PMID- 22198805
OWN - NLM
STAT- MEDLINE
DCOM- 20120827
LR  - 20211021
IS  - 1432-136X (Electronic)
IS  - 0174-1578 (Linking)
VI  - 182
IP  - 4
DP  - 2012 May
TI  - Seasonal leptin resistance is associated with impaired signalling via JAK2-STAT3 
      but not ERK, possibly mediated by reduced hypothalamic GRB2 protein.
PG  - 553-67
LID - 10.1007/s00360-011-0637-4 [doi]
AB  - The Siberian hamster, Phodopus sungorus, undergoes a striking seasonal cycle of 
      leptin sensitivity and body weight regulation, but the molecular mechanism and 
      relevance to human leptin insensitivity are unknown. Here we show that nuclear 
      translocation of phospho-STAT3 in the hypothalamus is rapidly stimulated by 
      leptin to a greater extent in hamsters held in short-day length (SD) as compared 
      to long-day length (LD). Intriguingly, effects of leptin on STAT3 appeared to be 
      in part limited to nuclear translocation of phospho-STAT3 associated with the 
      cell surface rather than phosphorylation of STAT3. The number of phospho-ERK 
      cells within the hypothalamus was unaffected by either photoperiod or leptin. 
      However, proximal to ERK phosphorylation, hypothalamic SH2-containing tyrosine 
      phosphatase (SHP2) and the small growth factor receptor-binding protein (GRB2), 
      which act as competitive negative modulators on binding of SOCS3 to leptin 
      receptor (LRb)-associated Tyr(9)(8)(5), were increased in SD compared to LD. Our 
      findings suggest that activation of STAT3 by leptin may be dependent on 
      interaction of stimulatory SHP2/GRB2 as well as inhibitory SOCS3 on the level of 
      competitive binding to LRb-associated Tyr(9)(8)(5). This hypothetical mechanism may 
      represent the molecular identity of seasonally induced adjustments in leptin 
      sensitivity and may be applied to investigating leptin sensitivity in other 
      rodent models.
FAU - Tups, Alexander
AU  - Tups A
AD  - Department of Animal Physiology, Faculty of Biology, Philipps University Marburg, 
      Marburg, Germany. tups@staff.uni-marburg.de
FAU - Stohr, Sigrid
AU  - Stohr S
FAU - Helwig, Michael
AU  - Helwig M
FAU - Barrett, Perry
AU  - Barrett P
FAU - Krol, Elzbieta
AU  - Krol E
FAU - Schachtner, Joachim
AU  - Schachtner J
FAU - Mercer, Julian G
AU  - Mercer JG
FAU - Klingenspor, Martin
AU  - Klingenspor M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111224
PL  - Germany
TA  - J Comp Physiol B
JT  - Journal of comparative physiology. B, Biochemical, systemic, and environmental 
      physiology
JID - 8413200
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Leptin)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Leptin)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
SB  - IM
MH  - Animals
MH  - Cell Nucleus
MH  - Cricetinae
MH  - Female
MH  - GRB2 Adaptor Protein/*metabolism
MH  - Gene Expression Regulation
MH  - Hypothalamus/cytology/*metabolism
MH  - Janus Kinase 2/*metabolism
MH  - Leptin/*metabolism
MH  - Male
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neurons/cytology/metabolism
MH  - Phodopus/*metabolism
MH  - Photoperiod
MH  - Protein Isoforms/metabolism
MH  - Protein Transport
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Leptin/metabolism
MH  - STAT3 Transcription Factor/genetics/*metabolism
MH  - *Signal Transduction
MH  - Suppressor of Cytokine Signaling Proteins/metabolism
EDAT- 2011/12/27 06:00
MHDA- 2012/08/28 06:00
CRDT- 2011/12/27 06:00
PHST- 2011/09/23 00:00 [received]
PHST- 2011/11/27 00:00 [accepted]
PHST- 2011/11/25 00:00 [revised]
PHST- 2011/12/27 06:00 [entrez]
PHST- 2011/12/27 06:00 [pubmed]
PHST- 2012/08/28 06:00 [medline]
AID - 10.1007/s00360-011-0637-4 [doi]
PST - ppublish
SO  - J Comp Physiol B. 2012 May;182(4):553-67. doi: 10.1007/s00360-011-0637-4. Epub 
      2011 Dec 24.