title: Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization.
abstract: Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration of oxytocin to rats can both prevent and treat diet-induced obesity.
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: Veterans Affairs Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, Washington;
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Thompson
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;
authors.forename: Vishwanath T
authors.initials: VT
authors.lastname: Anekonda
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: Jacqueline M
authors.initials: JM
authors.lastname: Ho
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: Veterans Affairs Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, Washington;
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Roberts
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;
authors.forename: Bang H
authors.initials: BH
authors.lastname: Hwang
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, Washington;
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ogimoto
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;
authors.forename: Tami
authors.initials: T
authors.lastname: Wolden-Hanson
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, Washington;
authors.forename: Jarrell
authors.initials: J
authors.lastname: Nelson
authors.affiliation: Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, Washington;
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Kaiyala
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
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: Gregory J
authors.initials: GJ
authors.lastname: Morton
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
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000818:Animals; D001066:Appetite / Q000502:physiology; D001921:Brain / Q000502:physiology*; D066249:Craving / Q000502:physiology; D059305:Diet, High-Fat / Q000379:methods*; D004041:Dietary Fats / Q000378:metabolism; D057967:Infusions, Intraventricular; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000503:physiopathology / Q000517:prevention & control; D010121:Oxytocin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015431:Weight Loss / Q000502:physiology
chemical_list: D004041:Dietary Fats; D010121:Oxytocin
keywords: energy expenditure; food intake; obesity; oxytocin