The Novel Mechanism of Recombinant Human Ciliary Neurotrophic Factor on the Anti-diabetes Activity

Authors: Liu, Qing-Shan1; Gao, Mei2; Zhu, Shen-Yin; Li, Shao-Jing2; Zhang, Li2; Wang, Qiu-Juan; Du, Guan-Hua

Source: Basic & Clinical Pharmacology & Toxicology, Volume 101, Number 2, August 2007 , pp. 78-84(7)

Publisher: Blackwell Publishing

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Abstract:

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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 α (PPARα) and peroxisome proliferator-activated receptor coactivator-1 α (PGC-1α) were found to be up-regulated by rhCNTF. To the best of our knowledge, the changes of gene expression of PPARα and PGC-1α 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 PPARα, PGC-1α, 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.

Document Type: Research article

DOI: 10.1111/j.1742-7843.2007.00092.x

Affiliations: 1: China Pharmaceutical University, Nanjing, 2: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and

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