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Am J Physiol Regul Integr Comp Physiol. 2017 Oct 1;313(4):R357-R371. doi: 10.1152/ajpregu.00169.2017. Epub 2017 Jul 26.

Chronic hindbrain administration of oxytocin is sufficient to elicit weight loss in diet-induced obese rats.

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.
2
University of Washington Diabetes Institute, University of Washington School of Medicine, Seattle, Washington.
3
Department of Biology, Georgia State University, Atlanta, Georgia; and.
4
Center for Obesity Reversal, Georgia State University, Atlanta, Georgia.
5
Departments of Nutrition and Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California.
6
Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
7
Veterans Affairs Puget Sound Health Care System, Office of Research and Development, Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, Washington; jeblevin@u.washington.edu.

Abstract

Oxytocin (OT) administration elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates, and humans by reducing energy intake and increasing energy expenditure. Although the neurocircuitry underlying these effects remains uncertain, OT neurons in the paraventricular nucleus are positioned to control both energy intake and sympathetic nervous system outflow to interscapular brown adipose tissue (BAT) through projections to the hindbrain nucleus of the solitary tract and spinal cord. The current work was undertaken to examine whether central OT increases BAT thermogenesis, whether this effect involves hindbrain OT receptors (OTRs), and whether such effects are associated with sustained weight loss following chronic administration. To assess OT-elicited changes in BAT thermogenesis, we measured the effects of intracerebroventricular administration of OT on interscapular BAT temperature in rats and mice. Because fourth ventricular (4V) infusion targets hindbrain OTRs, whereas third ventricular (3V) administration targets both forebrain and hindbrain OTRs, we compared responses to OT following chronic 3V infusion in DIO rats and mice and chronic 4V infusion in DIO rats. We report that chronic 4V infusion of OT into two distinct rat models recapitulates the effects of 3V OT to ameliorate DIO by reducing fat mass. While reduced food intake contributes to this effect, our finding that 4V OT also increases BAT thermogenesis suggests that increased energy expenditure may contribute as well. Collectively, these findings support the hypothesis that, in DIO rats, OT action in the hindbrain evokes sustained weight loss by reducing energy intake and increasing BAT thermogenesis.

KEYWORDS:

brown adipose tissue; obesity; oxytocin; thermogenesis

PMID:
28747407
DOI:
10.1152/ajpregu.00169.2017
[Indexed for MEDLINE]
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