Researchers find a major cause of fatty liver disease, leaky gut

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Excessive consumption of fructose — a common sweetener in the American diet — can result in non-alcoholic fatty liver disease (NAFLD), which is comparably abundant in the United States.

But a recent study found that fructose only harms the liver after it reaches the intestines, where the sugar disrupts the barrier protecting internal organs from bacterial toxins in the gut.

The researchers suggest that treatments that prevent intestinal barrier disruption could protect the liver from NAFLD, a condition that affects one in three Americans.

The study is from the University of California San Diego. The findings are published in Nature Metabolism. One author is Michael Karin, Ph.D.

NAFLD is the most common cause of chronic liver disease in the world. It can progress to more serious conditions, such as cirrhosis, liver cancer, liver failure, and death.

Fructose consumption in the U.S. has skyrocketed since the 1970s, and high fructose corn syrup (HFCS), a cheaper sugar substitute, is broadly used in processed and packaged foods, from cereals and baked goods to soft drinks.

Multiple studies have linked increased HFCS consumption with the nation’s obesity epidemic and many inflammatory conditions, such as diabetes, heart disease, and cancer.

The U.S. Food and Drug Administration, however, currently regulates it similar to other sweeteners, such as sucrose or honey and advises only moderation of intake.

The study defines a specific role and risk for HFCS in the development of fatty liver disease.

Fructose is broken down in the human digestive tract by an enzyme called fructokinase, which is produced both by the liver and the gut.

Using mouse models, the researchers found that excessive fructose metabolism in intestinal cells reduces the production of proteins that maintain the gut barrier — a layer of tightly packed epithelial cells covered with mucus that prevent bacteria and microbial products, such as endotoxins, from leaking out of the intestines and into the blood.

Thus, by deteriorating the barrier and increasing its permeability, excessive fructose consumption can result in a chronic inflammatory condition called endotoxemia, which has been documented in pediatric NAFLD patients.

The team found that leaked endotoxins reaching the liver provoked increased production of inflammatory cytokines and stimulated the conversion of fructose and glucose into fatty acid deposits.

They said it is very clear that fructose does its dirty work in the intestine, and if intestinal barrier deterioration is prevented, the fructose does little harm to the liver.

The scientists noted that feeding mice with high amounts of fructose and fat results in particularly harmful health effects.

That’s a condition that mimics the 95th percentile of relative fructose intake by American adolescents, who get up to 21.5% of their daily calories from fructose, often in combination with calorie-dense foods like hamburgers and French fries.

Interestingly, the team also found that when fructose intake was reduced below a certain threshold, no adverse effects were observed, suggesting only excessive and long-term fructose consumption represents a health risk.

Moderate fructose intake through normal consumption of fruits is well-tolerated.

If you care about liver health, please read studies about the key to stopping the silent killer of liver disease and findings of this common painkiller drug may affect your liver.

For more information about liver disease, please see recent studies about people with this health problem have higher risk of liver cancer and results showing which drug are most toxic to the liver?

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