Role of Adiponectin in Central Nervous System Disorders

Figure 2

Proposed signaling mechanisms of adiponectin in prevention of ischemic stroke. Signaling through AdipoR1 and AdipoR2 can reduce formation of atheroma. AdipoR1 activates the AMP-activated protein kinase (AMPK) pathway resulting in phosphorylation of protein kinase B (Akt) and activation of vascular endothelial growth factor (VEGF). Activation of Akt through calcium calmodulin kinase kinase (CAMKK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and AMPK contributes to activation of endothelial nitric oxide synthase (eNOS). Additionally, AMPK and VEGF also increase eNOS activity leading to nitric oxide (NO) production. Increase in production of NO leads to vasodilation, which is beneficial in prevention of atheroma and ischemia. Adiponectin signaling reduces vascular cell adhesion molecule 1 (VCAM-1) and intracellular adhesion molecule 1 (ICAM-1), and these adhesion molecules increase atheroma size. Peroxisome proliferator-activated receptor alpha (PPARα) also reduces VCAM-1 and ICAM-1, and PPARα is activated by AdipoR2 signaling. PPARγ increases production of adiponectin and also leads to reduction of VCAM-1 and ICAM-1. This figure was produced using Servier Medical Art (http://www.servier.com/).