Hypothalamic rAAV-mediated GDNF gene delivery ameliorates age-related obesity

被引：22

作者：

Tümer, N

Scarpace, PJ

Dogan, MD

Broxson, CS

Matheny, M

Yurek, DM

Peden, CS

Burger, C

Muzyczka, N

Mandel, RJ

机构：

[1] Dept Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Gainesville, FL 32608 USA

[2] Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA

[3] Univ Kentucky, Coll Med, Dept Surg, Lexington, KY 40506 USA

[4] Univ Florida, Coll Med, Dept Microbiol & Med Genet, Gainesville, FL 32610 USA

[5] Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL 32610 USA

[6] Univ Florida, Coll Med, McKnight Brain Inst, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA

来源：

NEUROBIOLOGY OF AGING | 2006年 / 27卷 / 03期

关键词：

GDNF; gene delivery; hypothalamus; aging; obesity;

D O I：

10.1016/j.neurobiolaging.2005.03.018

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Intraventricular delivery of glial cell fine-derived neurotrophic factor (GDNF) results in weight loss. We hypothesized that this effect of GDNF was likely mediated via its effects on dopaminergic neurons in the hypothalamus. Continuous rAAV-mediated GDNF expression in the hypothalamus of young and senescent rats resulted in weight loss compared to controls. However, GDNF-induced weight loss was unrelated to alterations in hypothalamic dopamine levels. The weight loss was associated with decreased food intake and increased energy expenditure, but these effects were not mediated by changes in hypothalamic NPY or POMC expression. Moreover. uncoupling protein I levels were unchanged in brown adipose tissue (BAT). The reduction in weight and adiposity were as great or greater in the aged rats even though aged rats are generally resistant to weight loss therapies. In summary, central GDNF gene delivery reduces weight and adiposity in young and aged rats through decreased food intake and increased energy expenditure. Our observations in aged rats suggest that GDNF may be especially effective in reducing obesity in aged obese rats. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：459 / 470

页数：12

共 40 条

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