Role of brain serotonin systems and ghrelin in the regulation of feeding behavior

脑血清素（5-羟色胺；5-HT）系统有助于调节饮食行为和能量稳态。5-HT2C受体和5-HT1B受体可介导5-HT药物的厌食作用，如刺激5-HT释放并抑制5-HT再摄取的d-芬氟拉明和5-HT2C受体激动剂间氯苯哌嗪（mCPP）。在这里，我们报告了与进食状态相比，24小时禁食增加了下丘脑5-HT2C受体和5-HT1B受体基因的表达，并增加了血浆活性胃饥饿素水平。用mCPP或芬氟拉明治疗可显著抑制血浆活性胃饥饿素水平的升高。mCPP或芬氟拉明显著增加下丘脑前鸦片黑素皮质激素和可卡因、安非他明调控转录基因的表达，而对下丘脑神经肽Y、agouti相关蛋白和ghrelin基因的表达无显著影响。这些结果表明，在小鼠能量稳态中，大脑5-羟色胺系统和血浆活性胃饥饿素水平之间存在负反馈系统（BBRC 341:703,2006）。血清和糖皮质激素诱导的蛋白激酶（SGK）是一种丝氨酸/苏氨酸特异性蛋白激酶，受血清、糖皮质激素和矿物皮质激素的转录调节。在这里，我们报告了空腹或肥胖伴贪食增加下丘脑SGK-1基因表达。C57BL6J小鼠、KK小鼠和KKA^y小鼠下丘脑SGK-1 mRNA水平与日摄食量和体重成正比。在这些动物中，血浆去酰基胃饥饿素（而非活性胃饥饿素）水平与每日食物摄入量和体重成反比。在能量消耗增加的条件下（如禁食），下丘脑SGK-1基因表达与血浆去酰基胃饥饿素水平呈正相关，而在能量储存增加的条件下，两者呈负相关。这些结果表明下丘脑SGK-1基因是参与小鼠能量稳态的一个新的候选基因（BBRC 344:696,2006）。少

Brain serotonin (5-hydroxytryptamine ; 5-HT) systems contribute to regulate eating behavior and energy homeostasis. 5-HT2C receptors and 5-HT1B receptors have been shown to mediate anorexic effects of 5-HT drugs such as d-fenfluramine, which stimulates 5-HT release and inhibits 5-HT reuptake, and m-chlorophenylpiperazine (mCPP), a 5-HT2C receptor agonist. Here we report that 24-h fasting increased the expression of hypothalamic 5-HT2C receptor and 5-HT1B receptor genes in association with increases in plasma active ghrelin levels compared with fed state in mice. Treatment with mCPP or fenfluramine significantly inhibited the increases in plasma active ghrelin levels. mCPP or fenfluramine significantly increased the expression of hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript genes while having no significant effects on the expression of hypothalamic neuropeptide Y, agouti- related protein and ghrelin genes. These results suggest that there is a nega … More tive feedback system between brain 5-HT systems and plasma active ghrelin levels in energy homeostasis in mice (BBRC 341:703,2006).Serum- and glucocorticoid-induced protein kinase (SGK) is a serine/threonine-specific protein kinase that is transcriptionally regulated by serum, glucorticoids, and mineral corticoids. Here, we report that fasting or obesity with hyperphagia increased hypothalamic SGK-1 gene expression. Hypothalamic SGK-1 mRNA levels were proportional to daily food intake and body weights in C57BL6J mice, KK mice, and KKA^y mice matched for age. Plasma des-acyl ghrelin, but not active ghrelin, levels were inversely proportional to daily food intake and body weights among these animals. Under conditions of increased energy usage such as fasting, hypothalamic SGK-1 gene expression and plasma des-acyl ghrelin levels were positively correlated while during conditions of increased energy storage, they were negatively correlated. These results suggest that hypothalamic SGK-1 gene is a novel candidate gene involving in energy homeostasis in mice (BBRC 344:696,2006). Less