Too much sorbitol may raise fatty liver disease risk, study finds
Zebrafish study finds sugar substitute converts to fructose in liver
Excessive intake of sorbitol, a type of sugar naturally found in many fruits and used as a sugar substitute, may increase the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), a type of fatty liver disease, according to a study in zebrafish.
While certain bacteria in the zebrafish gut were found to break down sorbitol and protect against MASLD, these could become overwhelmed in the presence of excessive amounts of sorbitol, the data showed.
Sorbitol “can be produced in the body at significant levels,” Gary Patti, PhD, the study’s senior author and a chemistry professor at Washington University in St. Louis, said in a university news story. “But if you have the right bacteria, turns out, it doesn’t matter.”
“If you don’t have the right bacteria, that’s when it becomes problematic,” Patti said. “Because in those conditions, sorbitol doesn’t get degraded and as a result, it is passed on to the liver.” There, it is transformed into the simple sugar molecule fructose, which has been shown to promote fatty liver disease.
The study, “Intestine-derived sorbitol drives steatotic liver disease in the absence of gut bacteria,” was published in Science Signaling.
Gut microbiome is key to protecting liver
MASLD is characterized by excessive fat in the liver that typically occurs in association with cardiometabolic risk factors, including high blood pressure, being overweight or obese, and high blood sugar (glucose) levels.
Dietary factors are believed to play a key role in MALSD development. Excess calorie intake has been associated with liver fat accumulation, and certain carbohydrates, including the sugar molecule fructose, have been linked to an increased risk.
Crosstalk between the body’s own cells and the microbes living in the intestines (gut microbiome) has been shown to help regulate liver fat buildup. Changes in the gut microbiome have also been tied to MASLD development and progression.
Patti’s team used a zebrafish model, which has emerged as a valuable tool for MASLD research. While zebrafish are not directly comparable to humans, their glucose/fat metabolism and liver physiology are similar to those of mammals.
The team depleted the gut microbiome in adult zebrafish using antibiotics, resulting in a buildup of fat in the liver even when the animals were maintained on standard diets.
The researchers then applied metabolomics and isotope tracing: Metabolomics is the study of the abundance and types of metabolites, small molecules produced by metabolism. Isotope tracing is a technique in which molecules are labeled with a non-radioactive molecule and can be tracked throughout the body after consumption.
Results showed that when found at high levels in the intestines, dietary glucose — one of the byproducts of carbohydrate breakdown — can be converted into sorbitol, a type of sugar naturally found in fruits like apples and pears and used as a sweetener in sugar-free gum, candy, and diet foods.
While sorbitol was degraded by gut bacteria in healthy zebrafish, it was transferred to the liver in animals without gut microbiome. Once in the liver, sorbitol was converted to a sugar called fructose-1-phosphate.
This sugar molecule activated glucokinase, an enzyme that promotes glucose breakdown for energy and ultimately increases fat production in the liver.
When the team blocked sorbitol production in microbiome-depleted zebrafish, the onset of fatty liver disease was prevented. At the same time, recolonizing these fish with a type of bacteria that degrades sorbitol, called Aeromonas, reversed fatty liver disease.
Nevertheless, providing the fish with a high level of dietary sorbitol mimicked the effects of gut microbiome depletion, resulting in the development of fatty liver disease.
“These findings show that sorbitol-degrading bacteria in the gut protect against steatotic liver disease and suggest that excessive intake of dietary sorbitol may pose a risk for the development of MASLD,” the researchers wrote.
About the Author
