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

在实验室啮齿动物中，从幼年开始适度限制热量摄入而不营养不良，可以显著减缓衰老过程并延长这些动物的寿命。我们研究了瘦素血浆浓度降低在神经内分泌改变中的作用，可能与热量限制（CR）的抗衰老作用有关。首先，给CR大鼠皮下植入渗透泵，给予瘦素2周。用逆转录聚合酶链反应方法测定下丘脑弓状核神经肽特异性mRNA水平。在本研究中，CR大鼠的血浆瘦素浓度意外波动，这是因为外周给予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，瘦素被给予脑室渗透泵，以规避血浆瘦素浓度的波动。当瘦素给于自由进食（AL）的对照大鼠时，摄食量、脂肪组织和体重减少。在CR大鼠中，瘦素给药改变了每日的食物摄入模式，但没有减少食物摄入，减少了脂肪组织的数量，但没有显着降低体重。这些结果表明，CR大鼠对外源性瘦素的反应不同于AL大鼠。目前，瘦素对弓状核中神经肽Y和阿黑皮素原的mRNA水平、基因表达谱以及葡萄糖和脂质代谢的生物标志物的影响正在研究中。

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.