One enzyme could be behind alcohol addiction and liver disease

Scientists have uncovered a surprising connection between sugar metabolism and alcohol addiction, identifying a potential new therapeutic target for treating alcohol-associated liver disease (ALD) and alcohol use disorder (AUD).

In a study appearing in Nature Metabolism, University of Colorado Anschutz researchers found that alcohol triggers a metabolic pathway in the body that leads to the internal production of fructose, the same type of sugar commonly found in sweetened foods and beverages.

This process, driven by the enzyme ketohexokinase (KHK), appears to play a key role in both reinforcing alcohol consumption habits and accelerating liver damage.

Researchers discovered that mice lacking KHK showed markedly lower alcohol inclination and consumption. These mice drank less alcohol across multiple tests, including voluntary drinking and reward-based models, and exhibited reduced activity in brain regions associated with addiction.

Importantly, alcohol-induced liver injury appeared to be nonexistent when KHK was blocked, either genetically or through medication. Livers displayed reduced fat accumulation, inflammation and scarring, suggesting that interfering with fructose metabolism could halt or even prevent alcohol-related liver disease progression.

"Our findings show that alcohol doesn't just damage the liver directly, it hijacks the body's sugar metabolism in a way that enhances drinking behavior and worsens liver injury," said Miguel A. Lanaspa, DVM, Ph.D., associate research professor at CU Anschutz and senior author.

"By targeting fructose metabolism, we may be able to break this cycle and develop new treatments for both alcohol addiction and liver disease."

Because both alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease (MASLD) share fructose-driven mechanisms, the results suggest that therapies designed to inhibit fructose metabolism could benefit a broad range of patients with liver disease linked to diet or alcohol use.

"This discovery highlights an unexpected intersection between sugar and alcohol metabolism," said Richard Johnson, MD, professor at CU Anschutz and study co-author. "It opens exciting possibilities for developing treatments that target a common pathway underlying both metabolic and alcohol-related liver diseases."

The research provides a promising new direction for addressing liver disease and alcohol addiction, conditions for which effective treatments remain limited.

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