PTP1B regulates leptin signal transduction in vivo
PTP1B regulates leptin signal transduction in vivo
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DOI：
10.1016/s1534-5807(02)00148-x
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发表时间：
2002-04-01
影响因子：
11.8
通讯作者：
Neel, BG
中科院分区：
文献类型：
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作者：
Zabolotny, JM;Bence-Hanulec, KK;Neel, BG
缺乏蛋白酪氨酸磷酸酶PTP 1B的小鼠对胰岛素过敏，对肥胖有抵抗力。然而，抵抗肥胖的分子基础尚不清楚。在这里，我们表明，PTP 1B调节瘦素信号。在转染研究中，PTP 1B使瘦素受体相关激酶Jak 2去磷酸化。PTP 1B在下丘脑区域中表达，该区域具有瘦素反应神经元。与野生型同窝小鼠相比，PTP 1B（-/-）小鼠具有降低的瘦素/体脂比、瘦素超敏性和增强的瘦素诱导的下丘脑Stat 3酪氨酰磷酸化。金硫代葡萄糖治疗，消除瘦素反应下丘脑神经元，部分克服PTP 1B（-/-）小鼠的肥胖抵抗力。我们的数据表明，PTP 1B在体内调节瘦素信号，可能是通过靶向Jak 2。PTP 1B可能是治疗肥胖症瘦素抵抗的新靶点。
Mice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin and resistant to obesity. However, the molecular basis for resistance to obesity has been unclear. Here we show that PTP1B regulates leptin signaling. In transfection studies, PTP1B dephosphorylates the leptin receptor-associated kinase, Jak2. PTP1B is expressed in hypothalamic regions harboring leptin-responsive neurons. Compared to wild-type littermates, PTP1B(-/-) mice have decreased leptin/body fat ratios, leptin hypersensitivity, and enhanced leptin-induced hypothalamic Stat3 tyrosyl phosphorylation. Gold thioglucose treatment, which ablates leptin-responsive hypothalamic neurons, partially overcomes resistance to obesity in PTP1B(-/-) mice. Our data indicate that PTP1B regulates leptin signaling in vivo, likely by targeting Jak2. PTP1B may be a novel target to treat leptin resistance in obesity.