Genetic deletion of ketohexokinase in male C57BL/6 mice prevents fructose-induced visceral obesity when dietary fructose intake is held constant, demonstrating that ketohexokinase-dependent metabolism is necessary for fructose to promote fat accumulation in abdominal adipose depots.

When fructose enters fat cells in the belly, an enzyme called ketohexokinase breaks it down, which drains energy from the cells and creates harmful byproducts. This triggers stress and inflammation inside the fat cells, which stops them from releasing a key hormone that keeps fat burning and insulin levels normal. Without this hormone, fat stops being burned and starts storing instead, causing the belly to grow larger.