title: Resveratrol prevents renal lipotoxicity in high-fat diet-treated mouse model through regulating PPAR-α pathway.
abstract: 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.
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University, Fuxue Lane 2, Lucheng District, Wenzhou, 325015, Zhejiang, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Rheumatology and Immunology, Wenzhou People's Hospital, Wenzhou, China.
authors.forename: Suxian
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Rheumatology and Immunology, The Central Hospital of Wenzhou, Wenzhou, China.
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University, Fuxue Lane 2, Lucheng District, Wenzhou, 325015, Zhejiang, People's Republic of China. wzmulyj@163.com.
authors.forename: Yongji
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D047493:PPAR alpha / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D047493:PPAR alpha; D013267:Stilbenes; D000077185:Resveratrol
keywords: High-fat diet; Nephropathy; PPAR-α; Resveratrol