Peroxisome proliferator-activated receptor delta protects against obesity-related glomerulopathy through the P38 MAPK pathway

Authors

  • Zhencheng Yan,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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    • Discloure: The authors declare that no conflict of interest exists. Additional Supporting Information may be found in the online version of this article.

  • Yinxing Ni,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Peijian Wang,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Jian Chen,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Hongbo He,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Jing Sun,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Tingbing Cao,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Jing Chen,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Zhigang Zhao,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Zhidan Luo,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Lin Chen,

    1. State Key Lab Trauma Burns & Combined Injury, Center for Trauma, Institute of Surgery Research, Daping Hospital, Institute for Surgery Research, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China
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  • Daoyan Liu,

    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
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  • Zhiming Zhu

    Corresponding author
    1. Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China
    • Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China

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Abstract

Objective:

Obesity is a prominent component of metabolic syndrome and a major risk factor for renal disease. The aim of this study was to explore the effect of cross-talk between peroxisome proliferator-activated receptor (PPAR)δ and p38 mitogen-activated protein kinase (p38 MAPK) on obesity-related glomerulopathy.

Design and Methods:

Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet for 32 weeks. Glomerular mesangial cells HBZY-1 and mature differentiation 3T3-L1 cells were cocultured and were transfected with PPARδ-expressing vectors or treated with agonist or inhibitor of PPARδ or p38 MAPK.

Results:

Rats on a high-fat diet showed typical characteristics of metabolic syndrome including obesity, dyslipidemia, insulin resistance, and hypertension. Rats on a high-fat diet also had significant glomerular hypertrophy and extracellular matrix accumulation, which were accompanied by increased p38 MAPK phosphorylation and decreased PPARδ expression in the kidney tissue. The roles of p38 MAPK and PPARδ in a coculture system of mesangial cells and mature differentiation 3T3-L1 cells were further explored. PPARδ suppression promoted laminin and type IV collagen secretion through p38 MAPK phosphorylation in mesangial cells, whereas PPARδ overexpression or PPARδ agonist attenuated phosphorylation of p38 MAPK and laminin and type IV collagen secretion.

Conclusions:

The characteristics of obesity-related glomerulopathy, which might be partly caused by PPARδ suppression-induced p38 MAPK activation and laminin and type IV collagen secretion was demonstrated.

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