Abstract
Objective:High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have 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 (GI) 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 provide evidence that the anorectic effects of l-Phe are mediated via the CaSR, and suggest that l-Phe and the CaSR system in the GI 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.
Highlights
Obesity is a major health problem associated with serious comorbidities, including type II diabetes.[1,2] Diet and life style modifications are often difficult to adhere to and ineffective over long periods
The expression of the promiscuous amino-acid-sensing receptors, the umami taste receptor T1R1/T1R3, the G-protein-coupled receptor family C group 6 member A and the calcium-sensing receptor (CaSR)[5,6] in the gastrointestinal (GI) tract has led to the suggestion that they may sense to the amino-acid products of protein digestion to mediate satiety.[6]
Both glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are highly expressed in the ileum, and the ileum may have a role in the greater satiety observed following a high-protein meal
Summary
High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. Evidence suggests that the sensing of amino acids produced as a result of protein digestion may have 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 (GI) 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. L-Phe stimulated GLP-1 and PYY release, and reduced plasma ghrelin, and stimulated insulin release and improved glucose tolerance in rats. CONCLUSIONS: L-Phe reduced food intake, stimulated GLP-1 and PYY release, and reduced plasma ghrelin in rodents. 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
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