Endocrine Abstracts (2017) 50 P321 | DOI: 10.1530/endoabs.50.P321

Rectal and oral administration of L-Phenylalanine supresses food intake and modulates neuronal activation in appetite-regulating brain regions in rodents

Mariana Norton, Ye Cao, Risha Amarsi, Isabel Fernandes Freitas, Amin Alamshah & Kevin G Murphy


Imperial College, London, UK.


High protein diets are highly satiating but hard to maintain. By understanding the mechanisms underlying these effects we may be able to identify new anti-obesity therapies. Protein is broken-down into amino acids in the gut which are detected by a series of nutrient sensors. The calcium sensing receptor (CaSR) is primarily activated by calcium ions, but is positively allosterically modulated by aromatic amino acids, especially L-phenylalanine. Stimulation of the CaSR by L-phenylalanine can stimulate glucagon-like peptide-1 (GLP-1) secretion, but its role in the secretion of other gut hormones is unclear.

Studies in our department have shown that oral administration of L-phenylalanine suppresses food intake in rodents. We therefore aimed to investigate the mechanisms underlying these effects and which region of the gut is involved.

We examined the effect of orally and rectally administered L-phenylalanine on food intake and neuronal activation in mice. To investigate whether L-phenylalanine might be being systemically absorbed to have a direct effect on neuronal activation, we also investigated CaSR expression in the brain regions activated in response to L-phenylalanine.

In vivo, oral and rectal administration of L-phenylalanine reduced food intake and increased neuronal activation in the area postrema of mice. Immunohistological staining showed that the CaSR is expressed in the area postrema of mice. Mice orally administered L-phenylalanine also had significantly lower gastric inhibitory peptide (GIP) plasma levels.

Previous work suggests that oral L-phenylalanine can increase GLP-1 secretion and improve glucose tolerance, so the inhibitory effect of L-phenylalanine on GIP was unexpected. Further work is required to determine the role of the CaSR and L-phenylalanine in glucose homeostasis. In addition, the role of central nervous system amino acid sensing via the CaSR in the anorectic effects of L-phenylalanine requires further investigation.

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