Emilsson V, Arch J R, de Groot R P, Lister C A, Cawthorne M A
Clore Laboratory, University of Buckingham, UK.
FEBS Lett. 1999 Jul 16;455(1-2):170-4. doi: 10.1016/s0014-5793(99)00874-1.
Leptin concentrations are elevated in the majority of obese individuals raising the possibility that leptin resistance contributes to their obesity. Peripheral leptin administration for 48 h caused a several-fold increase in mRNA encoding the suppressors of cytokine signaling SOCS-3 and CIS in hypothalamus and peripheral tissues. Paradoxically, CIS and SOCS-3 mRNAs are also elevated in the leptin-deficient ob/ob mouse. Forced expression of CIS in insulinoma cells prevented transactivation mediated by leptin. Thus tissues continuously exposed to leptin and/or other factors associated with obesity accumulate excessive amounts of SOCS-3 and CIS which could provide a potential mechanism for leptin resistance.
大多数肥胖个体的瘦素浓度升高，这增加了瘦素抵抗导致其肥胖的可能性。外周给予瘦素48小时会导致下丘脑和外周组织中编码细胞因子信号抑制因子SOCS-3和CIS的mRNA增加数倍。矛盾的是，瘦素缺乏的ob/ob小鼠中CIS和SOCS-3 mRNA也升高。在胰岛素瘤细胞中强制表达CIS可阻止瘦素介导的反式激活。因此，持续暴露于瘦素和/或与肥胖相关的其他因素的组织会积累过量的SOCS-3和CIS，这可能为瘦素抵抗提供一种潜在机制。
