Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China.
Department of Clinical Nutrition, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Front Endocrinol (Lausanne). 2023 Mar 22;14:1138078. doi: 10.3389/fendo.2023.1138078. eCollection 2023.
The study aimed to explore the association of serum 25(OH)D and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway.
The study contained a case-control study, and experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D and NAFLD. study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. , HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot.
NAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D. VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD.
The study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis the PPARα signaling pathway.
本研究旨在探讨血清 25(OH)D 与非酒精性脂肪性肝病 (NAFLD) 患者肝脂肪变性的关系，并确定维生素 D (VD) 的作用是否通过激活过氧化物酶体增殖物激活受体 α (PPARα) 通路来介导。
本研究包含病例对照研究和实验。病例对照研究比较了 NAFLD 患者和对照组的血清参数，并评估了 25(OH)D 与 NAFLD 的关系。实验中，雄性 Wistar 大鼠随机分为对照组和模型组，分别给予标准饲料和高脂饲料（HFD）喂养 7 周，建立 NAFLD 模型。然后，用 VD 和 PPARα 拮抗剂（MK886）处理大鼠 7 周。收集组织和血清，通过生化测定、形态分析、组织学分析和 Western blot 分析进行评估。此外，用油酸（OA）孵育 HepG2 细胞诱导脂肪变性，通过染色进行评估。用 MK886 预处理 HepG2 细胞，然后用骨化三醇处理，通过 Western blot 检测脂质代谢相关蛋白的差异。
NAFLD 患者表现为肝功能受损、血脂异常和胰岛素抵抗。血清 25(OH)D 与 NAFLD 患者的丙氨酸氨基转移酶（ALT）呈负相关。VD 缺乏是无晚期纤维化患者的危险因素。在调整混杂因素后，充足的 VD 状态（25(OH)D >20 ng/mL）对患者具有保护作用。NAFLD 大鼠表现为严重的肝脂肪变性、全身性炎症和血清 25(OH)D 降低的高脂血症。VD 治疗可改善 NAFLD 大鼠和 OA 诱导的 HepG2 细胞的肝脂肪变性。此外，MK886 抑制了 VD 的抗脂肪变性作用。
本研究表明，适当的 VD 水平可能是 NAFLD 的保护因素，VD 可能通过激活 PPARα 信号通路缓解肝脂肪变性。
