https://pubmed.ncbi.nlm.nih.gov/31810868/ NAFLD

Clin Res Hepatol Gastroenterol. 2020 Sep;44(4):513-523.

Active vitamin D impedes the progression of non-alcoholic fatty liver disease by inhibiting cell senescence in a rat model

Ming Ma 1, Qi Long 2, Fei Chen 2, Ting Zhang 2, Wenqiao Wang 2
PMID: 31810868

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.

Keywords: Active vitamin D; Cell senescence; Non-alcoholic fatty liver disease; Oxidative stress; P53-p21 signaling pathway; Vitamin D receptor.