title: Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys.
abstract: Despite compelling evidence that oxytocin (OT) is effective in reducing body weight (BW) in diet-induced obese (DIO) rodents, studies of the effects of OT in humans and rhesus monkeys have primarily focused on noningestive behaviors. The goal of this study was to translate findings in DIO rodents to a preclinical translational model of DIO. We tested the hypothesis that increased OT signaling would reduce BW in DIO rhesus monkeys by inhibiting food intake and increasing energy expenditure (EE). Male DIO rhesus monkeys from the California National Primate Research Center were adapted to a 12-h fast and maintained on chow and a daily 15% fructose-sweetened beverage. Monkeys received 2× daily subcutaneous vehicle injections over 1 wk. We subsequently identified doses of OT (0.2 and 0.4 mg/kg) that reduced food intake and BW in the absence of nausea or diarrhea. Chronic administration of OT for 4 wk (0.2 mg/kg for 2 wk; 0.4 mg/kg for 2 wk) reduced BW relative to vehicle by 3.3 ± 0.4% (≈0.6 kg; P < 0.05). Moreover, the low dose of OT suppressed 12-h chow intake by 26 ± 7% (P < 0.05). The higher dose of OT reduced 12-h chow intake by 27 ± 5% (P < 0.05) and 8-h fructose-sweetened beverage intake by 18 ± 8% (P < 0.05). OT increased EE during the dark cycle by 14 ± 3% (P < 0.05) and was associated with elevations of free fatty acids and glycerol and reductions in triglycerides suggesting increased lipolysis. Together, these data suggest that OT reduces BW in DIO rhesus monkeys through decreased food intake as well as increased EE and lipolysis.
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, Washington; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, Washington; jeblevin@u.washington.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Blevins
authors.affiliation: Department of Nutrition and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California; and.
authors.forename: James L
authors.initials: JL
authors.lastname: Graham
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, Washington;
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Morton
authors.affiliation: Department of Psychology, University of California, Davis, California.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Bales
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, Washington;
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, Washington; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, Washington;
authors.forename: Denis G
authors.initials: DG
authors.lastname: Baskin
authors.affiliation: Department of Nutrition and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California; and.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Havel
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage*; D001067:Appetite Depressants / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D004040:Dietary Carbohydrates; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D005632:Fructose; D007279:Injections, Subcutaneous; D008055:Lipids / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D010121:Oxytocin / Q000008:administration & dosage*; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D019440:Anti-Obesity Agents; D001067:Appetite Depressants; D015415:Biomarkers; D004040:Dietary Carbohydrates; D008055:Lipids; D005632:Fructose; D010121:Oxytocin
keywords: energy expenditure; food intake; obesity; oxytocin