Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B
Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B
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DOI：
10.1016/s1534-5807(02)00149-1
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发表时间：
2002-04-01
影响因子：
11.8
通讯作者：
Tremblay, ML
中科院分区：
文献类型：
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作者：
Cheng, A;Uetani, N;Tremblay, ML
常见的肥胖症的主要特征是抵抗激素瘦素的作用。蛋白酪氨酸磷酸酶1B（PTP 1B）缺陷的小鼠对糖尿病和饮食诱导的肥胖具有抵抗力，这促使我们进一步确定PTP 1B和瘦素在调节肥胖中的关系。缺乏PTP 1B的瘦素缺陷（Lep（ob/ob））小鼠表现出体重增加减弱、脂肪组织减少和静息代谢率增加。此外，PTP 1B缺陷小鼠对瘦素介导的体重减轻和摄食抑制的反应增强。这些小鼠的下丘脑也显示出瘦素诱导的Stat 3磷酸化显著增加。最后，底物捕获实验表明，瘦素激活的Jak 2，而不是Stat 3或瘦素受体，是PTP 1B的底物。这些结果表明，PTP 1B负调控瘦素信号，并提供了一种机制，它可以调节肥胖。
Common obesity is primarily characterized by resistance to the actions of the hormone leptin. Mice deficient in protein tyrosine phosphatase 1B (PTP1B) are resistant to diabetes and diet-induced obesity, prompting us to further define the relationship between PTP1B and leptin in modulating obesity. Leptin-deficient (Lep(ob/ob)) mice lacking PTP1B exhibit an attenuated weight gain, a decrease in adipose tissue, and an increase in resting metabolic rate. Furthermore, PTP1B-deficient mice show an enhanced response toward leptin-mediated weight loss and suppression of feeding. Hypothalami from these mice also display markedly increased leptin-induced Stat3 phosphorylation. Finally, substrate-trapping experiments demonstrate that leptin-activated Jak2, but not Stat3 or the leptin receptor, is a substrate of PTP1B. These results suggest that PTP1B negatively regulates leptin signaling, and provide one mechanism by which it may regulate obesity.