Researcher Studies Negative Effects of High-Fat Diet, Fructose

It’s widely known that when it comes to diet, fast food isn’t the healthiest choice. Expanding on this knowledge, a recent study by a researcher at the University of Kentucky College of Medicine found that the inclusion of fructose-sweetened drinks with high-fat foods might add to the negative effects on one’s body.

Samir Softic, MD, assistant professor in the departments of pediatrics and pharmacology and nutritional sciences, as well as a pediatric gastroenterologist with UK HealthCare, followed up on his research from Harvard Medical School and reported that the intake of beverages sweetened by fructose, an abundant dietary monosaccharide, not only promotes the accumulation of new fat, but also reduces the burning of fat.

More specifically, when combined with a high-fat diet, fructose accelerates the development of obesity and its complications by negatively affecting the expression of genes involved in fat oxidation and modifying mitochondrial proteins related to fat metabolism. Mitochondria are primary sites of energy production and fat oxidation in a cell.

“We chose to study the interaction of sugar-sweetened drinks and high-fat diet, as meals served in fast food restaurants often combine these items on the menu,” Dr. Softic said. “Anecdotal evidence suggests that combined intake of these foods leads to worse health outcomes, but the mechanism for why this might be true was unknown. So we have been working to learn more about that.”

Fructose is a common ingredient in various foods and drinks. When combined with glucose from corn starch, it becomes high-fructose corn syrup, which is a major component of certain sodas, candy, jellies, creamers, condiments, and processed foods.

Dr. Softic’s study, published in Cell Metabolism in early October, touches on a topic particularly relevant to the Commonwealth. Diabetes and obesity are one of six Research Priorities Areas, identified by UK’s Vice President for Research. Supported by internal strategic investment funds, these six areas are marked by funding strength and scholarly activity, relevance to Kentucky and poised for growth.

A high-fat diet has been known to contribute to obesity, but Dr. Softic’s study shows that fructose might make matters worse.

His research team examined the effects of the supplementation of fructose compared to glucose, another abundant dietary monosaccharide, in mice. The team found that, although both sugars lead to fat accumulation in the liver, they are metabolized differently. Dietary fructose (but not glucose) interferes with mitochondrial size, function, and protein acetylation when paired with a high-fat diet, resulting in decreased fatty acid oxidation and metabolic dysregulation.

Dr. Softic had previously investigated the effects of sugar supplementation when comparing mice that ate a diet of regular chow versus a high-fat diet. That research, published in the Journal of Clinical Investigation in 2017, found that with a chow-fed diet, mice showed no major physiological differences between fructose and glucose supplementation. However, mice who consumed a high-fat diet with fructose became more obese, glucose-intolerant, and developed hepatomegaly, despite taking in an amount of calories similar to mice supplemented with glucose.

“These results were quite interesting, so they prompted us to take this study a step further and learn more about fructose’s effect on fat metabolism,” Dr. Softic said.

Next steps, he said, will involve researching whether fructose or its metabolizing enzymes can directly interact with transcriptional regulators of DNA to turn off the genes involved in fat oxidation.