Zinc delays the progression of obesity-related glomerulopathy in mice via down-regulating P38 MAPK-mediated inflammation

Manyu Luo, Ping Luo, Zhiguo Zhang, Kristen Payne, Sara Watson, Hao Wu, Yi Tan, Yushuang Ding, Weixia Sun, Xinmin Yin, Xiang Zhang, Gilbert Liu, Kupper Wintergerst, Lining Miao, Lu Cai

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Objective: Obesity, particularly child obesity, is one of the most common public health problems in the world and raises the risk of end-stage renal disease. Zinc (Zn) is essential for multiple organs in terms of normal structure and function; however, effects of Zn deficiency or supplementation among young individuals with obesity have not been well studied. Methods: Weaned mice were fed high-fat diets (HFD) with varied contents of Zn (Zn deficient, adequate, and supplemented) for 3 or 6 months. This study examined associations between renal pathogenesis and dietary Zn levels, specifically assessing inflammatory pathways by utilizing P38 MAPK inhibitor SB203580. Results: HFD feeding induced typical syndromes of obesity-related renal disorders, which worsened by Zn marginal deficiency. The progression of obesity-related renal disorders was delayed by Zn supplementation. HFD induced renal inflammation, reflected by increased P38 MAPK phosphorylation along with increases of inflammatory cytokines MCP-1, IL-1β, IL-6, and TNF-α. P38 MAPK inhibition prevented renal pathological changes in mice fed with HFD and HFD/Zn deficiency. Conclusions: P38 MAPK mediated the renal inflammatory responses, which played a central role in the pathogenesis of HFD-induced renal disorders. Zn could delay the progression of obesity-related kidney disease by down-regulating P38 MAPK-mediated inflammation.

Original languageEnglish (US)
Pages (from-to)1244-1256
Number of pages13
JournalObesity
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2016

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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    Luo, M., Luo, P., Zhang, Z., Payne, K., Watson, S., Wu, H., Tan, Y., Ding, Y., Sun, W., Yin, X., Zhang, X., Liu, G., Wintergerst, K., Miao, L., & Cai, L. (2016). Zinc delays the progression of obesity-related glomerulopathy in mice via down-regulating P38 MAPK-mediated inflammation. Obesity, 24(6), 1244-1256. https://doi.org/10.1002/oby.21463