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/endo.140.2.6491
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发表时间：
1999-02
期刊：
影响因子：
4.8
通讯作者：
T. Mizuno;C. Mobbs
中科院分区：
文献类型：
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作者：
T. Mizuno;C. Mobbs
Agouti-related protein（AGRP）是Agouti-related protein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在下丘脑弓状核中产生，并在瘦素缺乏的ob/ob和瘦素抵抗的db/db小鼠中升高。这些数据表明，AGRP mRNA可能与NPY mRNA平行地受到瘦素和营养状况的影响。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。通过北方印迹分析评估，与野生型对照组相比，ob/ob小鼠AGRP mRNA升高约5倍，瘦素治疗显著抑制AGRP mRNA。在野生型小鼠中，AGRP mRNA增加至少13倍，由2天的快速，评估通过北方印迹分析和原位杂交。在自由进食db/db小鼠中，AGRP mRNA比自由进食野生型对照组升高约8倍，并且在db/db小鼠中通过禁食进一步增加。这些数据表明AGRP mRNA和NPY mRNA对瘦素和禁食的反应相似。
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 lib 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.