Ming Ma1, Qi Long2, Fei Chen2, Ting Zhang2, Wenqiao Wang3. 1. Department of Clinical Nutrition, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 310052 Hangzhou, P.R, China. Electronic address: maming73@zju.edu.cn. 2. Department of Clinical Nutrition, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 310052 Hangzhou, P.R, China. 3. College of Public Health, Zhejiang University School of Medicine, Hangzhou, P.R., 310011, China.
Abstract
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) refers to an accumulation of excess fat in liver due to causes other than alcohol use. The relationship between vitamin D (VD) and NAFLD has been previously studied. Therefore, we aimed to explore the mechanism involved active VD regulating the progression of NAFLD by inhibiting cell senescence and to provide a potential approach for further nutritional treatment of NAFLD. METHODS: Following the induction with high-fat diet and intraperitoneal injection of corn oil, the successfully established NAFLD rat models were treated with 1,25(OH)2D3 at 1μg/kg, 5μg/kg or 10μg/kg. Meanwhile, the levels of factors related to oxidative stress, cell senescence, the p53-p21 signaling pathway and inflammation in liver were determined. Then, cell senescence was also measured by using senescence-associated β-galactosidase (SAβ-gal) staining. RESULTS: It was also found that active VD increased the concentration of VD in serum and VDR in liver of NAFLD rats, and alleviated hepatic fibrosis. Besides, treatment of 1,25(OH)2D3 at 1μg/kg, 5μg/kg or 10μg/kg reduced oxidative stress and inflammation, inhibited the p53-p21 signaling pathway and consequent cell senescence. Furthermore, treatment of 1,25(OH)2D3 at a dosage of 5μg/kg made the most impact on these factors. CONCLUSION: Collectively, the evidences from this study demonstrated that active VD could alleviate the development of NAFLD through blocking the p53-p21 signaling pathway, which provided a novel nutritional therapeutic insight for NAFLD.
OBJECTIVE:Non-alcoholic fatty liver disease (NAFLD) refers to an accumulation of excess fat in liver due to causes other than alcohol use. The relationship between vitamin D (VD) and NAFLD has been previously studied. Therefore, we aimed to explore the mechanism involved active VD regulating the progression of NAFLD by inhibiting cell senescence and to provide a potential approach for further nutritional treatment of NAFLD. METHODS: Following the induction with high-fat diet and intraperitoneal injection of corn oil, the successfully established NAFLD rat models were treated with 1,25(OH)2D3 at 1μg/kg, 5μg/kg or 10μg/kg. Meanwhile, the levels of factors related to oxidative stress, cell senescence, the p53-p21 signaling pathway and inflammation in liver were determined. Then, cell senescence was also measured by using senescence-associated β-galactosidase (SAβ-gal) staining. RESULTS: It was also found that active VD increased the concentration of VD in serum and VDR in liver of NAFLD rats, and alleviated hepatic fibrosis. Besides, treatment of 1,25(OH)2D3 at 1μg/kg, 5μg/kg or 10μg/kg reduced oxidative stress and inflammation, inhibited the p53-p21 signaling pathway and consequent cell senescence. Furthermore, treatment of 1,25(OH)2D3 at a dosage of 5μg/kg made the most impact on these factors. CONCLUSION: Collectively, the evidences from this study demonstrated that active VD could alleviate the development of NAFLD through blocking the p53-p21 signaling pathway, which provided a novel nutritional therapeutic insight for NAFLD.