Graduate student University of Massachusetts Amherst Braintree, Massachusetts, United States
Disclosure(s):
Siu Wong, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Lipids, indispensable constituents of the human diet, undergo peroxidation to produce lipid peroxidation products (LPPs), which have been identified as key agents in triggering inflammation in Inflammatory Bowel Disease (IBD) patients. However, the underlying mechanisms remain elusive. This study aims to investigate the role and connection of LPPs — including 4-Hydroxyhexenal (4-HHE), an omega-3 derivative, and 4-Hydroxynonenal (4-HNE) and 4-Oxo-2-nonenal (4-ONE), which are omega-6 derivatives — in the pathogenesis of IBD.
Methods: A dextran sulfate sodium (DSS) mouse model was used to study the relationship between LPPs and IBD. Subsequently, the Raw 264.7 murine macrophage cell line was utilized to investigate the link between LPPs and inflammation. Furthermore, the human Caco-2 cell line was employed to mimic the intestinal mucosa, demonstrating the effects of LPPs on the colon.
Results: LPPs were identified as contributing factors to the development of IBD, as demonstrated by the positive correlation observed in the DSS mouse model. Studies using Raw 264.7 cells revealed that LPPs impair mitochondrial function, pointing to a novel mechanism underlying IBD. Additionally, experiments with Caco-2 cells showed that LPPs weaken and damage tight junctions, contributing to intestinal barrier dysfunction and the pathogenesis of IBD.
Conclusions: These findings elucidate the relationship between LPPs and IBD across different systems. LPPs impair mitochondrial function and damage tight junctions, thereby triggering IBD. Our study provides new insights into the mechanisms through which LPPs contribute to the development of IBD and highlights potential avenues for therapeutic development.
