The role of leptin in obesity induced nitrooxidative stress and endothelial dysfunction – nanomedical approach
Keywords:
obesity, leptin, endothelial dysfunction, nitric oxide, superoxide, peroxynitriteAbstract
Hyperleptinemia accompanying obesity affects endothelial NO and is a serious factor for vascular disorders. NO, O2-, and ONOO- levels in HUVECs and aortic endothelium of obese mice were recorded using tandem electrochemical nanosensors. 12-h exposure of HUVECs to leptin increased eNOS expression and decreased the [NO]/[ONOO-] ratio. In obese mice, a 2.5-fold increase in leptin concentration coincided with 100% increase in eNOS and about 30% decrease in intracellular L-arginine. This led to eNOS uncoupling, a reduction in bioavailable NO, and an elevated concentration of O2- and ONOO-. L-Arginine supplementation reversed eNOS uncoupling and partially restored [NO]/[ONOO-] balance in obese mice.
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