08.20.21
Eating fructose appears to alter cells in the digestive tract in a way that enables it to take in more nutrients, according to a preclinical study from investigators at Weill Cornell Medicine and New York-Presbyterian. Results were published in Nature.
These changes could help to explain the link between rising fructose consumption around the world and increased rates of obesity and certain cancers, researchers said.
The study focused on the effect of a high-fructose diet on villi, the thin, hair-like structures that line the inside of the small intestine. Villi expand the surface area of the gut and help the body to absorb nutrients, including dietary fats, from food as it passes through the digestive tract. The study found that mice fed diets that included fructose had villi that were 25-40% longer than those of mice that were not fed fructose. Additionally, the increase in villus length was associated with increased nutrient absorption, weight gain and fat accumulation in the animals.
“Fructose is structurally different from other sugars like glucose, and it gets metabolized differently,” said senior author Dr. Marcus DaSilva Goncalves, an endocrinologist at New York-Presbyterian/Weill Cornell Medical Center. “Our research has found that fructose’s primary metabolite promotes the elongation of villi and supports intestinal tumor growth.”
Researchers put mice into three groups: a normal low-fat diet, a high-fat diet, and a high-fat diet with added fructose. Not only did the mice in the third group develop longer villi, but they became more obese than the mice receiving the high-fat diet without fructose.
The researchers took a closer look at the changes in metabolism and found that a specific metabolite of fructose, called fructose-1-phosphate, was accumulating at high levels. This metabolite interacted with a glucose-metabolizing enzyme called pyruvate kinase, to alter cell metabolism and promote villus survival and elongation. When pyruvate kinase or the enzyme that makes fructose-1-phospate were removed, fructose had no effect on villus length. Previous animal studies have suggested that this metabolite of fructose also aids in tumor growth.
The observations in mice make sense from an evolutionary perspective, according to lead author Samuel Taylor, a Tri-Institutional MD-PhD program student in Goncalves’ lab. “In mammals, especially hibernating mammals in temperate climates, you have fructose being very available in the fall months when the fruit is ripe,” he said. “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.”
Goncalves added that humans did not evolve to eat what they eat now. “Fructose is nearly ubiquitous in modern diets, whether it comes from high-fructose corn syrup, table sugar, or from natural foods like fruit,” he said. “Fructose itself is not harmful. It's a problem of overconsumption. Our bodies were not designed to eat as much of it as we do.”
Future research will aim to confirm that the findings in mice translate to humans.
These changes could help to explain the link between rising fructose consumption around the world and increased rates of obesity and certain cancers, researchers said.
The study focused on the effect of a high-fructose diet on villi, the thin, hair-like structures that line the inside of the small intestine. Villi expand the surface area of the gut and help the body to absorb nutrients, including dietary fats, from food as it passes through the digestive tract. The study found that mice fed diets that included fructose had villi that were 25-40% longer than those of mice that were not fed fructose. Additionally, the increase in villus length was associated with increased nutrient absorption, weight gain and fat accumulation in the animals.
“Fructose is structurally different from other sugars like glucose, and it gets metabolized differently,” said senior author Dr. Marcus DaSilva Goncalves, an endocrinologist at New York-Presbyterian/Weill Cornell Medical Center. “Our research has found that fructose’s primary metabolite promotes the elongation of villi and supports intestinal tumor growth.”
Researchers put mice into three groups: a normal low-fat diet, a high-fat diet, and a high-fat diet with added fructose. Not only did the mice in the third group develop longer villi, but they became more obese than the mice receiving the high-fat diet without fructose.
The researchers took a closer look at the changes in metabolism and found that a specific metabolite of fructose, called fructose-1-phosphate, was accumulating at high levels. This metabolite interacted with a glucose-metabolizing enzyme called pyruvate kinase, to alter cell metabolism and promote villus survival and elongation. When pyruvate kinase or the enzyme that makes fructose-1-phospate were removed, fructose had no effect on villus length. Previous animal studies have suggested that this metabolite of fructose also aids in tumor growth.
The observations in mice make sense from an evolutionary perspective, according to lead author Samuel Taylor, a Tri-Institutional MD-PhD program student in Goncalves’ lab. “In mammals, especially hibernating mammals in temperate climates, you have fructose being very available in the fall months when the fruit is ripe,” he said. “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.”
Goncalves added that humans did not evolve to eat what they eat now. “Fructose is nearly ubiquitous in modern diets, whether it comes from high-fructose corn syrup, table sugar, or from natural foods like fruit,” he said. “Fructose itself is not harmful. It's a problem of overconsumption. Our bodies were not designed to eat as much of it as we do.”
Future research will aim to confirm that the findings in mice translate to humans.
