脂肪酸特异性脂质重塑对炎症反应及肠道上皮屏障功能的影响

Abstract

Effects of fatty acid with different degree of unsaturation on intestinal epithelial barrier functions were investigated. • Double-bond number shaped distinct lipid remodeling patterns among OA, LA, and ALA. • LA-induced barrier injury was associated with Cer/SM imbalance and maladaptive phospholipid remodeling. • ALA preserved LPC/PC and PC/PE balance while enriching membrane phospholipids and attenuating oxidative inflammation. Intestinal epithelial cells are the primary site for the absorption of dietary unsaturated fatty acids, yet the distinct effects of these fatty acids on epithelial barrier integrity and lipid homeostasis remain unclear. Here, we compared the effects of oleic acid (OA), linoleic acid (LA), and α -linolenic acid (ALA), respectively, in differentiated Caco-2 monolayers. LA markedly impaired epithelial barrier integrity, as indicated by disrupted tight junction organization, enhanced oxidative stress, and activation of TLR4/MyD88/NF- κ B inflammatory signaling. By contrast, OA induced relatively mild alterations, whereas ALA better preserved epithelial homeostasis, accompanied by enhanced antioxidant defense and attenuated inflammatory signaling. Untargeted lipidomics revealed fatty acid-specific remodeling of cellular lipid homeostasis. LA promoted free fatty acid accumulation, sphingolipid/phospholipid imbalance, and cardiolipin remodeling, suggesting a lipid-disruptive profile associated with barrier dysfunction. Conversely, ALA enriched structural phospholipids, including PC, PE, PI, and PS, while limiting free fatty acid accumulation, indicating a membrane lipid profile favorable for epithelial stability and lipid homeostasis. Download: Download high-res image (136KB) Download: Download full-size image