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. 2007 Apr 2;117(4):841–849. doi: 10.1172/JCI30453

Figure 3. Pathways by which CNTF acts as an antiobesogenic and insulin-sensitizing agent.

Figure 3

CNTF or other gp130R ligands can act in the CNS by signaling through the gp130R in POMC neurons in the hypothalamus to decrease AMPK and also by promoting neurogenesis in the arcuate nuclei. In the brain, CNTF/gp130Rβ ligands can also reduce neuropeptide Y (NPY) gene expression. These actions result in a decrease in food intake. In the periphery, gp130R ligands can increase lipid oxidation, thereby preventing steatosis in the liver and lipid accumulation in the muscle. The enhanced fat oxidation in these tissues and resultant decrease in accumulation of deleterious lipid species (diacylglyceride [DAG] and ceramide) prevent the activation of inflammatory serine threonine kinase cascades (JNK and Iκ kinase) in the liver and muscle and the transcription of Stearoyl-CoA desaturase (SCD-1) in liver to ameliorate lipid-induced decreases in insulin signal transduction. Although speculative, in skeletal muscle, these actions appear to be mediated by activation of AMPK, which may also lead to activation of PGC-1α. AgRP, agouti-related protein.