December 3, 2023

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The mechanism of fructose gaining weight has been found!

The mechanism of fructose gaining weight has been found!


The mechanism of fructose gaining weight has been found!

Nature is heavy! Fructose increases intestinal villi by 40% and promotes nutrient absorption. 

Fructose is a sweetener naturally found in fruit and honey, and a component of high fructose corn syrup, which is used to sweeten foods and beverages.

Fructose is found in fruit drinks, milk tea, baked goods, and sweetened yogurt.


More and more milk tea shops are opened, and the drinks are getting better and better.

We are consuming more fructose than at any time in history, but the cost of increased fructose consumption has been increased rates of obesity and cancer.


Fructose metabolism begins in the small intestinal epithelium, where fructose is transported by the type 5 glucose transporter ( GLUT5; encoded by SLC2A5) and phosphorylated by ketohexanol to form fructose 1-phosphate, which can accumulate to high intracellular levels. level.

Although this pathway has been implicated in obesity and tumor promotion, the exact mechanism remains unclear.


A recent study published in the journal Nature found that consuming fructose increases the survival rate of intestinal epithelial cells, thereby increasing the length of the intestinal villi, allowing them to absorb more nutrients .

Studies have shown that the main metabolite of fructose promotes villi elongation.

The villi of mice fed the fructose-containing diet were 25% to 40% longer than those of mice not fed fructose, which led to the mice gaining weight.


The mechanism of fructose gaining weight has been found!DOI: 10.1038/s41586-021-03827-2


The mechanism of fructose gaining weight has been found!


Villuss are elongated, hair-like structures that line the interior of the small intestine.

The villi expand the surface area of ​​the gut and help the body absorb nutrients, including fats, from food as it passes through the digestive tract.

Thus, increased villus length is associated with increased nutrient absorption, weight gain, and fat accumulation in animals.

Interestingly, fructose’s increased villi was discovered by accident. Initially, the research team did not intend to study the small intestinal villi.


Previous research by the team, published in 2019, found that dietary fructose increased tumor size in a mouse model of colorectal cancer, and blocking fructose metabolism prevented this from happening.

Considering that fructose may also promote hyperplasia or accelerated growth of the small intestine, the researchers examined the tissue structure of mice treated with fructose or a control diet under a microscope.


The study observed a significant increase in villus length in mice fed a high fructose diet. When the researchers discovered this unexpected result, the research team immediately began to study the villi, to determine whether these villi function differently when they increased in length.


Therefore, they divided the mice into 3 groups: a control diet without fructose, a standard high-fat diet with glucose without fructose (45% of calories from fat), and an isocaloric high-fat diet (with glucose replaced by sucrose, sucrose). half glucose, half fructose).


The study found that despite consuming the same amount of energy in each group, mice fed fructose in the form of sucrose had significantly higher body weight and fat mass and longer small intestinal villi than mice on a high-fat diet without fructose.


The mechanism of fructose gaining weight has been found!Mice fed fructose weighed more and had longer villi


In addition, mice fed fructose in the form of sucrose had higher levels of serum triglycerides after oral fat compared to control mice without sucrose.


These data suggest that dietary fructose increases gut villi length and nutrient absorption.


Next, the researchers took a closer look at the metabolic changes in the fructose group of mice and found that a specific metabolite of fructose, called fructose-1-phosphate, was accumulating at high levels in the cells.

In hypoxic intestinal cells, fructose-1-phosphate increases the survival of intestinal epithelial cells by inhibiting the M2 isoform of pyruvate kinase (PK), thereby increasing the length of intestinal villi .

In addition, previous animal studies have shown that this fructose metabolite also contributes to tumors.


The mechanism of fructose gaining weight has been found!Fructose metabolism enhances hypoxic cell viability and reduces pyruvate kinase activity


The research team then activated pyruvate kinase via TEPP-46, which prevented the increase in intestinal villus length and abrogated the weight gain and tumor growth caused by high-fructose-fed mice.


Activation of PK attenuates the effect of fructose on hypoxia survival


From an evolutionary standpoint, it makes sense that high fructose intake increases fat synthesis, said study author Taylor’s. “In mammals, especially mammals that hibernate in temperate climates, fructose is very readily available during the autumn months when fruit ripens. Eating large amounts of fructose may help these animals absorb more nutrients and convert them into fat , so that they can spend the winter safely.


Dr Goncalves added that humans have not evolved to eat what we now eat every day. Before, fructose was not freely available all year round, but only in limited seasons.

But nowadays, fructose is almost everywhere, whether it comes from milk tea , beverages, cookies, or from natural foods like fruits, we can get and enjoy them anytime.


“While fructose itself is not harmful, eating too much fructose can be harmful. Our bodies are not designed to eat that much fructose,” he said.


“This research discovery has an opportunity to translate to humans. There are already clinical trials of drugs for other purposes that target the enzymes responsible for the production of fructose-1-phosphate,” Dr. Goncalves said. “We wanted to find a way to use They shorten the villi, thereby reducing fat absorption and possibly slowing tumor growth.”

Not only for a healthy body, but also to reduce the risk of cancer, don’t over-consume fructose.



The mechanism of fructose gaining weight has been found!

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