mpared to their peers on the glucose diet.
And while both groups of animals added fat to their livers, the fat composition was quite different.
The researchers also discovered that production of an enzyme called Khk (ketohexokinase), required for the first step of fructose metabolism, was increased in the livers of mice who drank fructose.
When the scientists examined liver samples from obese human teenagers with fatty liver disease, they also found higher levels of Khk.
The Khk enzyme is specifically important in fructose, but not glucose, metabolism. (“Although fructose and glucose are both sugars, cells handle them very differently,” says Kahn.) That meant, the scientists saw, that it might offer a target to clamp down on fructose metabolism.
The treatment lowered liver weight and improved glucose tolerance among mice on any diet, but most strikingly among those on the high-fat/high-fructose diet.
Looking ahead, the researchers will continue to explore the Khk biological pathway and to look for other promising molecular targets for treating fatty liver disease.
“This disease is almost always associated with obesity,” notes Kahn. “Once your fat cells get really full of fat and they can’t hold any more, fat winds up going in other tissues, and the liver is the next best place.”
Almost all obese people with diabetes add some fat to their livers.
“These people are more at risk of developing fatty liver disease, just as those with fatty liver disease are more at risk of developing diabetes, since obesity is being a predisposing factor for both conditions,” says Softic.
As obesity spreads worldwide, so will the burden of fatty liver disease and associated liver failure, which is predicted to become the most common factor driving the need for liver transplants, he says.
The disease afflicts people of every age, but has become a particular problem in children, now that about one-fifth of U.S. school-age children are obese, according to the Centers for Disease Control and Prevention.
“The disease is much more worrisome in a child of thirteen who goes from normal liver to fatty liver to liver inflammation over the span of several years than in somebody who’s been overweight for 30 years,” says Softic.
“Kids also eat more sugar than adults, so fructose may be even more of a risk factor in children, which would add to their years of poor health.”