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

• Published in: Basic & clinical pharmacology & toxicology Vol. 101; no. 2; pp. 78 - 84
• Main Authors: Liu, Qing‐Shan, Gao, Mei, Zhu, Shen‐Yin, Li, Shao‐Jing, Zhang, Li, Wang, Qiu‐Juan, Du, Guan‐Hua
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.08.2007; Blackwell
• Subjects: Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Animals; Biological and medical sciences; Ciliary Neurotrophic Factor - pharmacology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Acids, Nonesterified - blood; Female; Humans; Hypoglycemic Agents - pharmacology; Male; Medical sciences; Mice; Mice, Obese; Pharmacology. Drug treatments; PPAR alpha - drug effects; PPAR alpha - genetics; Recombinant Proteins - pharmacology; Endocrinopathy; Human; Diabetes mellitus; Recombinant protein; Ciliary neurotrophic factor; Mechanism of action; Biological activity
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2007.00092.x

:  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.