AUTHOR=Franco Claudinéia Conationi da Silva, Previate Carina, Trombini Amanda Bianchi, Miranda Rosiane Aparecida, Barella Luiz Felipe, Saavedra Lucas Paulo Jacinto, de Oliveira Júlio Cezar, Prates Kelly Valério, Tófolo Laize Peron, Ribeiro Tatiane Aparecida, Pavanello Audrei, Malta Ananda, Martins Isabela Peixoto, Moreira Veridiana Motta, Matiusso Camila Cristina Ianoni, Francisco Flávio Andrade, Alves Vander Silva, de Moraes Ana Maria Praxedes, de Sant Anna Juliane Rocha, de Castro Prado Marialba Avezum Alves, Gomes Rodrigo Mello, Vieira Elaine, de Freitas Mathias Paulo Cezar TITLE=Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats JOURNAL=Frontiers in Endocrinology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/articles/10.3389/fendo.2021.660793 DOI=10.3389/fendo.2021.660793 ISSN=1664-2392 ABSTRACT=Metformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). During 21–100 days of age, MSG-rats were treated with metformin 250 mg/kg body weight/day or saline solution. Rats were euthanized to evaluate biometric and biochemical parameters. ANS electrical activity was recorded and analyzed. Metformin normalized the hypervagal response in MSG-rats. Glucose-stimulated insulin secretion in isolated pancreatic islets increased in MSG-rats, while the cholinergic response decreased. Metformin treatment normalized the cholinergic response, which involved mostly the M3 muscarinic acetylcholine receptor (M3 mAChR) in pancreatic beta-cells. Protein expression of M3 mAChRs increased in MSG-obesity rats, while metformin treatment decreased the protein expression by 25%. In conclusion, chronic metformin treatment was effective in normalizing ANS activity and alleviating obesity in MSG-rats.