Table 6 The description of the three signaling pathways related to occurrence and development of NAFLD
Signaling pathway | Target or metabolism | Activation or inhibition | Effect | Notes |
|---|---|---|---|---|
Prolactin signaling pathway | Prolactin | Activation | NAFLD ↓ | -Prolactin is an endogenous polypeptide with approximately 23 kda, which has negative relationships concerning NAFLD [66] -Prolactin receptor expression is diminished in obese subjects under NAFLD, the downregulation of which exacerbates NAFLD [66] -Thus, it implies that activation of prolactin signaling pathway can be a therapeutic strategy against NAFLD |
T cell receptor signaling pathway | Complex (MHC) class I (CD8 +) | Inhibition | NAFLD ↑ | -In NAFLD, reduction of CD8 + diminished the liver inflammation and led to hepatic stellate cell (HSC) inactivation [67] |
|  | Complex (MHC) class II (CD4 +) | Inhibition | NAFLD ↓ | -The dysfunction of lipid metabolism in NAFLD subjects (human and mouse) caused the reduction of CD4 + in liver [68, 69] -It has been implicated that CD4 + T cells decrease in the development of NAFLD while CD8 + T cells escalate in progression of HCC initiated by NAFLD [68, 70] |
PI3K-Akt signaling pathway | The synthesis of free fatty acids (FFAs) in organs | Inhibition | NAFLD ↓ | -In obese subjects, over-circulating of FFAs driven by PI3K-Akt signaling pathway can influence on negative side effects to organs, resulting in imbalance of glucose and lipid metabolism [71] |
|  | The synthesis of triglyceride in hepatocytes | Inhibition | NAFLD ↓ | -The up-regulation of PI3K-Akt signaling pathway accelerates the synthesis of triglyceride in hepatocytes [72] |