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Model; VPA induces the UPR pathway by increasing intracellular ceramide levels. In the proposed model, VPA-mediated inositol depletion leads to increased expression of fatty acid elongases, specifically FEN1 and SUR4, which catalyze the synthesis of C24 and C26 fatty acids and ceramides, especially PHC containing C24–C26 fatty acids. Increased ceramide levels decrease expression of nutrient transporters, stressing the cell due to lack of nutrients and inducing the UPR pathway.
