News Release

High protein diets point to new anti-obesity treatments

Peer-Reviewed Publication

Society for Endocrinology

A component of dietary protein, phenylalanine, can suppress appetite by affecting the release of appetite-regulating hormones in the gut, according to new research presented today at the Society for Endocrinology annual conference in Harrogate. The study shows how phenylalanine reduces food intake by affecting the gut and the brain, and suggests that it may be used to prevent or treat obesity.

Although high protein diets have been shown to be satisfying and to promote weight loss, they can be hard to maintain and may lead to other health problems in the long-term. Phenylalanine is an amino acid produced in the gut when protein is digested and has previously been shown to affect the release of gut hormones that reduce appetite in rodents. However, it was unclear exactly how the amino acid was causing this release and whether other systems were involved in phenylalanine's appetite supressing effects.

To investigate the effects of phenylalanine on appetite and gut hormone release, Professor Kevin Murphy and colleagues at Imperial College London, examined the effect of the amino acid on food intake and brain activity in areas known to be involved in appetite regulation. Mice were given phenylalanine, either orally or rectally, to assess the effects on different parts of the gut. Food intake was monitored at regular intervals over 24 hours and the amount of activity in brain areas associated with appetite regulation was also assessed. Both oral and rectal phenylalanine reduced food intake of the mice and increased activation in a brain area known to be involved in regulating appetite. After rectal administration, even an amount of phenylalanine 10 times lower than would be eaten daily on a high protein diet, resulted in reduced food intake and activated the appetite regulating centres in the brain.

These data suggest that phenylalanine may reduce appetite through different pathways in the upper and lower gut. Although unknown whether phenylalanine has the same effects on human appetite, this research indicates that the amino acid may have an important role in regulating food intake that could be used to treat obesity.

Mariana Norton, the PhD student who conducted the study, comments, "Understanding how food is detected in the gut may help to identify ways of treating or preventing obesity. The next step is to establish whether phenylalanine can drive similar appetite reducing effects in humans."

Ms Norton further states, "Diets high in protein are known to encourage weight loss but adhering to them can be difficult. Identifying the mechanisms that sense the protein may allow us to use drugs or functional foods to hijack appetite regulation, and treat obesity."




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, United Kingdom

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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