Hu Zhengyu, Li Yan, Ma Bingwei, Lei Saifei, Wang Xingchun
Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, China.
Department of Gastroenterology, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, China.
Front Nutr. 2022 Sep 8;9:952056. doi: 10.3389/fnut.2022.952056. eCollection 2022.
Vitamin C (Vit C) and iron metabolism are closely related to metabolic disorders. However, the relation between iron storage protein ferritin and Vit C has not been elucidated. We aimed to investigate the crosstalk between Vit C and ferritin and its implications on non-alcoholic fatty liver disease (NAFLD). Clinical information of 3,614 subjects was obtained from the NHANES Public Data 2017-2018. FibroScan data, which estimates liver steatosis and fibrosis and Vit C, were selected to assess factors influencing NAFLD in this cross-sectional study. Ferritin and Vit C among different categories of liver steatosis and fibrosis were assessed by CAP and E value. Logistic regression and RCS models were used to analyze the correlations. study in hepG2 were conducted to validate the regulations. Ferritin increased while Vit C decreased with more severe hepatic steatosis and hepatic fibrosis (all < 0.001). Logistic regression models indicated that increased serum ferritin was a risk factor for NAFLD while increased Vit C was a protective factor for NAFLD and hepatic fibrosis after adjusting the continuous and categorical variables. Vitamin C was negatively associated with ferritin. Further mediation analysis identified that ferritin mediates the impact of Vit C on NAFLD ( < 0.05) and cirrhosis ( < 0.001). The experiments on cellular level suggested Vit C alleviated PA/OA induced steatosis and maintains iron homeostasis through inhibiting PA/OA induced upregulation of iron bound protein ferritin and labile iron pool (LIP) induction in hepG2 cells. In conclusion, Vit C was a protective factor, whereas ferritin was a risk factor for hepatic steatosis and fibrosis. Vitamin C alleviated NAFLD and maintained iron homeostasis via ferritin suppression and LIP induction.
维生素C（Vit C）与铁代谢与代谢紊乱密切相关。然而，铁储存蛋白铁调素与Vit C之间的关系尚未阐明。我们旨在研究Vit C与铁调素之间的相互作用及其对非酒精性脂肪性肝病（NAFLD）的影响。从2017 - 2018年美国国家健康与营养检查调查（NHANES）公共数据中获取了3614名受试者的临床信息。在这项横断面研究中，选择了用于评估肝脏脂肪变性和纤维化以及Vit C的FibroScan数据，以评估影响NAFLD的因素。通过受控衰减参数（CAP）和E值评估不同类别肝脏脂肪变性和纤维化中的铁调素和Vit C。使用逻辑回归和限制性立方样条（RCS）模型分析相关性。在HepG2细胞中进行研究以验证相关调控。随着肝脏脂肪变性和肝纤维化加重，铁调素升高而Vit C降低（均P < 0.001）。逻辑回归模型表明，在调整连续和分类变量后，血清铁调素升高是NAFLD的危险因素，而Vit C升高是NAFLD和肝纤维化的保护因素。Vit C与铁调素呈负相关。进一步的中介分析表明，铁调素介导了Vit C对NAFLD（P < 0.05）和肝硬化（P < 0.001）的影响。细胞水平实验表明，Vit C通过抑制棕榈酸/油酸（PA/OA）诱导的铁结合蛋白铁调素上调和不稳定铁池（LIP）诱导，减轻PA/OA诱导的脂肪变性并维持铁稳态。总之，Vit C是肝脂肪变性和纤维化的保护因素，而铁调素是危险因素。Vit C通过抑制铁调素和诱导LIP减轻NAFLD并维持铁稳态。
