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=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/endocrinology/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. Autonomic nervous system (ANS) imbalance is associated with metabolic diseases. The aim this study was to test whether metformin could improve ANS activity in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). From twenty-one-day-old to 100-day-old, MSG-rats were treated with metformin 250 mg/kg body weight/day, or saline. Rats were euthanized to biometric and biochemical parameters evaluation. ANS electrical activity was recorded. Metformin normalized the hyper vagal response in MSG-rats. Insulin secretion stimulated by glucose in isolated islets was increased in MSG rats, while, cholinergic response was reduced. Metformin treatment normalized the cholinergic response, which involved mostly the pancreatic beta cell muscarinic receptor type M3mAChR. Protein expression of muscarinic receptors M3mAChR was increased in MSG-obesity rats; while metformin treatment decreased the expression by 25%. In conclusion chronic metformin treatment was effective to normalized ANS activity and alleviating obesity in MSG-rats.