| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Pharmacology, University of Florida, Gainesville, Florida, United States
2 Pharmacology, University of Florida, Gainesville, Florida, United States; Geriatric Research, Education and Clinical Center, University of Florida, VA Medical Center, Gainesville, Florida, United States
* To whom correspondence should be addressed. E-mail: scarpace{at}ufl.edu.
High-fat feeding induces a transient increase in caloric intake and enhances energy expenditure. We hypothesized that leptin is necessary for the homeostatic restoration of the high-fat enhanced caloric intake and may mediate the increase in BAT UCP1 protein. We employed a leptin antagonist to examine the role of leptin in these biological processes. Simultaneous central administration of leptin and increasing doses of the leptin antagonist revealed a dose-dependent inhibition of leptin-induced hypothalamic STAT3 phosphorylation, and a 7-day infusion of the leptin antagonist produced the predicted increase in food intake and weight gain. When delivered with exogenous leptin in a 7-day infusion, the leptin antagonist blocked leptin-mediated anorexic effects as well as the increase in BAT UCP1 protein and STAT3 phosphorylation. Rats were then provided with a high-fat (HF) diet (60% kcal as fat) or chow and simultaneously infused with antagonist (25µg/d, lateral ventricle) for 7 days and compared to vehicle infused chow-fed rats. Daily caloric intake of both HF groups peaked on day 2. HF feeding elevated caloric intake that nearly normalized by day 7, whereas in the presence of the antagonist, caloric intake remained elevated. Moreover, the HF-mediated augmentation in UCP1 in brown adipose tissue was prevented by the antagonist. These results demonstrate that leptin is essential for the homeostatic restoration of caloric intake following high-fat feeding; and this leptin antagonist is able to block central leptin signaling and leptin-mediated UCP1 elevation.
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]
|
|
|
|
|
|
P. J. Scarpace and Y. Zhang Leptin resistance: a prediposing factor for diet-induced obesity Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R493 - R500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. White, A. Whittington, M. J. Barnes, Z. Wang, G. A. Bray, and C. D. Morrison HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E291 - E299. [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]
|
|
|
|
|
|
K. Begriche, P. Letteron, A. Abbey-Toby, N. Vadrot, M.-A. Robin, A. Bado, D. Pessayre, and B. Fromenty Partial leptin deficiency favors diet-induced obesity and related metabolic disorders in mice Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E939 - E951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yang and L. A. Barouch Leptin Signaling and Obesity: Cardiovascular Consequences Circ. Res., September 14, 2007; 101(6): 545 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-Y. Zhang and D.-H. Wang Thermogenesis, food intake and serum leptin in cold-exposed lactating Brandt's voles Lasiopodomys brandtii J. Exp. Biol., February 1, 2007; 210(3): 512 - 521. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
