title: Divergent effects of oxytocin treatment of obese diabetic mice on adiposity and diabetes.
abstract: Oxytocin has been suggested as a novel therapeutic against obesity, because it induces weight loss and improves glucose tolerance in diet-induced obese rodents. A recent clinical pilot study confirmed the oxytocin-induced weight-reducing effect in obese nondiabetic subjects. Nevertheless, the mechanisms involved and the impact on the main comorbidity associated with obesity, type 2 diabetes, are unknown. Lean and ob/ob mice (model of obesity, hyperinsulinemia, and diabetes) were treated for 2 weeks with different doses of oxytocin, analogues with longer half-life (carbetocin) or higher oxytocin receptor specificity ([Thr4,Gly7]-oxytocin). Food and water intake, body weight, and glycemia were measured daily. Glucose, insulin, and pyruvate tolerance, body composition, several hormones, metabolites, gene expression, as well as enzyme activities were determined. Although no effect of oxytocin on the main parameters was observed in lean mice, the treatment dose-dependently reduced food intake and body weight gain in ob/ob animals. Carbetocin behaved similarly to oxytocin, whereas [Thr4,Gly7]-oxytocin (TGOT) and a low oxytocin dose decreased body weight gain without affecting food intake. The body weight gain-reducing effect was limited to the fat mass only, with decreased lipid uptake, lipogenesis, and inflammation, combined with increased futile cycling in abdominal adipose tissue. Surprisingly, oxytocin treatment of ob/ob mice was accompanied by a worsening of basal glycemia and glucose tolerance, likely due to increased corticosterone levels and stimulation of hepatic gluconeogenesis. These results impose careful selection of the conditions in which oxytocin treatment should be beneficial for obesity and its comorbidities, and their relevance for human pathology needs to be determined.
authors.affiliation: Laboratory of Metabolism (J.A., A.-L.P., A.C., C.V.-D., J.L., F.R.-J.), Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland; and Department of Medicine/Physiology (D.A., A.D.), University of Fribourg, Fribourg 1700, Switzerland.
authors.forename: Jordi
authors.initials: J
authors.lastname: Altirriba
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Poher
authors.forename: Aurélie
authors.initials: A
authors.lastname: Caillon
authors.forename: Denis
authors.initials: D
authors.lastname: Arsenijevic
authors.forename: Christelle
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lyautey
authors.forename: Abdul
authors.initials: A
authors.lastname: Dulloo
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D010121:Oxytocin / Q000008:administration & dosage / Q000627:therapeutic use*; D013851:Thinness / Q000378:metabolism / Q000473:pathology
chemical_list: D010121:Oxytocin; D005947:Glucose