Study reveals how excess carbohydrates may contribute to metabolic dysfunction

By studying how cells from healthy normal weight and overweight participants broke down carbohydrates in real time, researchers have found clues about what triggers metabolic distress, according to new research published in the American Journal of Physiology— Endocrinology and Metabolism.

A high body mass index (BMI) is closely correlated with insulin resistance and type 2 diabetes. For decades, nutrition guidelines have emphasized the necessity of decreasing intake of dietary fats. Yet, even as studies demonstrate ties between foods laden with simple carbohydrates and metabolic dysfunction, much remains unknown about how the body processes large amounts of carbohydrates eaten in a single meal.

To study how cells break down carbohydrates in real time, researchers from Brigham and Women’s Hospital and Boston Medical Center studied healthy normal weight and healthy overweight participants as they consumed excess carbohydrates. Their findings revealed that excess carbohydrates can contribute to metabolic dysfunction by blocking the synthesis of important antioxidants and demonstrated that high insulin levels under such circumstances can exacerbate the issue.

Researchers tracked the activity of the electrons in the cells of 24 non-diabetic participants who consumed large quantities of carbohydrates in proportion to their weight. They found evidence, more pronounced in participants with high BMIs, that the cells were using electrons from glutathione, a “master antioxidant,” to help store excess carbohydrates as fats. This supported their hypothesis that overconsuming carbohydrates may contribute to metabolic distress by limiting antioxidant synthesis in the body.

When the researchers analyzed biopsies from the participants, they confirmed that in participants with high BMIs, changes in the fat tissue that occurred during the study represented a form of metabolic stress often seen in insulin resistance and type 2 diabetes.

The researchers demonstrated that insulin, which lowers blood sugar by increasing its uptake by the cells, may contribute to metabolic distress when cells are unprepared to process such a large amount of carbohydrates. When an individual consumes carbohydrates in excess, cells break down the molecules and resynthesize them into fats through a “reduction” process that uses electrons. The researchers hypothesized that during fat synthesis, the cells may be “taking electrons away” from other metabolic activities, like the production of antioxidants, which are important molecules that help protect the body from deterioration.

Going forward, the researchers hope to further examine metabolic processes in those with normal versus high BMIs using the quantitative approach from this study, which is common in biochemistry research but not often used to study acute events, like overfeeding, in humans.