Acute hypothalamic administration of L-arginine increases feed intake in rats

Objective: This study investigated the chronic (oral) and acute (hypothalamic infusion) effects of L-arginine supplementation on feed intake, body composition, and behavioral changes in rats. Methods: Twenty rats were divided into two groups treated orally for 60 days; one group received L-arginine (1 g/kg body weight) and one group received saline (1 mL/NaCl 0.9%). Daily consumption of water and food were evaluated, and weight monitored. After the oral treatment, the rats underwent stereotactic biopsy and a group was injected with 2 µL of L-arginine (0.5 mM) and another received an injection of saline (0.9% NaCl), in the hypothalamic route, through micro infusion. Immediately after micro infusion, the animal behavior was evaluated through tests in the open field. Food and water consumption were evaluated at 12 and 24 hours after the micro infusion. Daily water consumption and weight gain evolution were evaluated. At the end of treatments, rats were euthanized and blood was collected for glucose, glycerol, and cholesterol evaluation, and histological analysis of vital organs. Results: Oral supplementation with L-arginine increased water intake (11%, p<0.05) and promoted weight gain (3%, p<0.05). However, hypothalamic infusion promoted a significant increase in chow intake (30%, p<0.05) after 24 hours of L-arginine administration. Conclusion: Chronic oral treatment with L-arginine was not effective on appetite modulation; however, an effect was observed when L-arginine was administered directly into the hypothalamus, suggesting a central regulation on appetite through nNOS sensitization. Chronic use of L-arginine did not cause substantial changes in anthropometric, biochemical, behavioral, or histological variables.

研究目的：本研究探讨了补充L-精氨酸(L-arginine)经慢性口服与急性下丘脑输注两种给药方式，对大鼠的摄食行为、身体组成及行为变化的影响。
研究方法：将20只大鼠分为两组，开展为期60天的口服给药干预；其中一组给予L-精氨酸(1 g/kg体重)，另一组给予生理盐水(1 mL/0.9% NaCl)。每日评估大鼠的饮水与摄食量，并监测体重变化。口服给药结束后，对大鼠实施立体定向活检，随后通过微输注方式经下丘脑通路分别注射2 µL L-精氨酸(0.5 mM)与0.9%生理盐水。微输注结束后即刻，通过旷场实验评估动物行为。分别于微输注后12小时与24小时测定摄食量与饮水量。同时持续监测每日饮水量与体重增长变化。干预结束后，对大鼠实施安乐死并采集血液样本，用于检测血糖、甘油与胆固醇水平，并对重要脏器进行组织学分析。
研究结果：口服补充L-精氨酸可提升饮水量11%(p<0.05)，并促进体重增长3%(p<0.05)。然而，经下丘脑输注L-精氨酸后24小时，可显著提升大鼠的日粮摄食量30%(p<0.05)。
研究结论：慢性口服L-精氨酸对食欲调控无显著效果，但当L-精氨酸直接给药至下丘脑时则可观察到调控效应，提示其通过神经元型一氧化氮合酶(neuronal nitric oxide synthase, nNOS)敏化实现中枢食欲调控。长期使用L-精氨酸未对人体测量学、生化指标、行为学或组织学变量造成显著改变。