High FFA levels related to microalbuminuria and uncoupling of VEGF-NO axis in obese rats

Abstract

Purpose: The objectives of this study were to test whether elevated free fatty acids (FFA) from visceral fat accumulation is related to increased urinary albumin excretion and whether fenofibrate has renal protective effects by regulating vascular endothelial growth factor-nitric oxide (VEGF-NO) axis in rats with diet-induced obesity.

Methods: Wistar rats were randomly divided into groups fed a normal diet, a high-fat diet, and a high-fat diet plus fenofibrate. Blood and urine samples were collected. Endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV) of the aorta. Renal tissues were collected for CD31 immunohistochemistry. Glomerular NO and VEGF expression were measured by Griess reaction and Western blot, respectively.

Results: At the end of 24 weeks, plasma FFA and triglyceride levels significantly increased in the obese rats. Fenofibrate intervention decreased serum FFA and triglyceride levels by 43.4 and 48 %, respectively, accompanied by a reduced visceral fat index. Urinary albumin/creatinine ratio increased in obese rats, which decreased 62.6 % after fenofibrate intervention. Severe EDV impairment was observed in obese rats; this was partially improved by fenofibrate. CD31 expression in glomeruli increased in obese rats, indicating increased endothelial cell proliferation. Obese rats showed increased glomerular VEGF expression and reduced NO levels. This uncoupling of VEGF-NO axis was partially improved by fenofibrate.

Conclusion: Elevated circulating FFA level may cause increased microalbuminuria in obese rats due to impairment of EDV; increased microalbuminuria can be improved by fenofibrate intervention. The mechanism may be related to FFA-induced uncoupling of VEGF-NO axis and endothelial dysfunction.