statement: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article ’ s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0/
Sponsor/Funder: Medical Research Council (MRC)
Innovate UK
Funder's Grant Number: MR/J010944/1
Keywords: 11 Medical And Health Sciences
13 Education
Endocrinology & Metabolism
Publication Status: Published
Appears in Collections:Department of Medicine (up to 2019)