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首页> 外文期刊>The European Journal of Neuroscience >Perinatal protein restriction reduces the inhibitory action of serotonin on food intake.
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Perinatal protein restriction reduces the inhibitory action of serotonin on food intake.

机译：围产期蛋白质限制降低了血清素对食物摄入的抑制作用。

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Early malnutrition has been associated with a high risk of developing obesity, diabetes and cardiovascular diseases in adulthood. In animals, poor perinatal nutrition produces hyperphagia and persistent increased levels of serotonin (5-HT) in the brain. Inasmuch as 5-HT is directly related to the negative regulation of food intake, here we have investigated whether the anorexic effects of 5-HT are altered by protein malnutrition. Pregnant Sprague-Dawley rats were fed ad libitum either a control (20% protein) or a low-protein (8% protein) diet throughout pregnancy and lactation. At weaning, pups received a standard diet and at 35 days their feeding behaviour was evaluated after the administration of DL-fenfluramine (DL-FEN), an anorexic compound that blocks the reuptake of 5-HT and stimulates its release. Male offspring born to protein-restricted dams exhibited significantly decreased body weight and hyperphagia compared with controls. DL-FEN dose-dependently reduced the 1 h chow intake at the onset of the dark cycle in both control and undernourished rats. However, the hypophagic effects of DL-FEN were significantly attenuated in animals submitted perinatally to protein restriction. The stimulatory action of DL-FEN on c-fos immunoreactivity within the paraventricular nucleus of the hypothalamus was also decreased in low-protein-fed rats. Further pharmacological analysis with selective 5-HT(1B) and 5-HT(2C) receptor agonist showed that the reduced anorexic effects of 5-HT in malnourished animals were coupled to a desensitization of 5-HT(1B) receptors. These observations indicate that the hyperphagia associated with metabolic programming is at least partially related to a reduced regulatory function of 5-HT on food intake.
机译：早期营养不良与成年后肥胖，糖尿病和心血管疾病的高风险相关。在动物中，围产期营养不良会导致食欲亢进，并使大脑中5-羟色胺（5-HT）水平持续升高。由于5-HT与食物摄入的负调节直接相关，因此我们在此研究了5-HT的厌食症是否因蛋白质营养不良而改变。在怀孕和哺乳期间，随意给怀孕的Sprague-Dawley大鼠喂饲对照（20％蛋白质）或低蛋白（8％蛋白质）饮食。断奶时，幼犬接受标准饮食，并在DL-芬氟拉明（DL-FEN）给药后评估其摄食行为，DL-芬氟拉明是一种厌食性化合物，可阻断5-HT的再摄取并刺激其释放。与对照相比，蛋白质限制性大坝出生的雄性后代的体重和食欲明显降低。在对照组和营养不良的大鼠中，DL-FEN在黑暗周期开始时剂量依赖性地减少了1小时的摄食量。但是，DL-FEN的低吞噬作用在围产期受到蛋白质限制的动物中明显减弱。在低蛋白喂养的大鼠中，DL-FEN对下丘脑室旁核内c-fos免疫反应性的刺激作用也降低了。用选择性5-HT（1B）和5-HT（2C）受体激动剂进行的进一步药理分析表明，营养不良的动物体内5-HT的厌食作用降低与5-HT（1B）受体的脱敏有关。这些观察结果表明，与代谢程序有关的食欲亢进至少部分与5-HT对食物摄入的调节功能降低有关。

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