Suppression of fat deposition for the life time with gene therapy

被引:27
作者
Boghossian, S
Lecklin, A
Torto, R
Kalra, PS
Kalra, SP
机构
[1] Univ Florida, Coll Med, Dept Neurosci, McKnight Brain Inst, Gainesville, FL 32610 USA
[2] Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32610 USA
[3] Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland
关键词
leptin; gene therapy; obesity; lifetime;
D O I
10.1016/j.peptides.2005.03.039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Unexpended energy is stored as fat in the body and increased rate of fat accretion culminates in obesity. Obesity increases the risks of many diseases several folds and shortens life span. A progressive deficit in the central feedback effects of leptin, a peptide produced by fat cells and hypothalamus, results in increased weight gain and obesity. This article summarizes our experimental findings to show that a stable increase in leptin availability in the hypothalamus alone with the aid of leptin gene therapy suppresses fat accretion and metabolic hormones for nearly the lifetime of laboratory rodents. Consequently, central leptin gene therapy is a novel modality that offers a viable therapeutic option to reduce fat depots and attendant metabolic sequelae implicated in obesity-related illnesses. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:1512 / 1519
页数:8
相关论文
共 65 条
[51]  
RHINEHART EK, 2004, PHYSL FUNCTIONAL GEN, P103
[52]  
Snyder RO, 1999, J GENE MED, V1, P166
[53]   Obesity and the regulation of energy balance [J].
Spiegelman, BM ;
Flier, JS .
CELL, 2001, 104 (04) :531-543
[54]  
TORTO R, 2004, 34 ANN SOC NEUR M SA, pM32
[55]   Ghrelin acts on leptin-responsive neurones in the rat arcuate nucleus [J].
Traebert, M ;
Riediger, T ;
Whitebread, S ;
Scharrer, E ;
Schmid, HA .
JOURNAL OF NEUROENDOCRINOLOGY, 2002, 14 (07) :580-586
[56]   Ghrelin induces adiposity in rodents [J].
Tschöp, M ;
Smiley, DL ;
Heiman, ML .
NATURE, 2000, 407 (6806) :908-913
[57]   Leptin modulates orexigenic effects of ghrelin and attenuates adiponectin and insulin levels and selectively the dark-phase feeding as revealed by central leptin gene therapy [J].
Ueno, N ;
Dube, MG ;
Inui, A ;
Kalra, PS ;
Kalra, SP .
ENDOCRINOLOGY, 2004, 145 (09) :4176-4184
[58]  
UENO N, 2002, P 32 ANN SOC NEUR SC, P781
[59]   Diet-induced obese mice develop peripheral, but not central, resistance to leptin [J].
VanHeek, M ;
Compton, DS ;
France, CF ;
Tedesco, RP ;
Fawzi, AB ;
Graziano, MP ;
Sybertz, EJ ;
Strader, CD ;
Davis, HR .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (03) :385-390
[60]   Comparing the hypothalamic and extrahypothalamic actions of endogenous hyperleptinemia [J].
Wang, ZW ;
Zhou, YT ;
Kakuma, T ;
Lee, Y ;
Higa, M ;
Kalra, SP ;
Dube, MG ;
Kalra, PS ;
Unger, RH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (18) :10373-10378