Strong evidence for significant systemic Axokine effects (in addition to centrally CNS) in obesity/TII diabetes.
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<<In summary, we observed that native as wells as cultured adipocytes are responsive to CNTF
treatment. Interestingly, CNTFRa is not highly expressed in cultured adipocytes, but readily detectable
in rodent adipose tissue and furthermore highly up regulated in multiple rodent models of obesity/type
II diabetes. This is the first demonstration that this receptor is expressed in adipose tissue and that it is
highly regulated in obesity/type II diabetes. Current studies are underway to determine the role of
CNTFRa in adipose tissue function and examine the ability of CNTF to act as insulin sensitizer in fat
and muscle.>>
J Biol Chem 2002 Nov 6;
The regulation and activation of CNTF signaling proteins in adipocytes.
Zvonic S, Cornelius P, Stewart WC, Mynatt RL, Stephens JM.
Biological Sciences, Louisiana State Univ., Baton Rouge, LA 70803.
CNTF is known for its roles as a lesion factor released by ruptured glial cells and prevents neuronal degeneration. However, CNTF has also been shown to cause weight loss in various rodent models of obesity/type II diabetes, while a modified form also causes weight loss in humans. CNTF administration can correct or improve hyperinsulinemia, hyperphagia, and hyperlipidemia associated with these models of obesity. To investigate the effects of CNTF on fat cells, we examined the expression of CNTF receptor complex proteins (LIFR, gp130, CNTFRalpha)during adipocyte differentiation and the effects of CNTF on STAT, Akt, and MAPK activation. We also examined the ability of CNTF to regulate the expression of adipocyte transcription factors and other adipogenic proteins. Our studies clearly demonstrate that the expression of two of the three CNTF receptor complex components, CNTFRalpha and LIFR, decreases during adipogenesis. In contrast, gp130 expression is relatively unaffected by differentiation. Also, preadipocytes are more sensitive to CNTF treatment than adipocytes, as judged by STAT 3 and Akt activation. Despite decreased levels of CNTFRalpha in 3T3-L1 adipocytes, CNTF treatment of these cells resulted in a time dependent activation of STAT 3. Chronic treatment of adipocytes resulted in a substantial decrease in FAS and a decline in SREBP-1 levels, but had no effect on the expression of PPARgamma, acrp 30, adipocyte expressed STAT proteins, or C/EBPalpha. However, CNTF resulted in a significant increase in IRS-1 expression. CNTFRalpha receptor expression was substantially induced in the fat pads of four rodent models of obesity/type II diabetes as compared to lean littermates. Moreover, we demonstrated that CNTF can activate STAT 3 in adipose tissue and skeletal muscle in vivo. In summary, CNTF effects adipocyte gene expression and the specific receptor for this cytokine is induced in rodent models of obesity/type II diabetes.
PMID: 12424252 [PubMed - as supplied by publisher] |
