Researchers discover how fructose enhances fat absorption in the gut

A new preclinical study published in the journal Nature is demonstrating how fructose can alter cells in the small intestine, subsequently enhancing nutrient absorption and promoting weight gain. The research indicates excessive fructose consumption, such as drinks sweetened with high-fructose corn syrup (HFCS), increases the body’s ability to absorb dietary fats.

The new research stemmed from a 2019 study investigating the effect of HFCS on colorectal cancer. That study discovered a molecular mechanism by which fructose directly enhances tumor cell growth. So the next logical study target was the effect fructose had on non-cancerous intestinal cells.

Lining our small intestine are millions of tiny, hairlike protrusions known as villi, which serve a number of functions, including absorbing nutrients from food.

The first finding in the new research was that mice fed high-fructose diets were found to have villi up to 40 percent longer than animals not fed fructose. Subsequent investigation revealed mice with these longer villi gained more weight on a high-fat diet than mice fed a high-fat diet without added fructose.

Drilling down into the molecular mechanism at work, the researchers detected high levels of fructose-1-phosphate accumulating in cells. Fructose-1-phosphate is a metabolite of fructose and it can boost the survival of villus cells. It is this mechanism, the researchers suggest, that is responsible for fructose promoting villi length, leading to increased fat absorption and weight gain.

Samuel Taylor, first author on the new study, hypothesizes an evolutionary reason for animals developing this unusual mechanism, saying it makes sense for mammals to maximize fat absorption from fructose in overripe fruit.

“In mammals, especially hibernating mammals in temperate climates, you have fructose being very available in the fall months when the fruit is ripe,” says Taylor. “Eating a lot of fructose may help these animals to absorb and convert more nutrients to fat, which they need to get through the winter.”

But the problem that arises in modern times is one of overconsumption of fructose in forms of sweeteners such as high-fructose corn syrup. As senior author Marcus DeSilva Goncalves explains, the issue is simple, we now eat too much fructose.

“Fructose itself is not harmful,” notes Goncalves. “It's a problem of overconsumption. Our bodies were not designed to eat as much of it as we do.”

This is not the first study to shine a light on the potential damage caused by excessive fructose consumption. An influential 2019 study looked at the influence of fructose on the liver and found it exerted novel metabolic effects on the organ, resulting in greater accumulations of fat. This effect was not seen with glucose.

More work needs to be done to confirm the findings of this new study in humans, but Goncalves says if these findings are validated in humans they could potentially lead to new methods for treating colorectal cancers and obesity.

“There are already drugs in clinical trials for other purposes that target the enzyme responsible for producing fructose-1-phosphate,” says Goncalves. "We're hoping to find a way to repurpose them to shrink the villi, reduce fat absorption, and possibly slow tumor growth.”

The new research was published in the journal Nature.

Source: Weill Cornell Medicine