PUFA supplementation-dependent incorporation of ω-3 and ω-6 fatty acids into phospholipids and triglycerides in the intestinal epithelium of Gpx4⁺/⁻IEC mice on a Western diet

Transgenic Gpx4+/−IEC mice exhibit diminished GPX4 activity specifically in the intestinal epithelium and develop features of small-intestinal Crohn’s-like disease when challenged with a Western diet and exposed to excess polyunsaturated fatty acids (PUFAs) [1,2]. To investigate the incorporation and distribution of PUFA species in intestinal epithelial phospholipid and neutral lipid classes, we profiled phosphatidylcholines, phosphatidylethanolamines, and triglycerides using a lipidomics approach based on ultraperformance chromatography-ESI-tandem mass spectrometry. The analysis focused on changes in the epithelial proportion of ω-3 and ω-6 PUFAs in these lipid classes. For this purpose, 8- to 10-week-old Gpx4+/−IEC mice were fed either a Western diet (ssniff, TD88137) or a PUFA-enriched Western diet (TD88137 + 10% fish oil) ad libitum for three months. Lipids were extracted from tissue homogenates of small intestinal scrapings from Gpx4⁺/⁻IEC mice fed the respective diets. Our data reveal substantial enrichment of ω-3 and ω-6 PUFAs across lipid classes upon PUFA supplementation, accompanied by rearrangements in overall lipid composition. The uploaded files contain the following parts: 1) A sample list describes the sample id, mice genotype (wt and Gpx4+/−IEC), diet (WD and PUFA-WD), intestine tissue section (Duodenum, Jejunum or Ileum), tissue weight, volume of PBS for homogenate preparation as well as the homogenate concentration. 2) A batch list describes the lipid species (phosphatidylcholine (PC), phosphatidylethanolamine (PE) and triglycerides (TG)), batch number, sample number as well as the corresponding Analyst wiff file name. 3) A zip file including the individual raw data files of PC, PE and TG after the lipidomics measurement. The data has been shown in the following original article: Meyer et al., Metabolic stress sensing by epithelial RXRα links Westernization of diet with Crohn’s disease. Cell Metab. 2025, 10.1016/j.cmet.2025.11.008.