Fig. 5

Model of metabolic processes leading to accumulation of reactive oxygen species (ROS) and inflammation in TEDDY IA patients. Low expression of chylomicron membrane components is correlated with secondary metabolites (adipate) and markers of impaired β-oxidation and is consistent with lower vitamin levels and lower expression of the transcriptional regulator PPARα. Low PPARα levels may downregulate glycogen synthesis and upregulate glycolysis. Increased glycolytic flux is liked to activation of the TCA cycle, increased oxidative phosphorylation, and finally, to the production of ROS. ROS accumulation leads to increased expression of ROS-scavenging enzymes and activation of prostaglandins (PLA2) and lipoxygenases (ALOX) leading to inflammation. Continuous lines: association in KEGG; dashed lines: literature-based association; dotted lines: transcriptional regulation; double lines: partial correlations analysis-based association; blunt ends: negative relationship; arrowheads: positive relationship; red-background stars: VIP-selected variable; blue-background stars: GSEA selected variable; green borders: metabolites; blue borders: genes; orange borders: dietary biomarkers. Heatmap description: from left to right from time points 12 to 9 (2 boxes) or from 12 to 0 (5 boxes) months before seroconversion; blue: downregulation, red: upregulation in cases