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

在没有营养不良的情况下，从小开始适度限制热量摄入，可以显著减缓实验室啮齿动物的衰老过程，延长这些动物的寿命。我们研究了血浆瘦素浓度降低在神经内分泌改变中的作用，这可能与热量限制（CR）的抗衰老作用有关。首先，通过皮下植入渗透泵给予CR大鼠瘦素2周。用逆转录聚合酶链反应法测定下丘脑弓状核中神经肽的特异性mRNA水平。在本研究中，CR大鼠血浆中瘦素浓度出现了意外波动，这是因为外周给药，外源性瘦素会影响脂肪组织内源性瘦素的分泌。因此，在2001年，通过渗透泵给药瘦素以避免血浆瘦素浓度的波动。对照组大鼠自由饲喂瘦素后，食量、脂肪组织和体重均有所下降。在CR大鼠中，瘦素在不减少食物摄入量的情况下改变了每日进食模式，减少了脂肪组织的数量，但没有显著减少体重。这些发现表明CR大鼠对外源性瘦素的反应与AL大鼠不同。目前，研究人员正在研究瘦素对弓形核中神经肽Y和促黑素原的mRNA水平、基因表达谱和糖脂代谢生物标志物的影响。

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.