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