Scientists from the University of Colorado Anschutz have discovered a surprising link between the body's sugar metabolism and alcohol addiction, opening new possibilities for treating both alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). Their study, published in Nature Metabolism, reveals that alcohol consumption stimulates an internal production of fructose-the same sugar common in sweet foods-through the enzyme ketohexokinase (KHK). This pathway appears to encourage further drinking and worsens liver damage.
The team conducted experiments using mice genetically engineered to lack KHK, observing that these mice showed significantly reduced alcohol preference and consumption. Tests included voluntary drinking and reward-based models. Additionally, blocking KHK, either genetically or with medication, prevented liver injury typically caused by alcohol. This included reductions in liver fat buildup, inflammation, and scarring.
"This shows alcohol doesn't just harm the liver directly, it hijacks our sugar metabolism to reinforce drinking and accelerate liver injury," said lead researcher Dr. Miguel Lanaspa. The findings suggest that targeting fructose metabolism could break this harmful cycle.
Moreover, since both ALD and metabolic-associated steatotic liver disease (MASLD) involve fructose-driven damage, therapies inhibiting fructose metabolism may benefit a broad group of patients suffering from liver disease related to diet or alcohol.
Co-author Dr. Richard Johnson emphasized this unexpected intersection between sugar and alcohol metabolism, highlighting its potential to spur new treatments addressing the root metabolic pathways common to these liver illnesses.
This discovery offers hope in tackling two pressing health challenges — alcohol addiction and liver disease — with innovative strategies focused on controlling fructose production and activity in the body.
REFERENCE: Andres-Hernando, A., et al. (2025). Identification of a common ketohexokinase-dependent link driving alcohol intake and alcohol-associated liver disease in mice. Nature Metabolism. doi: 10.1038/s42255-025-01402-x. https://www.nature.com/articles/s42255-025-01402-x
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