Adiponectin improves endothelial dysfunction caused by elevated FFAs levels, partially through cAMP-dependent pathway.

AIMS: To determine whether adiponectin can attenuate endothelial dysfunction caused by elevated free fatty acids (FFAs) concentration, and if so, to explore the underlying mechanism.

METHODS: Male Sprague-Dawley rat thoracic aortas were isolated then cut into four vascular rings, incubated in organ bath containing Krebs-Henseleit buffer with different agents separately: 800 μmol/L Palmic acid (FFA, n = 14), 800 μmol/L Palmic acid + 2 μg/mL adiponectin (FFA + gAd, n = 14), 800 μmol/L Palmic acid + 2 μg/mL adiponectin + 200 μmol/L adenylate cyclase inhibitor dideoxyadenosine (FFA + gAd + ddAdo, n = 7), blank control (NC, n=10). The endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIV) were assessed by acetylcholine (Ach) induced contraction of the aortas. Nuclear transcription factor kappa B (NF-κB) expression in rat aortic section was evaluated immunohistochemically.

RESULTS: Ach caused a concentration dependent vascular relaxation in all pre-constricted aortic rings. PA treatment impaired the Ach induced EDV which was significantly attenuated by pretreatment with adiponectin. Dideoxyadenosine partly abolished the vascular protective effect of adiponectin. Sodium nitroprusside (SNP) had no significant effect on the vasodilatation among four groups. Increased NF-κB expression was noted in FFA group. Pretreatment with adiponectin partly decreased NF-κB expression when compared with FFA group.

CONCLUSION: Adiponectin may independently mitigate endothelial dysfunction caused by elevated FFAs concentration through the cross talk between cAMP and NF-κB signaling pathway.