| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CALL FOR PAPERS
Peptides that Regulate Food Intake
1Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, 32608-1197, and Departments of 2Pharmacology and Therapeutics and 3Molecular Genetics, University of Florida College of Medicine, Gainesville, Florida 32610
Submitted 11 April 2003 ; accepted in final form 11 August 2003
ABSTRACT
The objective of this study was to determine if central overexpression of leptin could overcome the leptin resistance caused by 100 days of high-fat feeding. Three-month old-F344XBN male rats were fed either control low fat chow (Chow), which provides 15% of energy as fat, or a high-fat/high-sucrose diet (HF), which provides 59% of energy as fat. Over several weeks, the HF-fed animals spontaneously split into two groups of animals: those that became obese on the HF diet (DIO) and those that did not gain extra weight on the HF diet [diet resistant (DR)]. After 100 days of HF feeding, animals were given a single intracerebroventricular injection containing 5.75E10 particles of rAAV encoding leptin (rAAV-leptin) or control virus (rAAV-con). Chow animals responded robustly to rAAV-leptin, including significant anorexia, weight loss, and lipopenia. In contrast, DIO were completely unresponsive to rAAV-leptin. DR rats responded to rAAV-leptin, but in a more variable fashion than Chow. Unlike what was observed in Chow, the anorectic response to rAAV-leptin rapidly attenuated and was no longer significant by day 14 postvector delivery. Both DIO and DR animals were found to have reduced long-form leptin receptor expression and enhanced basal P-STAT-3 in the hypothalamus with respect to Chow. rAAV-leptin caused an increase in STAT3 phosphorylation and proopiomelanocortin expression in the hypothalamus and an increase in uncoupling protein-1 in brown adipose tissue in both Chow and DR animals, but failed to do so in DIO. This suggests that central overexpression of leptin is not a viable strategy to reverse diet-induced obesity.
STAT3; neuropeptide Y; proopiomelanocortin; uncoupling protein-1; adeno-associated virus
This article has been cited by other articles:
|
|
 |
|
  M. Matheny, Y. Zhang, A. Shapiro, N. Tumer, and P. J. Scarpace Central overexpression of leptin antagonist reduces wheel running and underscores importance of endogenous leptin receptor activity in energy homeostasis Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1254 - R1261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Shapiro, W. Mu, C. Roncal, K.-Y. Cheng, R. J. Johnson, and P. J. Scarpace Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1370 - R1375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Judge, J. Zhang, N. Tumer, C. Carter, M. J. Daniels, and P. J. Scarpace Prolonged hyperphagia with high-fat feeding contributes to exacerbated weight gain in rats with adult-onset obesity Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2008; 295(3): R773 - R780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Geliebter, C. N. Ochner, and R. Aviram-Friedman Appetite-Related Gut Peptides in Obesity and Binge Eating Disorder American Journal of Lifestyle Medicine, July 1, 2008; 2(4): 305 - 314. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Shapiro, M. Matheny, Y. Zhang, N. Tumer, K.-Y. Cheng, E. Rogrigues, S. Zolotukhin, and P. J. Scarpace Synergy Between Leptin Therapy and a Seemingly Negligible Amount of Voluntary Wheel Running Prevents Progression of Dietary Obesity in Leptin-Resistant Rats Diabetes, March 1, 2008; 57(3): 614 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Augustine, S. R. Ladyman, and D. R. Grattan From feeding one to feeding many: hormone-induced changes in bodyweight homeostasis during pregnancy J. Physiol., January 15, 2008; 586(2): 387 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, M. K. Matheny, N. Tumer, M. K. Mitchell, and P. J. Scarpace Leptin antagonist reveals that the normalization of caloric intake and the thermic effect of food after high-fat feeding are leptin dependent Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R868 - R874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pocai, K. Morgan, C. Buettner, R. Gutierrez-Juarez, S. Obici, and L. Rossetti Central Leptin Acutely Reverses Diet-Induced Hepatic Insulin Resistance Diabetes, November 1, 2005; 54(11): 3182 - 3189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Cupples Physiological regulation of food intake Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1438 - R1443. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
