IL-1β-associated inflammation, lipid metabolic alterations and epithelial barrier injury in necrotizing enterocolitis: partial protection by fenofibrate
Year: 2026
Type: article
Abstract: Introduction Necrotizing enterocolitis (NEC) is characterized by exaggerated inflammation and epithelial barrier injury, but the relationship between inflammatory signaling and intestinal lipid-metabolic dysfunction remains incompletely defined. Methods We integrated analysis of the human intestinal transcriptomic dataset GSE46619 with experiments in rat IEC-6 cells and a neonatal mouse NEC model. IEC-6 cells were challenged with LPS or recombinant IL-1β and treated with Il1b siRNA or fenofibrate. In vivo , male and female C57BL/6 neonatal mice underwent formula-feeding/hypoxia exposure from postnatal day 7 to 10 after AAV9-shIl1b or control-vector administration on postnatal day 2; a separate NEC group received fenofibrate. Results Human NEC samples showed increased inflammatory signatures and lower fatty-acid-metabolism GSVA scores, with an inverse association between IL1B expression and the fatty-acid-metabolism score. In IEC-6 cells and mouse ileum, inflammatory or NEC-like injury was accompanied by reduced tight-junction and PPARα/CPT1A-associated markers and increased lipid-peroxidation/lipid-content indices. Il1b knockdown and fenofibrate each partially attenuated these abnormalities and improved histological injury in vivo . Discussion These findings support a working model linking IL-1β-associated inflammation, lipid metabolic alterations, and epithelial barrier injury in experimental NEC. Because fatty-acid oxidation flux and PPARα loss-of-function were not tested, the data do not establish a direct IL-1β-PPARα causal pathway or strict PPARα dependency.
Source: Frontiers in Physiology
Authors: Yinghui Zhang, Yahui Zhou, Renqiang Yu, Yingzi Mei
Institution: Jiangnan University
Language: English
Topic: Infant Nutrition and Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225748896