Role of neuropeptide Y in diet-, chemical- and genetic-induced obesity of mice
Role of neuropeptide Y in diet-, chemical- and genetic-induced obesity of mice
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DOI：
10.1038/sj.ijo.0800615
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发表时间：
1998-06-01
影响因子：
4.9
通讯作者：
Palmiter, RD
中科院分区：
文献类型：
--
作者：
Hollopeter, G;Erickson, JC;Palmiter, RD
目的：本研究的目的是确定小鼠中高脂饮食 (HFD) 引起的肥胖、谷氨酸钠 (MSG) 或硫代金葡萄糖 (GTG) 引起的下丘脑化学损伤、解偶联蛋白 1 启动子驱动的白喉毒素转基因引起的棕色脂肪组织受损 (BAT) 是否需要神经肽 Y (NPY) (UCP-DTA) 或致命的黄色刺豚鼠突变 (A(Y))。 背景：瘦素缺陷 (ob/ob) 小鼠的肥胖综合症可以通过 NPY 的基因去除而部分逆转。在本研究检查的小鼠肥胖模型中，尽管血清瘦素水平升高，但动物仍变得肥胖，这表明它们对瘦素的体重限制作用具有抵抗力。 NPY 在这些瘦素水平升高的肥胖模型中的作用尚不清楚。 实验设计：由于基因遗传破坏而缺乏 NPY 的小鼠和野生型同窝小鼠通过允许它们获得高度适口的 HFD、用 MSG 或 GTG 治疗或通过遗传显性 UCP-DTA 或 A(Y) 等位基因来使它们肥胖。测量食物消耗、体重和可解剖脂肪垫重量，并与从非肥胖同窝小鼠获得的值进行比较。结果：在每个测试的肥胖模型中，NPY缺陷小鼠的食物摄入量、体重和脂肪含量与野生型同窝小鼠相同。结论：NPY对于多种瘦素抵抗小鼠模型所表现出的肥胖的逐渐发展并不是必需的。
OBJECTIVE: The goal of this study was to ascertain whether neuropeptide Y (NPY) is required in mice for the development of obesity induced by a high-fat diet (HFD), chemical lesions of the hypothalamus caused by monosodium glutamate (MSG) or gold thioglucose (GTG), impaired brown adipose tissue (BAT) due to a diphtheria toxin transgene driven by the uncoupling protein 1 promoter (UCP-DTA) or the lethal yellow agouti mutation (A(Y)).BACKGROUND: The obesity syndrome of the leptin-deficient (ob/ob) mouse can be partially reversed by the genetic removal of NPY. In the murine models of obesity examined in this study, the animals become obese despite increased serum leptin levels, indicating that they are resistant to the weight-limiting actions of leptin. The role of NPY in these obesity models with elevated leptin levels is unknown.EXPERIMENTAL DESIGN: Mice lacking NPY due to genetic disruption of the gene and wildtype littermates were made obese by allowing them access to a highly palatable HFD, by treatment with MSG, or GTG, or by inheriting the dominant UCP-DTA or A(Y) alleles. Food consumption, body weight and dissectable fat pad weights were measured and compared to values obtained from non-obese littermates.RESULTS: In each model of obesity tested, NPY-deficient mice achieved the same food intake, body weight and fat content as wildtype littermates.CONCLUSION: NPY is not necessary for the progressive development of obesity exhibited by multiple murine models with leptin resistance.