Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats
Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats
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DOI：
10.1016/s0028-3908(02)00003-5
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发表时间：
2002-03-01
影响因子：
4.7
通讯作者：
Zolotukhin, S
中科院分区：
文献类型：
--
作者：
Scarpace, PJ;Matheny, M;Zolotukhin, S
本研究的目的是确定长期瘦素治疗是否使正常和瘦素抵抗的a-e相关肥胖大鼠的瘦素信号转导和随后的下游趋化和产热反应脱敏。为此，我们进行了静脉注射，将编码大鼠瘦素cDNA的重组腺相关病毒（rAAV-leptin）或对照病毒感染到年轻和老年肥胖大鼠中，并在9或46天后检测摄食量、耗氧量、体重、血清瘦素、STAT 3磷酸化、下丘脑NPY和POMC mRNA。棕色脂肪组织（BAT）中UCP 1的表达和蛋白水平。在年轻大鼠中，rAAV-leptin消耗体脂，并且增重和产热机制都有助于这种效果。而且。瘦素信号转导没有脱敏。并且有持续的生理反应。同样。在老年肥胖大鼠中。然而，瘦素信号转导并没有减弱。在第9天后的某个时间，热刺激和产热反应都完全减弱。这种衰减。瘦素受体的下游，可能有助于这些老年肥胖大鼠的瘦素抵抗和年龄相关的体重增加。终于来了在年轻大鼠中，尽管对rAAV-瘦素的初始反应以抗瘦素反应为主。到46天时，主要的反应是产热而不是增重，这表明能量消耗可能是长期体重维持的重要组成部分。出版社：Elsevier Science Ltd
The purpose of this study was to determine if long-term leptin treatment desensitizes leptin signal transduction and the Subsequent downstream anorexic and thermogenic responses in normal and leptin-resistant a-e-related obese rats. To this end, we administered, i.c.v., recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or control Virus into young and aged-obese rats and after 9 or 46 days, examined food intake, oxygen consumption, body weight, scrum leptin, STAT3 phosphorylation, hypothalamic NPY and POMC mRNAs. and UCP1 expression and protein level in brown adipose tissue (BAT). In young rats, rAAV-leptin depleted body fat and both anorexic and thermogenic mechanisms contributed to this effect. Moreover. leptin signal transduction was not desensitized. and there were persistent physiological responses. Similarly. in the aged-obese rats. there was unabated leptin signal transduction, however. both the anorexic and thermogenic responses completely attenuated sometime after day 9. This attenuation. downstream of the leptin receptor, may be contributing to the leptin-resistance and age-related weight gain in these aged-obese rats. Finally. in young rats, although the initial responses to rAAV-leptin were dominated by anorexic responses. by 46 days, the predominant response was thermogenic rather than anorexic, suggesting that energy expenditure may be an important component of long-term weight maintenance. Published by Elsevier Science Ltd.