Identification of SOCS-3 as a potential mediator of central leptin resistance

被引：727

作者：

Bjorbaek, C

Elmquist, JK

Frantz, JD

Shoelson, SE

Flier, JS ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA

[3] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02215 USA

[4] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA

[5] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA

来源：

MOLECULAR CELL | 1998年 / 1卷 / 04期

关键词：

D O I：

10.1016/S1097-2765(00)80062-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-5. A leptin-dependent increase of SCCS-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 A(y)/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.

引用

页码：619 / 625

页数：7

共 47 条

[1] Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of cytokine receptor signaling [J].