Leptin treatment increases suppressors of cytokine signaling in central and peripheral tissues.
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.
Emilsson
V
V
Clore Laboratory, University of Buckingham, UK. valur.emilsson@buckingham.ac.uk
Arch
J R
JR
de Groot
R P
RP
Lister
C A
CA
Cawthorne
M A
MA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors
D017931:DNA Primers; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors