Objective: To investigate whether rosiglitazone has renal protective effects in diet-induced obese rats.

Methods: Wistar rats were randomly divided into normal control (NC), obesity (OB) and rosiglitazone (OB + R) group (n = 8 in each group). The NC group was fed with normal diet. The OB and OB + R groups were fed with high-fat diet. Four weeks later, rosiglitazone [4 mg/(kg x d)] was given to the OB + R group by oral gavage. The other two groups were given the same amount of physiological saline in the same manner. After 24 weeks, urinary albumin/creatinine ratio (ACR) was measured. Endothelial function was determined by measuring vasodilatation of aorta. Renal tissues were collected for morphological and CD31 immunohistochemistry. Glomerular vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels were measured.

Results: Body weight, visceral fat, plasma free fatty acids (FFAs), plasma triglyceride and ACR levels increased significantly in the obese rats (P < 0.01). Rosiglitazone intervention decreased visceral fat, plasma FFAs, plasma triglyceride and ACR levels (P< 0.01), which were still higher than NC group (P < 0.01). ACR levels of the OB group were higher than those of NC group (P < 0.01), while those of OB + R group were lower than those in OB group (P < 0.01), but still higher than those of NC group (P < 0.05). Endothelium-dependent vasodilatation was impaired in the obese rats. Rosiglitazone intervention could enhance acetylcholine-induced vasorelaxation and improved endothelium-dependent vasodilatation (P < 0.05), which was similar to that in NC group (P > 0.05). Morphological and immunohistochemistry results showed glomerulomegalia, increased glomerular CD31 expression and increased proliferation of glomerular endothelial cells, which were improved by rosiglitazone (P < 0.05). Obese rats showed increased glomerular VEGF and reduced NO levels (P < 0.05). This imbalance of VEGF/NO was partly improved by rosiglitazone intervention (P < 0.05).

Conclusion: Rosiglitazone reduces urinary albumin excretion and has renal protective effects by improving the imbalance of VEGF/NO and endothelial dysfunction in diet-induced obese rats.