| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
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.
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