Epoxy Triglyceride Enhances Intestinal Permeability via Caspase-1/NLRP3/GSDMD and cGAS-STING Pathways in Dextran Sulfate Sodium-Induced Colitis Mice

J Agric Food Chem. 2023 Mar 15;71(10):4371-4381. doi: 10.1021/acs.jafc.2c08134. Epub 2023 Mar 1.

Abstract

Oxidized triglyceride monomers are the main cytotoxic products of deep-frying oil. However, its impact on the intestinal barrier, the first health guardian, remains unknown. In this study, HPLC-MS/MS analysis revealed that the epoxy group is the main oxidation product, indicating that it may be the main cytotoxic factor. Therefore, 1-9,10-epoxystearic ester, 2,3-dioleic acid (EGT) and glycerol trioleate (GT) were used to reveal the effect of the epoxy group on the intestinal barrier of dextran sulfate sodium-induced colitis. Characteristics analysis showed that EGT could aggravate intestinal damage. The relative mRNA expression analysis suggested that EGT could activate Caspase-1/NLRP3/GSDMD, thereby inducing pyroptosis. The proinflammatory cytokines activated by pyroptosis and the cGAS-STING pathway were released through the pores, thus inducing the disintegration of the tight junction between the intestinal epithelial cells and enhancing intestinal permeability. Metabonomics further confirmed that EGT can change the composition and content of phospholipids on the cell membrane, indicating the morphological changes of the intestinal epithelial cell membrane. In conclusion, this study highlights that EGT induced intestinal dysfunction via Caspase-1/NLRP3/GSDMD and cGAS-STING pathways.

Keywords: epoxy; intestinal barrier; oxidized triglyceride monomer; permeability; pyroptosis.

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Colitis* / chemically induced
  • Colitis* / genetics
  • Colitis* / metabolism
  • Dextran Sulfate / metabolism
  • Disease Models, Animal
  • Intestinal Mucosa / metabolism
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Nucleotidyltransferases / metabolism
  • Permeability
  • Tandem Mass Spectrometry
  • Triglycerides / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Dextran Sulfate
  • Caspase 1
  • Triglycerides
  • Nucleotidyltransferases
  • Nlrp3 protein, mouse