Figure 8. Potential signaling pathways underlying the inhibitory effect of GCM on hepatocyte lipoapoptosis.

Lipid metabolic disorder impairs the basal autophagy, leading to activation of ER stress-JNK-mitochondrial pathway. In the presence of GCM, the impaired autophagy is reactivated and subsequently the activated ER stress and its downstream events are inhibited. In addition, GSK-3 is activated by lipid metabolic disorder, which also contributes to activation of JNK-mitochondrial pathway. These events are suppressed by GCM. Together, GCM protects against hepatocyte lipoapoptosis via activation of autophagy and inhibition of ER stress/GSK-3-JNK-mitochondial cascade.