Mechanisms underlying the anti-aging effect of caloric restriction: A role for leptin in regulation of neuroendocrine system

热量限制抗衰老作用的机制：瘦素在神经内分泌系统调节中的作用

基本信息

批准号：
12680779
负责人：
SHIMOKAWA Isao
金额：
$ 2.37万
依托单位：
NAGASAKI UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680779/
关键词：
Caloric restriction Aging Leptin Neuroendocrine

项目摘要

Moderate restriction of caloric intake without malnutrition starting at a young age in laboratory rodents significantly slows aging processes and prolongs the lifespan of these animals. We investigated a role for reduced plasma concentrations of leptin in neuroendocrine alterations possibly relevant to the anti-aging effect of caloric restriction (CR). First, leptin was administered into CR rats with subcutaneouslyimplanted osmotic pumps for 2 weeks. Specific mRNA levels of neuropeptides in the hypothalamic arcuate nuclei were measured by reverse transcription polymerase chain reaction methods. In this study, the plasma concentration of leptin in CR rats was fluctuated unexpectedly, because the peripherallyadministered, exogenous leptin could affect the secretion of endogenous leptin from fat tissues. In 2001, therefore, leptin was given intraventricularly with osmotic pumps to circumvent the fluctuation of plasma leptin concentrations. When leptin was administered into control rats fed ad libitum (AL), the amounts of food intake, fat tissues and body weight were decreased. In CR rats, the leptin administration altered the daily pattern of food intake without reducing the food intake, decreased the amount of fat tissues, but not significantly reduced the body weight. These findings suggest that CR rats responded to exogenous leptin differently from AL rats. At present, the effect of leptin on mRNA levels of neuropeptide Y and proopiomelanocortin in the arcuate nuclei, gene expression profiles, and biomarkers of glucose and lipid metabolism are being investigated.

在实验室啮齿动物的年龄段开始，无营养不良的热量摄入量的适度限制会显着减慢衰老的过程，并延长这些动物的寿命。我们研究了降低血浆瘦素在神经内分泌改变中的作用，可能与热量限制的抗衰老作用有关（CR）。首先，将瘦素用皮下渗透渗透泵施用到CR大鼠中2周。通过逆转录聚合酶链反应方法测量下丘脑弓形核中神经肽的特定mRNA水平。在这项研究中，CR大鼠中瘦素的血浆浓度意外波动，因为外围助剂，外源瘦素可能会影响内源性瘦素从脂肪组织中的分泌。因此，在2001年，用渗透泵静脉注射瘦素，以规避血浆瘦素浓度的波动。当将瘦素施用到饲喂额外的对照大鼠中时，食物摄入量，脂肪组织和体重的量减少。在CR大鼠中，瘦素给药改变了食物摄入的日常摄入量，而不减少食物摄入量，减少了脂肪组织的量，但不会显着降低体重。这些发现表明，CR大鼠对外源瘦素的反应与AL大鼠不同。目前，正在研究瘦素对神经肽y和proopiomelanocortin在弧形核，基因表达谱以及葡萄糖和脂质代谢的生物标志物中的影响。