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

Diabetes Obes Metab. 2016 May;18(5):508-18. doi: 10.1111/dom.12644. Epub 2016 Apr 1.

Abstract

Aims: To investigate the anorectic effect of L-arginine (L-Arg) in rodents.

Methods: We 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.

Results: Oral 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.

Keywords: GLP-1; animal pharmacology; body composition; energy regulation; obesity therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite Depressants / administration & dosage
  • Appetite Depressants / adverse effects
  • Appetite Depressants / pharmacology
  • Appetite Depressants / therapeutic use*
  • Arginine / administration & dosage
  • Arginine / adverse effects
  • Arginine / therapeutic use*
  • Cells, Cultured
  • Dietary Supplements* / adverse effects
  • Energy Intake / drug effects
  • Energy Metabolism / drug effects
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / pharmacology
  • Gastrointestinal Agents / therapeutic use*
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism
  • In Vitro Techniques
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / diet therapy*
  • Obesity / drug therapy
  • Obesity / metabolism
  • Obesity / pathology
  • Peptide YY / agonists*
  • Peptide YY / blood
  • Peptide YY / metabolism
  • Random Allocation
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Weight Loss / drug effects

Substances

  • Appetite Depressants
  • GPRC6A protein, mouse
  • Gastrointestinal Agents
  • Receptors, G-Protein-Coupled
  • Peptide YY
  • Glucagon-Like Peptide 1
  • Arginine