Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats
Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats
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DOI：
10.1007/s00125-002-0851-4
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发表时间：
2002-07-01
期刊：
影响因子：
8.2
通讯作者：
Ros, M
中科院分区：
文献类型：
--
作者：
Fernández-Galaz, C;Fernández-Agulló, T;Ros, M
目标/假设。哺乳动物的衰老与胰岛素和瘦素抵抗有关。这些变化可能是由与衰老相关的肥胖增加引起的，也可能是单独由衰老引起的，也可能是两者兼而有之。我们研究了Wistar大鼠的瘦素抵抗是否发生在中枢水平，我们的目的是区分衰老的影响和与衰老相关的肥胖增加的影响。在幼年Wistar大鼠、老年Wistar大鼠和老年Wistar大鼠的脑室内恒速注入瘦素，用渗透压泵禁食3个月。分析其对体重、每日摄食量、Lee指数、肥胖和血清瘦素水平的影响。此外，还观察了限食对下丘脑Leptin受体长型表达的影响。瘦素减少了年轻和老年Wistar大鼠的每日摄食量和体重。每天给药10杯时，青年和老年大鼠的上述反应相似，但每天给药0.2杯时，只有青年大鼠的上述指标有所下降。限制饮食可使老年大鼠的肥胖度和血清瘦素水平降至接近青年大鼠水平，恢复对静脉注射的反应性。每天服用0.2杯瘦素，可增加下丘脑中瘦素受体的表达。我们的数据显示，老年Wistar大鼠在中枢水平对瘦素的反应降低。食物限制可以恢复下丘脑的瘦素反应，增加下丘脑的瘦素受体，这表明肥胖在与衰老相关的瘦素抵抗的发展中起着关键作用。
Aims/hypothesis. Ageing is associated with insulin and leptin resistance in mammals. These alterations might be caused by the increased adiposity associated with ageing, by ageing alone or both. We studied whether leptin resistance occurs at the central level in the Wistar rat and we aimed to discriminate between the effects of ageing from those of the increased adiposity associated with ageing.Methods. Leptin was infused intracerebroventricularly at a constant rate in young adult, old and old Wistar rats fasted for 3 months, using osmotic pumps. The effects on body weight, daily food intake, Lee index, adiposity and serum leptin values were analysed. The effect of food restriction on the expression of the long form of leptin receptor in the hypothalamus was also studied.Results. Leptin decreased daily food intake and body weight in young and old Wistar rats. With a dose of 10 mug/day similar responses were obtained in young and old rats but with a dose of 0.2 mug/day, only young rats showed decreases in these parameters. Food-restriction in old rats lowered adiposity and serum leptin to values close to those of young rats, recovered responsiveness to i.c.v. administration of leptin at the dose of 0.2 mug/day and increased leptin receptor expression in the hypothalamus.Conclusion/interpretation. Our data show that old Wistar rats have a decreased response to leptin at the central level. Food-restriction recovers leptin responsiveness and increases leptin receptor in the hypothalamus suggesting that adiposity plays a key role in the development of leptin resistance associated with ageing.