Fructose Contributes to Obesity

Fructose, present in modern diets, like corn syrup, table sugar, is not harmful. However, higher consumption can harm our bodies.

Consuming foods that are high in fructose can alter cells in the digestive, which in turn increases absorption of more nutrients, reveals a preclinical study from investigators at Weill Cornell Medicine and NewYork-Presbyterian.

These //changes could help to explain the well-known link between rising fructose consumption around the world and increased rates of obesity and certain cancers.

Study Claims That Fructose Itself Has No Impact on Heart Disease
Fructose is naturally found in fruit, vegetables and honey. It is the sugar often blamed for the obesity epidemic and doctors over the world warn against having an excess of fructose.

‘Fructose, present in modern diets, like corn syrup, table sugar, is not harmful. However, higher consumption can harm our bodies.’

The research, published in Nature, 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 that were fed diets that included fructose had villi that were 25 percent to 40 percent 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, the Ralph L. Nachman Research Scholar, an assistant professor of medicine in the Division of Endocrinology, Diabetes and Metabolism and an endocrinologist at NewYork-Presbyterian/Weill Cornell Medical Center. “Our research has found that fructose’s primary metabolite promotes the elongation of villi and supports intestinal tumor growth.”

Effects of Fructose Limited to Excess Calorie Intake
Fructose, the sugar often blamed for the obesity epidemic, does not have any impact on an emerging indicator for the risk of cardiovascular disease known as postprandial triglycerides, reveals a new study.

The investigators didn’t plan to study villi. Previous research from the team, published in 2019, found that dietary fructose could increase tumor size in mouse models of colorectal cancer, and that blocking fructose metabolism could prevent that from happening.

Reasoning that fructose might also promote hyperplasia, or accelerated growth, of the small intestine, the researchers examined tissues from mice treated with fructose or a control diet under the microscope.

High Fructose Consumption Causes Fatty Liver, Via Gut Manipulation
Fructose is broken down in the digestive tract by an enzyme called fructokinase, which is produced both by the liver and the gut. This excessive fructose metabolism in intestinal cells deteriorates the intestinal barrier. This harm done by fructose affescts the liver.

The observation that the mice on the high-fructose diet had increased villi length, which was made by first author Samuel Taylor, a Tri-Institutional M.D.-Ph.D. Program student in Dr. Goncalves’ lab, was a complete surprise. And once he made the discovery, he and Dr. Goncalves set out to learn more. After observing that the villi were longer, the team wanted to determine whether those villi were functioning differently. So they 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.

Fructose Does Not Impact Emerging Indicator for Cardiovascular Disease
New research has found that fructose, the sugar often blamed for the obesity epidemic, does not itself have any impact on an emerging marker for the risk of cardiovascular disease known as postprandial triglycerides.

Previous animal studies have suggested that this metabolite of fructose also aids in tumor growth.

According to Taylor, the observations in mice make sense from an evolutionary perspective. “In mammals, especially hibernating mammals in temperate climates, you have fructose being very available in the fall months when the fruit is ripe,”“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.”

Dr. 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. “There are already drugs in clinical trials for other purposes that target the enzyme responsible for producing fructose-1-phosphate,” said Dr. Goncalves, who is also a member of the Sandra and Edward Meyer Cancer Center. "We're hoping to find a way to repurpose them to shrink the villi, reduce fat absorption, and possibly slow tumor growth.”

Dr. Marcus DaSilva Goncalves is a paid consultant and shareholder of Faeth Therapeutics which is developing therapies for cancer. Dr. Goncalves has received speaking and/or consulting fees from Pfizer, Novartis, Petra Pharmaceuticals and TruMacro Nutrition. The laboratory of Dr. Goncalves has received financial support from Pfizer.

Source-Eurekalert