Transient high fat diet causes persistent susceptibility to ferroptosis in CD8 T cells [Ex_vivo_RNAseq]

Whether past history of a high fat diet (HFD) leads to immune dysfunction is less understood. Moreover, whether factors other than persistent epigenetic changes would impact on the immune function remain unknown.

We find that even a transient exposure to HFD causes persistent metabolome changes and long-term vulnerability of CD8 T cells to oxidative stress. The past HFD signature of CD8 T cells includes enrichment of lipid species highly susceptible to ferroptosis, and depletion of metabolites with anti-oxidant function. We find that xanthine, through the salvage purine pathway fuels the GTP, which is subsequently converted to tetrahydrobiopterin (BH4) and dihydrobiopterin (BH2).