非酒精性脂肪肝病（NAFLD）是肝脏发病率和死亡率最常见的原因之一，其病因机制多不明确。维生素D缺乏与NAFLD的发生率和严重程度增加有关。肝脏3-巯基丙酮硫转移酶（MPST）的表达增加和肝细胞凋亡失调参与了NAFLD的病理发生过程。我们旨在探索1,25-二羟基胆骨化醇（1,25-(OH)2 D3）对NAFLD发展的保护作用和可能的机制，包括肝脏MPST和caspase-3表达。60只雄性成年大鼠分为4周饲喂组和12周饲喂组，每组分为对照组、高脂饮食（HFD）组和HFD+VD组。测量了血清中的脂质谱参数、肝酶、胰岛素、葡萄糖、C-反应蛋白（CRP）、肿瘤坏死因子 (TNF-α) 和肝中丙二醛 (MDA)、总抗氧化能力（TAC）和反应性氧化物 (ROS) 含量。计算了BMI和HOMA-IR，并对肝组织进行了组织病理学和免疫组化研究。本研究发现，1,25-(OH)2D3显著降低了BMI、HOMA-IR、血清中葡萄糖、胰岛素、肝酶、脂质谱参数、CRP、TNF-α、肝中MDA、ROS、肝脏MPST、TNF-α、8-羟基-2'-脱氧鸟苷（8-OHdG）和caspase-3的表达，并显著增加了两个HFD饲料组的肝脏TAC。总之，1,25-(OH)2D3与HFD一起给药可消除4周组中与HFD相关的NAFLD变化，并显著减轻12周组中的变化。通过降低caspase-3和MPST表达的抗凋亡作用是本研究建议的新机制，这些机制可能涉及1,25-(OH)2D3的保护作用。© 2023年。作者，独家许可Springer Nature B.V.

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of liver morbidity and mortality and has multiple unclear pathogenic mechanisms. Vitamin D deficiency was associated with increased incidence and severity of NAFLD. Increased hepatic expression of 3-mercaptopyruvate sulfur transferase (MPST) and dysregulated hepatocyte apoptosis were involved in NAFLD pathogenesis. We aimed to explore the protective effect of 1,25-Dihydroxycholecalciferol (1,25-(OH)2 D3) against development of NAFLD and the possible underlying mechanisms, regarding hepatic MPST and caspase-3 expression. 60 male adult rats were divided into 4 and 12 week fed groups; each was subdivided into control, high-fat diet (HFD), and HFD + VD. Serum levels of lipid profile parameters, liver enzymes, insulin, glucose, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and hepatic levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and reactive oxygen species (ROS) were measured. BMI and HOMA-IR were calculated, and liver tissues were processed for histopathological and immunohistochemical studies. The present study found that 1,25-(OH)2 D3 significantly decreased BMI, HOMA-IR, serum levels of glucose, insulin, liver enzymes, lipid profile parameters, CRP, TNF-α, hepatic levels of MDA, ROS, hepatic expression of MPST, TNF-α, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and caspase-3; and significantly increased hepatic TAC in both HFD-fed groups. In conclusion: Administration of 1,25-(OH)2 D3 with HFD abolished the NAFLD changes associated with HFD in 4-week group, and markedly attenuated the changes in 12-week group. The anti-apoptotic effect via decrement of caspase-3 and MPST expression are novel mechanisms suggested to be implicated in the protective effect of 1,25-(OH)2 D3.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.