High-fructose consumption induces endoplasmic reticulum stress in visceral adipose tissue of male C57BL/6 mice, and this stress response is absent in mice lacking ketohexokinase, demonstrating that ketohexokinase-dependent fructose metabolism triggers cellular stress pathways in adipose tissue.

When fructose enters fat cells in the abdomen, an enzyme called ketohexokinase breaks it down, which uses up a lot of energy in the cell and creates harmful byproducts. This energy loss and these byproducts damage the cell's internal protein factory, causing it to malfunction and trigger a stress response. Without this enzyme, fructose does not cause this damage, even if it is present in large amounts.