The novel mechanism of recombinant human ciliary neurotrophic factor on the anti-diabetes activity.
In a previous study, the ciliary neurotrophic factor (CNTF) were demonstrated to lead to weight-loss partly by up-regulating the energy metabolism and the expression of uncoupling protein-1, mitochondrial transcription factor A and nuclear respiratory factor-1 in adipose tissues or muscle. To investigate the up-stream regulators of the expression, recombinant human CNTF (rhCNTF) (0.1, 0.3 and 0.9 mg/kg/day subcutaneously) were administered to KK-Ay mice for 30 days, resulting in reduction of perirenal fat mass, serum free fatty acids and islet triacylglycerol; furthermore, the values of oral glucose tolerance test were found improved. In brown adipose tissues, the gene expressions of peroxisome proliferator-activated receptor alpha (PPARalpha) and peroxisome proliferator-activated receptor coactivator-1 alpha (PGC-1alpha) were found to be up-regulated by rhCNTF. To the best of our knowledge, the changes of gene expression of PPARalpha and PGC-1alpha represent new insights into the mechanisms of anti-diabetes by rhCNTF. In addition, the activity of mitochondrial complexII was found to be increased by rhCNTF. Stimulation of PPARalpha, PGC-1alpha, uncoupling protein-1 and enhanced activity of mitochondrial complex II may be associated with the effects of anti-diabetes. The present study indicates new mechanisms of the activity and mechanisms on anti-diabetes of rhCNTF, which may be a novel anti-diabetes reagent partly acting by enhancing energy metabolism.
Liu
Qing-Shan
QS
China Pharmaceutical University, Nanjing, China.
Gao
Mei
M
Zhu
Shen-Yin
SY
Li
Shao-Jing
SJ
Zhang
Li
L
Wang
Qiu-Juan
QJ
Du
Guan-Hua
GH
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D047493:PPAR alpha / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology
D020934:Ciliary Neurotrophic Factor; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D011994:Recombinant Proteins