Leptin treatment increases suppressors of cytokine signaling in central and peripheral tissues

FEBS Letters

Emilsson, Valur²  de Groot, Rolf P.³  Arch, Jonathan R.S.¹  Cawthorne, Michael A.²  Lister, Carolyn A.¹ 

[1]SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK

[2]Clore Laboratory, University of Buckingham, Hunter Street, Buckingham, UK

[3]Department of Pulmonary Diseases, University Hospital Utrecht, Utrecht, The Netherlands

关键词: Leptin;    Signal transducer and activator of transcription;    Suppressor of cytokine signaling;    Cytokine-inducible SH2-containing protein;    Leptin resistance;    OB-R;    leptin receptor;    STAT;    signal transducers and activators of transcription;    SOCS;    suppressors of cytokine signaling;    CIS;    cytokine-inducible SH2-containing protein;    i.p.;    intraperitoneal;    RT-PCR;    reverse transcription-polymerase chain reaction;    GAS;    interferon-γ-activated sequence;    IRE;    interferon-γ/interleukin-6 response element;   

DOI  :  10.1016/S0014-5793(99)00874-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown