Hypothalamic Agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting
Hypothalamic Agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting
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DOI：
10.1210/en.140.2.814
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发表时间：
1999-02-01
期刊：
影响因子：
4.8
通讯作者：
Mobbs, CV
中科院分区：
文献类型：
--
作者：
Mizuno, TM;Mobbs, CV
刺鼠相关蛋白(AGRP)是刺鼠基因产物的同源物，当过度表达时，会促进肥胖。与神经肽Y(NPY)信使RNA(MRNA)一样，AGRP mRNA在下丘脑弓状核产生，在瘦素缺乏的ob/ob和瘦素抵抗的db/db小鼠中升高。这些数据提示，瘦素和营养状态可能与NPY基因同时影响AGRP基因的表达。为了验证这一假设，我们研究了AGRP mRNA是否会像NPY mRNA一样，被瘦素注射抑制，并被禁食刺激。Northern印迹分析表明，与野生型对照相比，肥胖/肥胖小鼠的AgRP mRNA增加了约5倍，并被瘦素治疗显著抑制。在野生型小鼠中，AGRP mRNA在禁食2天后至少增加了13倍，通过Northern印迹分析和原位杂交进行了评估。在随机饲养的db/db小鼠中，AGRP mRNA的表达比随机喂养的野生型对照小鼠高约8倍，在db/db小鼠中禁食后进一步增加。这些数据表明，AGRP和NPY mRNA对瘦素和空腹的反应相似。
Agouti-related protein (AGRP) is a homologue of the agouti gene product and, when overexpressed, promotes obesity. Like neuropeptide Y (NPY) messenger RNA (mRNA), AGRP mRNA is produced in the hypothalamic arcuate nucleus and is elevated in leptin-deficient ob/ob and leptin-resistant db/db mice. These data suggest that AGRP mRNA might be affected by leptin and nutritional status in parallel with NPY mRNA. To test this hypothesis, we examined if AGRP mRNA would be, like NPY mRNA, inhibited by leptin injections and stimulated by fasting. AGRP mRNA was elevated in ob/ob mice about 5-fold compared with wild-type controls and was significantly inhibited by leptin treatment, as assessed by Northern blot analysis. In wild-type mice, AGRP mRNA was increased at least 13-fold by a 2-day fast, as assessed both by Northern blot analysis and in situ hybridization. In ad lib fed db/db mice, AGRP mRNA was elevated about 8-fold compared with ad rib fed wild-type controls, and was further increased by fasting in db/db mice. These data suggest that AGRP mRNA and NPY mRNA respond similarly to leptin and fasting.