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

James E. Blevins, Benjamin W. Thompson, Vishwanath T. Anekonda, Jacqueline M. Ho, James L. Graham, Zachary S. Roberts, Bang H. Hwang, Kayoko Ogimoto, Tami Wolden-Hanson, Jarrell Nelson, Karl J. Kaiyala, Peter J Havel, Karen L. Bales, Gregory J. Morton, Michael W. Schwartz, Denis G. Baskin

Research output: Contribution to journalArticle

37 Scopus citations

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 weightreducing 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 dietinduced obesity.

Original languageEnglish (US)
Pages (from-to)R640-R658
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume310
Issue number7
DOIs
StatePublished - Apr 1 2016

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Keywords

  • Energy expenditure
  • Food intake
  • Obesity
  • Oxytocin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Blevins, J. E., Thompson, B. W., Anekonda, V. T., Ho, J. M., Graham, J. L., Roberts, Z. S., Hwang, B. H., Ogimoto, K., Wolden-Hanson, T., Nelson, J., Kaiyala, K. J., Havel, P. J., Bales, K. L., Morton, G. J., Schwartz, M. W., & Baskin, D. G. (2016). Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 310(7), R640-R658. https://doi.org/10.1152/ajpregu.00220.2015