Recombinant human ciliary neurotrophic factor reduces weight partly by regulating nuclear respiratory factor 1 and mitochondrial transcription factor A.
Ciliary neurotrophic factor (CNTF) can lead to weight loss by up-regulating energy metabolism and the expression of UCP-1 in mitochondria. To investigate the up-stream regulators of the expression of UCP-1, recombinant human CNTF (rhCNTF) (0.1, 0.3, 0.9 mg/kg/day s.c.) administered to KK-Ay mice for 30 days resulting in reductions in body weight and perirenal fat mass. In brown adipose tissues, the gene expressions of nuclear respiratory factor (NRF)-1, mitochondrial transcription factor A (TFam) and uncoupling protein (UCP)-1 were found up-regulated by rhCNTF. To the best of our knowledge, these effects represent new insights on the mechanisms of action of weight loss by rhCNTF. In addition, we also found that rhCNTF increased the activity of mitochondrial complex IV. The stimulation of NRF-1, TFam, UCP-1 and the enhanced activity of mitochondrial complex IV may be associated with remedying obesity. The result indicates that rhCNTF can enhance the expressions of NRF-1 and TFam, both of which can up-regulate the expression of UCP-1.
Liu
Qing-Shan
QS
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009 PR China.
Wang
Qiu-Juan
QJ
Du
Guan-Hua
GH
Zhu
Shen-Yin
SY
Gao
Mei
M
Zhang
Li
L
Zhu
Jun-Ming
JM
Cao
Jian-Feng
JF
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D019440:Anti-Obesity Agents / Q000378:metabolism* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008820:Mice, Obese; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
D019440:Anti-Obesity Agents; D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D012333:RNA, Messenger; D014157:Transcription Factors; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C422562:mitochondrial transcription factor A; D045304:Cytochromes c; C118937:axokine; D003576:Electron Transport Complex IV