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

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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.

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Acknowledgments

The authors thank Dr Shan Lu for technical support in the animal studies.

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Authors and Affiliations

  1. 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

    Yan Zhou & Yongji Li

  2. Department of Rheumatology and Immunology, Wenzhou People’s Hospital, Wenzhou, China

    Suxian Lin

  3. Department of Rheumatology and Immunology, The Central Hospital of Wenzhou, Wenzhou, China

    Lihe Zhang

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  1. Yan Zhou
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Correspondence to Yongji Li.

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Zhou, Y., Lin, S., Zhang, L. et al. Resveratrol prevents renal lipotoxicity in high-fat diet-treated mouse model through regulating PPAR-α pathway. Mol Cell Biochem 411, 143–150 (2016). https://doi.org/10.1007/s11010-015-2576-y

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