Choline Deficiency Drives the Inflammation–Fibrosis Cascade: A Spatiotemporal Atlas of Hepatic Injury from Weeks 6 to 10

作者：Shang Li, Guoqiang Zhang, Rou Li, Rou Li, Xu Zhao, Axi Shi, Qingmin Dong, Changpeng Chai, Xiaojing Song, Yuhui Wei, Xun Li, Xun Li · 发表于：Antioxidants · 年份：2026 · DOI：10.3390/antiox15010110 · 被引用次数：2 · 研究领域：Liver Disease Diagnosis and Treatment、Liver Disease and Transplantation、Folate and B Vitamins Research

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory roles throughout MASLD progression remain insufficiently defined. A 10-week high-fat, choline-deficient (HFCD) mouse model was established, and liver pathology was evaluated at weeks 6, 8, and 10. Time-resolved assessments combined untargeted metabolomics, magnetic resonance imaging-proton density fat fraction (MRI-PDFF), serum biochemistry, histological staining, immunofluorescence, and transmission electron microscopy to characterize dynamic alterations in lipid metabolism, redox status, inflammation, and fibrogenesis. The HFCD diet produced a clear temporal sequence of liver injury. Steatosis, phosphatidylcholine depletion, and early antioxidant loss appeared by week 6. By week 8, mitochondrial structural damage and pronounced cytokine elevation were evident. At week 10, collagen deposition and α-SMA activation signaled fibrotic progression. Metabolomics indicated significant disruptions in pathways related to ATP-binding cassette (ABC) transporters, one-carbon metabolism, and the tricarboxylic acid (TCA) cycle. Using integrated analytical strategies, this study suggests that choline deficiency may be associated with...