Manyu Luo1,2, Ping Luo1, Zhiguo Zhang2,3, Kristen Payne2,4, Sara Watson2,5, Hao Wu1,2, Yi Tan2, Yushuang Ding1, Weixia Sun2,3, Xinmin Yin6, Xiang Zhang6, Gilbert Liu2, Kupper Wintergerst2,5, Lining Miao1, Lu Cai2,5. 1. Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin, China. 2. Department of Pediatrics, The University of Louisville, Kentucky, USA. 3. The First Hospital of Jilin University, Changchun, Jilin, China. 4. Department of Internal Medicine, The Marshall University Joan C. Edwards School of Medicine, Huntington, West Virginia, USA. 5. Wendy L. Novak Diabetes Care Center, The University of Louisville School of Medicine, Kentucky, USA. 6. Department of Chemistry, The University of Louisville, Kentucky, USA.
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.
OBJECTIVE:Obesity, particularly childobesity, 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 Znmarginal 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.
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