title: Oxytocin treatment prevents the cardiomyopathy observed in obese diabetic male db/db mice.
abstract: Oxytocin (OT) is involved in the regulation of energy metabolism and in the activation of cardioprotective mechanisms. We evaluated whether chronic treatment with OT could prevent the metabolic and cardiac abnormalities associated with diabetes and obesity using the db/db mice model. Four-week-old male db/db mice and their lean nondiabetic littermates (db/+) serving as controls were treated with OT (125 ng/kg · h) or saline vehicle for a period of 12 weeks. Compared with db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia, and hyperinsulinemia. These mice also exhibited a deficient cardiac OT/natriuretic system and developed systolic and diastolic dysfunction resulting from cardiomyocyte hypertrophy, fibrosis, and apoptosis. These abnormalities were associated with increased reactive oxygen species (ROS) production, inflammation, and suppressed 5'-adenosine monophosphate kinase signaling pathway. The db/db mice displayed reduced serum levels of adiponectin and adipsin and elevated resistin. OT treatment increased circulating OT levels, significantly reduced serum resistin, body fat accumulation (19%; P<.001), fasting blood glucose levels by (23%; P<.001), and improved glucose tolerance and insulin sensitivity. OT also normalized cardiac OT receptors, atrial natriuretic peptide, and brain natriuretic peptide, expressions and prevented systolic and diastolic dysfunction as well as cardiomyocyte hypertrophy, fibrosis, and apoptosis. Furthermore, OT reduced cardiac oxidative stress and inflammation and normalized the 5'-adenosine monophosphate-activated protein kinase signaling pathway. The complete normalization of cardiac structure and function by OT treatment in db/db mice contrasted with only partial improvement of hyperglycemia and hyperinsulinemia. These results indicate that chronic treatment with OT partially improves glucose and fat metabolism and reverses abnormal cardiac structural remodeling, preventing cardiac dysfunction in db/db mice.
authors.affiliation: Cardiovascular Biochemistry Laboratory (E.P., A.M., B.A.D., D.Y., M.J., J.G.), Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Canada H2X 0A9; Department of Medicine (E.P., J.-L.C., M.J., J.G.), Québec, Canada H3T 1J4; and Department of Physiology (T.L.B.), Midwestern University, Glendale, Arizona 85308.
authors.forename: Eric
authors.initials: E
authors.lastname: Plante
authors.forename: Ahmed
authors.initials: A
authors.lastname: Menaouar
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Danalache
authors.forename: Denis
authors.initials: D
authors.lastname: Yip
authors.forename: Tom L
authors.initials: TL
authors.lastname: Broderick
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Chiasson
authors.forename: Marek
authors.initials: M
authors.lastname: Jankowski
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D006946:Hyperinsulinism / Q000150:complications* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology / Q000627:therapeutic use*; D052243:Resistin / Q000097:blood
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D052243:Resistin; D010121:Oxytocin