Resveratrol prevents renal lipotoxicity in high-fat diet-treated mouse model through regulating PPAR-α pathway.

Zhou, Yan; Lin, Suxian; Zhang, Lihe; Li, Yongji

Resveratrol (RSV) has beneficial effects on renal diseases, but its underlying mechanisms are still unclear. In the present study, we investigate the renoprotective effects of RSV on obesity-related renal diseases and clarify the potential mechanisms. Male C57BL/6J mice were fed with high-fat diet (HFD) with or without 400 mg/kg RSV treatment for 12 weeks. Feeding HFD induced renal injuries, but treating them with RSV significantly decreased glomerular volume ( p < 0.05), glycogen ( p < 0.01) and collagen ( p < 0.05) in renal tissues. Although slightly changed body weight and fasting blood glucose, RSV attenuated renal dysfunction, including decreased levels of blood urea nitrogen ( p < 0.05), urea protein ( p < 0.01), and microalbuminuria ( p < 0.01). Furthermore, RSV treatment markedly reduced gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) (all p < 0.05), 4-Hydroxynonenal expression ( p < 0.01), and lipid accumulation. Mechanistically, RSV enhanced the expression of lipolytic genes, peroxisome proliferator-activated receptor (PPAR)-α ( p < 0.001), carnitine palmitoyltransferase (CPT)-1 ( p < 0.05), and medium-chain acyl-coenzyme A dehydrogenase (MCAD) ( p < 0.01), but had no effect on lipogenic genes, PPAR-γ and sterol regulatory element-binding protein (SREBP)-1c. RSV also obviously increased renal PPAR-α protein expression ( p < 0.001) and the phosphorylation of AMPK level. Collectively, these results support the therapeutic effects of RSV on high-fat diet-induced renal damages at least partially through targeting on PPAR-α signaling pathway.

PHYSIOLOGICAL effects of resveratrol; KIDNEY diseases; OBESITY complications; HIGH-fat diet; GENE expression; TUMOR necrosis factors; INTERLEUKIN-6; NITRIC-oxide synthases

Molecular & Cellular Biochemistry, 2015, Vol 411, Issue 1/2, p143

0300-8177

Academic Journal

10.1007/s11010-015-2576-y