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.