| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 16, 2006
Accepted on September 27, 2006
Departments of Neurology and Neurosciences, New Jersey Medical School, Newark, New Jersey 07103 and Neurology Service, VA Medical Center, East Orange, NJ 07018
* To whom correspondence should be addressed. E-mail: levin{at}umdnj.edu.
Rats with a genetic predisposition to develop diet-induced obesity (DIO) have a pre-existing reduction in central leptin and insulin sensitivity. High fat diets also reduce sensitivity to leptin, insulin and melanocortin agonists. We postulated that such reduced sensitivities would be associated with decreased binding to the hypothalamic leptin, insulin and melanocortin receptors in selectively bred DIO rats and in rats fed a high-energy (HE; 31% fat) diet for 7 wk. On HE diet, DIO rats gained 15% more weight, had 121% heavier fat pads and 70% higher leptin levels than low fat chow-fed DIO rats. Diet-resistant (DR) rats gained no more weight on HE diet but had 48% heavier fat pads and 70% higher leptin levels than chow-fed DR rats. Compared with DR rats, DIO 125I-leptin binding was 41%, 36% and 40% lower in the hypothalamic dorsomedial, arcuate (ARC), and dorsomedial portion of the ventromedial nuclei, respectively, and ARC 125I-insulin binding was 31% lower independent of diet. In contrast, hypothalamic melanocortin binding did not differ between DIO and DR rats. However, HE diet intake lowered lateral hypothalamic melanocortin-3 and melanocortin-4 receptor (MC4R) and hippocampal insulin binding of both DIO and DR rats and hypothalamic paraventricular nucleus MC4R binding only in DR rats. Neither genotype nor diet affected substantia nigra or ventral tegmental area binding. These results corroborate our previous findings demonstrating a pre-existing decrease in DIO hypothalamic leptin and insulin signaling and demonstrate that HE diet intake reduces hypothalamic melanocortin and hippocampal insulin binding.
This article has been cited by other articles:
 |
|
 |
|
  C. M. Patterson, A. A. Dunn-Meynell, and B. E. Levin Three weeks of early-onset exercise prolongs obesity resistance in DIO rats after exercise cessation Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R290 - R301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Levin Why some of us get fat and what we can do about it J. Physiol., September 1, 2007; 583(2): 425 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Cottone, V. Sabino, T. R. Nagy, D. V. Coscina, and E. P. Zorrilla Feeding microstructure in diet-induced obesity susceptible versus resistant rats: central effects of urocortin 2 J. Physiol., September 1, 2007; 583(2): 487 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Buren, S.-A. Bergstrom, E. Loh, I. Soderstrom, T. Olsson, and C. Mattsson Hippocampal 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Messenger Ribonucleic Acid Expression Has a Diurnal Variability that Is Lost in the Obese Zucker Rat Endocrinology, June 1, 2007; 148(6): 2716 - 2722. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
