Scientists found that blocking a sugar-processing enzyme reduces alcohol use and liver damage.
Recent work from scientists at the University of Colorado Anschutz has revealed a surprising relationship between the body’s sugar processes and the way alcohol addiction develops. The findings, described in a paper in Nature Metabolism, suggest that alcohol triggers an internal chain reaction that leads the body to make its own fructose, the same sweetener found in many foods. This reaction depends on an enzyme known as ketohexokinase, or KHK. According to the researchers, this enzyme plays a major role in two problems: the desire to drink more and the gradual damage that alcohol causes to the liver.
The team uncovered this connection while studying how alcohol alters normal metabolic patterns. They learned that alcohol activates a pathway that converts glucose into fructose inside the body. Once that happens, KHK goes to work. The enzyme breaks down fructose in a way that appears to encourage repeated drinking while also worsening stress on the liver. This dual effect caught the attention of the researchers, who wondered if blocking KHK might reduce both alcohol use and liver injury.
They tested this idea in a series of mouse studies. Mice that lacked KHK from birth drank far less than typical mice when given the choice. They behaved differently in tests that measure reward seeking and showed less activation in parts of the brain linked to habit formation and cravings. The shift in behavior suggested that without KHK, the drive to drink simply did not take hold in the same way.
The researchers noticed something else as well. Mice without KHK did not develop the usual liver problems seen in animals given steady access to alcohol. Their livers showed far less fat buildup, less swelling, and fewer early signs of scarring. Even when medication was used instead of genetics to disrupt the enzyme, the protection remained. That result supported the idea that lowering fructose production may slow or block the chain of events that leads to liver disease in heavy drinkers.
The senior researchers explained that alcohol does not work alone when causing harm. They described it as a substance that alters the body’s sugar activity in a way that feeds into addiction and injury at the same time. They believe that reducing fructose production may break the loop that keeps people drinking while their livers decline. Because another widespread condition, known as metabolic dysfunction-associated steatotic liver disease, also depends on similar fructose-related processes, the same method may one day help people with liver damage linked to diet.
The research team sees this discovery as an opening toward new treatment approaches for both alcohol addiction and liver disease. Instead of focusing only on alcohol itself, future therapies might target the sugar pathway that becomes overactive when alcohol is repeatedly consumed. The work is still early, but it offers a direction that could bring fresh options for conditions that have long been difficult to treat.
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Blocking one enzyme may break the link between alcohol and liver disease
Blocking One Enzyme May Curb Alcohol Addiction and Protect the Liver
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