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.

Patients with NFPAs without optic chiasm compression can be managed conservatively. All patients need pituitary function assessment, irrespective of tumour size. These findings provide clinically relevant data for the management of patients with NFPAs.

Aims The effect of atrial fibrillation catheter ablation on cardiovascular outcomes in heart failure is an important outstanding research question. We undertook a meta-analysis of randomized controlled trials comparing ablation to medical therapy in patients with AF and heart failure. Methods and results We systematically identified all trials comparing catheter ablation to medical therapy in patients with heart failure and atrial fibrillation. The pre-specified primary endpoint was all-cause mortality in trials with at least 2 years of follow-up. The secondary endpoint was heart failure hospitalization. Sensitivity analyses were performed for trials with any follow-up and trials deemed at low risk of bias. Eight trials (1390 patients) were included. Seven hundred and seven patients were randomized to catheter ablation and 683 to medical therapy. In the primary analysis (three trials, n = 977), catheter ablation reduced mortality compared with medical therapy [relative risk (RR): 0.61, 95% confidence interval (CI): 0.44 to 0.84, P = 0.003]. Catheter ablation also reduced heart failure hospitalizations compared with medical therapy (RR: 0.60, 95% CI: 0.49–0.74, P < 0.001). The effect on stroke was not statistically significant (RR: 0.62, 95% CI: 0.28–1.37, P = 0.237). There was low heterogeneity between studies. Sensitivity analyses were consistent with the primary analyses. Conclusion In patients with atrial fibrillation and heart failure, catheter ablation reduces mortality and the occurrence of heart failure hospitalizations.