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

Zachary S. Roberts, Tami Wolden-Hanson, Miles E. Matsen, Vitaly Ryu, Cheryl H. Vaughan, James L. Graham, Peter J Havel, Daniel W. Chukri, Michael W. Schwartz, Gregory J. Morton, James E. Blevins

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)R357-R371
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume313
Issue number4
DOIs
StatePublished - Oct 1 2017

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Reducing Diet
Rhombencephalon
Oxytocin
Brown Adipose Tissue
Thermogenesis
Energy Intake
Diet
Energy Metabolism
Weight Loss
Oxytocin Receptors
Obese Mice
Solitary Nucleus
Paraventricular Hypothalamic Nucleus
Sympathetic Nervous System
Prosencephalon
Primates
Rodentia
Spinal Cord
Eating
Fats

Keywords

  • Brown adipose tissue
  • Obesity
  • Oxytocin
  • Thermogenesis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Chronic hindbrain administration of oxytocin is sufficient to elicit weight loss in diet-induced obese rats. / Roberts, Zachary S.; Wolden-Hanson, Tami; Matsen, Miles E.; Ryu, Vitaly; Vaughan, Cheryl H.; Graham, James L.; Havel, Peter J; Chukri, Daniel W.; Schwartz, Michael W.; Morton, Gregory J.; Blevins, James E.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 313, No. 4, 01.10.2017, p. R357-R371.

Research output: Contribution to journalArticle

Roberts, ZS, Wolden-Hanson, T, Matsen, ME, Ryu, V, Vaughan, CH, Graham, JL, Havel, PJ, Chukri, DW, Schwartz, MW, Morton, GJ & Blevins, JE 2017, 'Chronic hindbrain administration of oxytocin is sufficient to elicit weight loss in diet-induced obese rats', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 313, no. 4, pp. R357-R371. https://doi.org/10.1152/ajpregu.00169.2017
Roberts, Zachary S. ; Wolden-Hanson, Tami ; Matsen, Miles E. ; Ryu, Vitaly ; Vaughan, Cheryl H. ; Graham, James L. ; Havel, Peter J ; Chukri, Daniel W. ; Schwartz, Michael W. ; Morton, Gregory J. ; Blevins, James E. / Chronic hindbrain administration of oxytocin is sufficient to elicit weight loss in diet-induced obese rats. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2017 ; Vol. 313, No. 4. pp. R357-R371.
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AU - Wolden-Hanson, Tami

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AU - Ryu, Vitaly

AU - Vaughan, Cheryl H.

AU - Graham, James L.

AU - Havel, Peter J

AU - Chukri, Daniel W.

AU - Schwartz, Michael W.

AU - Morton, Gregory J.

AU - Blevins, James E.

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N2 - 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.

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KW - Obesity

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