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

36 Citations (Scopus)

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

Fingerprint

Satiety Response
High Fat Diet
Oxytocin
Central Nervous System
Fats
Lipids
Obesity
Energy Metabolism
Weight Gain
Meals
Sucrose
Weight Loss
Maintenance
Diet

Keywords

  • Energy expenditure
  • Food intake
  • Obesity
  • Oxytocin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 310, No. 7, 01.04.2016, p. R640-R658.

Research output: Contribution to journalArticle

Blevins, JE, Thompson, BW, Anekonda, VT, Ho, JM, Graham, JL, Roberts, ZS, Hwang, BH, Ogimoto, K, Wolden-Hanson, T, Nelson, J, Kaiyala, KJ, Havel, PJ, Bales, KL, Morton, GJ, Schwartz, MW & Baskin, DG 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, vol. 310, no. 7, pp. R640-R658. https://doi.org/10.1152/ajpregu.00220.2015
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. / Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2016 ; Vol. 310, No. 7. pp. R640-R658.
@article{7ab5c920e446409db0a9df2c5863fc4f,
title = "Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization",
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.",
keywords = "Energy expenditure, Food intake, Obesity, Oxytocin",
author = "Blevins, {James E.} and Thompson, {Benjamin W.} and Anekonda, {Vishwanath T.} and Ho, {Jacqueline M.} and Graham, {James L.} and Roberts, {Zachary S.} and Hwang, {Bang H.} and Kayoko Ogimoto and Tami Wolden-Hanson and Jarrell Nelson and Kaiyala, {Karl J.} and Havel, {Peter J} and Bales, {Karen L.} and Morton, {Gregory J.} and Schwartz, {Michael W.} and Baskin, {Denis G.}",
year = "2016",
month = "4",
day = "1",
doi = "10.1152/ajpregu.00220.2015",
language = "English (US)",
volume = "310",
pages = "R640--R658",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "7",

}

TY - JOUR

T1 - Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization

AU - Blevins, James E.

AU - Thompson, Benjamin W.

AU - Anekonda, Vishwanath T.

AU - Ho, Jacqueline M.

AU - Graham, James L.

AU - Roberts, Zachary S.

AU - Hwang, Bang H.

AU - Ogimoto, Kayoko

AU - Wolden-Hanson, Tami

AU - Nelson, Jarrell

AU - Kaiyala, Karl J.

AU - Havel, Peter J

AU - Bales, Karen L.

AU - Morton, Gregory J.

AU - Schwartz, Michael W.

AU - Baskin, Denis G.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - Energy expenditure

KW - Food intake

KW - Obesity

KW - Oxytocin

UR - http://www.scopus.com/inward/record.url?scp=84964834118&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964834118&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00220.2015

DO - 10.1152/ajpregu.00220.2015

M3 - Article

C2 - 26791828

AN - SCOPUS:84964834118

VL - 310

SP - R640-R658

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 7

ER -