SFEBES2016 Poster Presentations Obesity and Metabolism (26 abstracts)
L-Phenylalanine modulates gut hormone release, and suppresses food intake in rodents via the Calcium Sensing Receptor
Mariana Norton , Amin Alamshah , Eleanor Spreckley , James S. Kinsey-Jones , Anjali Amin , Fanyi Li , Ishani Canisius , Rebecca Johnson , Elina Akalestou , Zainab Malik , Stephen R. Bloom & Kevin G. Murphy
Imperial College London, London, UK.
High protein diets suppress appetite, but are difficult to adhere to. Understanding how the gut senses protein may identify mechanisms to drive satiety. Amino acid products of protein digestion are thought to be sensed by G protein coupled receptors in the gut, including the calcium sensing receptor (CaSR). Calcium ions are the major ligand of the CaSR, but aromatic amino acids, particularly L-phenylalanine (L-Phe), allosterically modulate CaSR activity.
Our pilot studies suggested oral administration of L-Phe could reduce food intake in rodents. We therefore aimed to investigate the mechanisms that may underlie these anorectic effect of L-Phe.
We examined the effect of L-Phe on food intake, energy expenditure, behaviour, gut hormone secretion and neuronal activation, in rodents. Additionally, we explored the role of the CaSR in mediating gut hormone secretion in vitro and food intake in vivo.
In vitro, L-Phe stimulated secretion of the anorectic gut hormone glucagon-like peptide-1 (GLP-1) from STC-1 cells, an effect attenuated by CaSR antagonist. In vivo, orally administered L-Phe reduced food intake, increased circulating levels of GLP-1, supressed circulating levels of the orexigenic gastric hormone ghrelin, increased locomotor behaviour, and modulated neuronal activity in appetite regulating centres of the brain. Intra-ileal administration of L-Phe in rats supressed food intake, and this effect was attenuated by CaSR antagonist. Chronically, L-Phe decreased food intake and body weight in diet induced obese mice.
Further work is required to confirm whether the effects of L-Phe on gut hormone release mediate its effects on food intake and neuronal activation. L-Phe and the CaSR may represent new therapeutic targets for functional foods or drugs designed to regulate appetite and body weight.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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