Chronic CNS Oxytocin Signaling Preferentially Induces Fat Loss in High-Fat Diet-Fed Rats by Enhancing Satiety Responses and Increasing Lipid Utilization

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adiposity / physiology*
  • Animals
  • Appetite / physiology
  • Brain / physiology*
  • Craving / physiology
  • Diet, High-Fat / methods*
  • Dietary Fats / metabolism
  • Infusions, Intraventricular
  • Lipid Metabolism / physiology*
  • Male
  • Obesity / physiopathology
  • Obesity / prevention & control
  • Oxytocin / administration & dosage
  • Oxytocin / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Satiety Response / physiology*
  • Signal Transduction / physiology
  • Weight Loss / physiology

Substances

  • Dietary Fats
  • Oxytocin