Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, Rion, 26504 Patras, Greece.
Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece.
Int J Mol Sci. 2023 May 5;24(9):8288. doi: 10.3390/ijms24098288.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with increasing prevalence worldwide. The genetic and molecular background of NAFLD pathogenesis is not yet clear. The vitamin D/vitamin D receptor (VDR) axis is significantly associated with the development and progression of NAFLD. Gene polymorphisms may influence the regulation of the VDR gene, although their biological significance remains to be elucidated. VDR gene polymorphisms are associated with the presence and severity of NAFLD, as they may influence the regulation of adipose tissue activity, fibrosis, and hepatocellular carcinoma (HCC) development. Vitamin D binds to the hepatic VDR to exert its biological functions, either by activating VDR transcriptional activity to regulate gene expression associated with inflammation and fibrosis or by inducing intracellular signal transduction through VDR-mediated activation of Ca channels. VDR activity has protective and detrimental effects on hepatic steatosis, a characteristic feature of NAFLD. Vitamin D-VDR signaling may control the progression of NAFLD by regulating immune responses, lipotoxicity, and fibrogenesis. Elucidation of the genetic and molecular background of VDR in the pathophysiology of NAFLD will provide new therapeutic targets for this disease through the development of VDR agonists, which already showed promising results in vivo.
非酒精性脂肪性肝病 (NAFLD) 是最常见的慢性肝病，全球患病率呈上升趋势。NAFLD 发病机制的遗传和分子背景尚不清楚。维生素 D/维生素 D 受体 (VDR) 轴与 NAFLD 的发生和发展显著相关。基因多态性可能影响 VDR 基因的调控，尽管其生物学意义仍有待阐明。VDR 基因多态性与 NAFLD 的存在和严重程度相关，因为它们可能影响脂肪组织活性、纤维化和肝细胞癌 (HCC) 发展的调节。维生素 D 与肝脏 VDR 结合发挥其生物学功能，通过激活 VDR 转录活性来调节与炎症和纤维化相关的基因表达，或通过 VDR 介导的 Ca 通道激活诱导细胞内信号转导。VDR 活性对非酒精性脂肪性肝病的特征性特征——肝脂肪变性具有保护和有害作用。维生素 D-VDR 信号可能通过调节免疫反应、脂毒性和纤维化来控制 NAFLD 的进展。阐明 VDR 在 NAFLD 病理生理学中的遗传和分子背景将通过开发 VDR 激动剂为这种疾病提供新的治疗靶点，VDR 激动剂在体内已显示出有希望的结果。
