Bjørbaek C, Elmquist J K, Frantz J D, Shoelson S E, Flier J S
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Mol Cell. 1998 Mar;1(4):619-25. doi: 10.1016/s1097-2765(00)80062-3.
Leptin affects food intake and body weight by actions on the hypothalamus. Although leptin resistance is common in obesity, mechanisms have not been identified. We examined the effect of leptin on expression of the suppressors-of-cytokine-signaling (SOCS) family of proteins. Peripheral leptin administration to ob/ob, but not db/db mice, rapidly induced SOCS-3 mRNA in hypothalamus, but had no effect on CIS, SOCS-1, or SOCS-2. A leptin-dependent increase of SOCS-3 mRNA was seen in areas of hypothalamus expressing high levels of the leptin receptor long form. In mammalian cell lines, SOCS-3, but not CIS or SOCS-2, blocked leptin-induced signal transduction. Expression of SOCS-3 mRNA in the arcuate and dorsomedial hypothalamic nuclei is increased in Ay/a mice, a model of leptin-resistant murine obesity. In conclusion, SOCS-3 is a leptin-inducible inhibitor of leptin signaling, and a potential mediator of leptin resistance in obesity.
瘦素通过作用于下丘脑来影响食物摄取和体重。尽管瘦素抵抗在肥胖症中很常见，但其机制尚未明确。我们研究了瘦素对细胞因子信号抑制蛋白（SOCS）家族蛋白表达的影响。给ob/ob小鼠而非db/db小鼠外周注射瘦素，可迅速诱导下丘脑SOCS-3 mRNA的表达，但对CIS、SOCS-1或SOCS-2没有影响。在表达高水平瘦素受体长型的下丘脑区域，可观察到SOCS-3 mRNA的表达依赖于瘦素增加。在哺乳动物细胞系中，SOCS-3而非CIS或SOCS-2可阻断瘦素诱导的信号转导。在Ay/a小鼠（一种瘦素抵抗性小鼠肥胖模型）中，弓状核和下丘脑背内侧核中SOCS-3 mRNA的表达增加。总之，SOCS-3是一种瘦素诱导的瘦素信号转导抑制剂，可能是肥胖症中瘦素抵抗的介导因子。
