Iron deficiency aggravates hepatic inflammation in suckling piglets via endoplasmic reticulum stress-driven NF-κB pathway activation

作者：Jun Qi, Yaxu Liang, Dongming Yu, Weite Li, Fei Long, Meng Yuan, Zhangbo Lou, Chunxue Liu, Gaiqin Wang, Baojun Wu, Xiang Zhong · 发表于：Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · 年份：2026 · DOI：10.1186/s40104-026-01356-4 · 被引用次数：1 · 研究领域：Iron Metabolism and Disorders、Endoplasmic Reticulum Stress and Disease、Plant Micronutrient Interactions and Effects

BACKGROUND: Iron deficiency (ID) poses a significant health burden to both human infants and suckling piglets. In piglets, ID leads to substantial economic losses for the industry by compromising growth performance, health, and survival. However, current research has predominantly concentrated on hematological abnormalities, whereas the mechanisms underlying ID-associated hepatic inflammatory injury remain inadequately elucidated. Our study employed the iron-deficient suckling piglet model to address this knowledge gap and to establish a molecular theoretical foundation. RESULTS: To investigate the underlying mechanisms, this study conducted in vivo and in vitro models. In piglets, ID triggered hepatic oxidative stress by inducing a redox imbalance and suppressing the core Nrf2/HO-1 antioxidant signaling pathway. Histopathological examination revealed structural abnormalities in ID piglet livers, including disorganized hepatic cords, cytoplasmic vacuolation, hydropic degeneration, and mononuclear inflammatory cell infiltration. Transmission electron microscopy further showed shrunk nuclear envelopes, reduced numbers of rough endoplasmic reticulum (RER), and dilated RER cisternae in hepatocytes of ID piglets. Mechanistically, ID activated endoplasmic reticulum stress (ERS) and the PERK/IRE1α branches of the unfolded protein response (UPR). RNA-seq transcriptomic analysis demonstrated significant dysregulation of immune-related pathways, accompanied by elevated pro-inflammatory...