Changes in gene expressions of hypothalamic neuropeptides controlling feeding behaviors in bilateral nephrectomized rats
Changes in gene expressions of hypothalamic neuropeptides controlling feeding behaviors in bilateral nephrectomized rats
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双侧肾切除大鼠下丘脑神经肽控制摄食行为的基因表达变化
DOI：
10.1016/j.neulet.2019.134426
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发表时间：
2019
影响因子：
2.5
通讯作者：
Ueta Yoichi
中科院分区：
文献类型：
--
作者：
Ueno Hiromichi;Miyamoto Tetsu;Sanada Kenya;Nakazono Kazutoshi;Tanaka Kentaro;Nishimura Haruki;Nishimura Kazuaki;Sonoda Satomi;Yoshimura Mitsuhiro;Maruyama Takashi;Serino Ryota;Otsuji Yutaka;Ueta Yoichi
厌食症是最普遍的饮食失调之一，似乎有助于晚期肾功能不全患者的营养不良。在多种生理条件下，下丘脑合成的控制摄食行为的神经肽发生变化，可引起厌食。虽然已经提出了尿毒症厌食症的几种机制，但对尿毒症患者下丘脑控制进食行为的神经肽的变化知之甚少。采用原位杂交组织化学方法，观察了急性肾功能不全模型大鼠双侧肾切除后下丘脑摄食神经肽基因表达的变化。双侧肾切除大鼠的摄食量明显减少。双侧肾切除大鼠的促肾上腺皮质激素释放激素、阿黑皮素原、可卡因和苯丙胺调节的抑制摄食行为的转录物的mRNA水平显著高于假手术大鼠。另一方面，双侧肾切除大鼠的Agouti-related peptide、neuropeptide Y、melanin-concentrating hormone和dorexin的mRNA水平显著低于假手术大鼠。此外，血浆瘦素水平，这有一个减肥的效果，增加后，双侧肾切除术。结果提示，控制摄食行为的下丘脑神经肽可能参与了双侧肾切除大鼠厌食症的发生。本报告是阐明肾功能不全患者厌食症的生理机制的第一步。
Anorexia is one of the most widespread eating disorders that appears to contribute to malnutrition in patients with advanced kidney dysfunction. The changes of neuropeptides controlling feeding behaviors synthesized in the hypothalamus under several physiological condition could induce anorexia. While several mechanisms underlying uremic anorexia have been proposed, the changes of hypothalamic neuropeptides controlling feeding behaviors of uremic patients are poorly understood. The gene expressions of hypothalamic neuropeptides controlling feeding behaviors were evaluated after bilateral nephrectomy, which is a model of acute kidney dysfunction, byin situhybridization histochemistry. Food consumption decreased markedly in bilateral nephrectomized rats. The mRNA levels ofcorticotrophin-releasing hormone,proopiomelanocortin,cocaine- and amphetamine-regulated transcript, which suppress feeding behavior, were significantly higher in bilateral nephrectomized rats than in sham-operated rats. On the other hand, the mRNA levels ofAgouti-related peptide,neuropeptide Y,melanin-concentrating hormone, andorexin, which promote feeding behavior, were significantly lower in bilateral nephrectomized rats than in sham-operated rats. In addition, the plasma level of leptin, which has an anorexic effect, increased after bilateral nephrectomy. The results suggest that hypothalamic neuropeptides controlling feeding behaviors may be involved in the development of anorexia in bilateral nephrectomized rats. This report is the first step to elucidating the physiological mechanisms of anorexia in patients with kidney dysfunction.