Transcriptome data of Huh7 cells treated with glucose or fructose

At the nutrient level, fructose treatment alone did not induce severe endoplasmic reticulum (ER) stress compared to glucose. However, upon KHK-C overexpression, fructose treatment led to significant ER stress.

At the genetic level, glucose treatment did not trigger ER stress even with KHK-C overexpression, whereas fructose treatment under the same conditions resulted in pronounced ER stress. Additionally, Aldob knockdown further exacerbated ER stress. In summary, our findings suggest that in Huh7 cells, KHK-C-mediated phosphorylation of fructose into fructose-1-phosphate (F1P) leads to intracellular F1P accumulation, which drives severe ER stress.