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Am J Physiol Regul Integr Comp Physiol. 2016 Apr 1;310(7):R640-58. doi: 10.1152/ajpregu.00220.2015. Epub 2016 Jan 20.

Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization.

Author information

1
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.
2
Veterans Affairs Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, Washington;
3
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;
4
Department of Nutrition and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California; and.
5
Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, Washington;
6
Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, Washington;
7
Department of Psychology, University of California, Davis, California.
8
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;

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.

KEYWORDS:

energy expenditure; food intake; obesity; oxytocin

PMID:
26791828
PMCID:
PMC4867381
DOI:
10.1152/ajpregu.00220.2015
[Indexed for MEDLINE]
Free PMC Article

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