Feeding mice high-fructose corn syrup, a widely used sweetener in human diets, has been found to drive an increase in the surface area of the gut that is associated with enhanced absorption of dietary nutrients and weight gain.
The incidence of obesity has been steadily increasing, tripling globally between 1975 and 2016, at a high cost to public health1. Obesity predisposes individuals to various diseases, including cancer, and the number of obesity-associated deaths globally each year (estimated at 2.8 million) is similar in scale to the reported COVID-19-associated deaths in the ongoing pandemic. Although fat-rich diets have taken much of the blame for the rise in obesity, excess consumption of processed sugars, and high-fructose corn syrup (HFCS) in particular, is strongly implicated in diet-induced obesity. Whether and how fructose causes obesity in humans remains a hotly debated question.
Moderate amounts of fructose for example, those ingested when consuming fruits are taken up and broken down by intestinal cells. Excess amounts, such as those that might be ingested after drinking a sugary beverage, overwhelm the intestine’s absorptive capacity and the fructose either ‘leaks’ into the bloodstream to reach the liver intact, or it spills over from the small intestine and reaches the colon.
Excess fructose in the liver fuels high ketohexokinase (KHK) activity, which is thought to stimulate the expression of lipid-synthesis genes by diverse mechanisms9. The depletion of KHK in the liver of mice is enough to prevent fructose-induced liver steatosis.
Fructose that ends up in the colon is broken down by resident bacteria to produce molecules that can then fuel lipid synthesis in the liver7. Furthermore, fructose increases intestinal ‘leakiness’, a condition in which loose connections between gut cells enable ingested nutrients, and toxins from bacteria in the colon, to escape to the liver, where they activate inflammatory signals from immune cells that boost steatosis.
Studies have shown that HFCS promotes metabolic pathways that support the formation of colon tumours, so the authors wondered what consequences a HFCS-rich diet might have for non-cancerous intestinal cells. Taylor et al. found that HFCS-fed mice had longer intestinal protrusions, structures known as villi and absorbed more dietary nutrients compared with mice that did not receive HFCS in their diet. Furthermore, fatty diets caused an even greater weight gain in mice if such diets also contained fructose than if they did not.
Their study provides compelling evidence that the enzyme PKM2 and its ligand F1-P mediate previously unappreciated effects of fructose in both normal and cancerous intestinal tissues. The findings also raise several questions relating to our current understanding of how the intestine handles nutrients.
The question of how ingested dietary lipids cause a rise in lipids in the blood, as they seem to do in HFCS-fed mice even when lipases are inhibited, according to Taylor and colleagues, requires further investigation.
As we can see we should think twice before consuming foods and beverages containing HFCS because of how its excess causes an increase in fat production in the liver and how it also promotes the absorption of other fats consumed in our diet, causing an increased risk of developing obesity, an inflammatory condition known to be the cause of all types of medical conditions.
Source link: https://www.nature.com/articles/d41586-021-02195-1