L-arginine promotes gut hormone release and reduces food intake in rodents.

A Alamshah,K G Murphy,S R Bloom,G Hyberg,I R Tough,A Moolla,R France,A K Mcgavigan,E Spreckley,A Lehmann,A Amin,H M Cox,M Norton,J S Kinsey‐Jones,H C O'Hara,K Banks,W Cheong

doi:10.1111/dom.12644

Abstract

AimsTo investigate the anorectic effect of L‐arginine (L‐Arg) in rodents.MethodsWe investigated the effects of L‐Arg on food intake, and the role of the anorectic gut hormones glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY), the G‐protein‐coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents.ResultsOral gavage of L‐Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet‐induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L‐Arg stimulated GLP‐1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP‐1 and PYY receptors did not influence the anorectic effect of L‐Arg. L‐Arg‐mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L‐Arg suppressed food intake in rats.Conclusions L‐Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L‐Arg is unlikely to be mediated by GLP‐1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L‐Arg suppressed food intake in rats, suggesting that L‐Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L‐Arg suppresses food intake and its utility in the treatment of obesity.

Highlights

High protein diets promote satiety and weight loss [1,2], but the exact mechanisms mediating these effects are unclear
After observing that L-Arg administration could result in a sustained reduction in food intake in rodents, we investigated whether this anorectic effect could be sustained chronically and reduce body weight in a diet-induced obese (DIO) mouse model, a commonly used model of obesity
Repeated L-Arg administration significantly reduced food intake on day 1 and day 2 in DIO mice compared with vehicle-treated mice (Figure 1F), this effect was insufficient to significantly change body weight over the time period studied (Figure 1G)

Summary

Introduction

High protein diets promote satiety and weight loss [1,2], but the exact mechanisms mediating these effects are unclear. Mechanisms proposed to mediate the effects of high protein diets on food intake, include increased thermogenesis, intestinal gluconeogenesis and changes in gut hormone profiles [4]. Such mechanisms may be instigated by the sensing of the amino acids produced by protein digestion. Rodents adapt their diet to balance amino acid intake [5]. The recent discovery of promiscuous L-amino acid-sensing G-protein-coupled receptors and their expression in the gastrointestinal tract has

Methods

Results

Conclusion