Fructose and glucose are two common sugars found in many foods and drinks. Although they contain the same amount of calories, new research suggests that the brain responds to them in very different ways.
Scientists at the Monell Chemical Senses Center discovered that fructose and glucose communicate with the brain through separate pathways between the gut and the brain. Their findings indicate that these differences can influence food and drink preferences and could help explain why certain sweetened products are especially attractive.
The study, published June 10 in the journal Neuronidentified a specific signaling pathway that allows fructose to communicate with the brain. In experiments with mice, the researchers found that this pathway was much less effective than that used by glucose in reducing the activity of neurons associated with hunger.
“This work adds to our growing understanding of how modern diets, especially those high in fructose or high-fructose corn syrup, interact with the neural systems involved in appetite,” said lead author and Monell Fellow Amber Alhadeff, PhD.
How fructose and glucose affect hunger neurons
To investigate how sugars influence the brain, researchers recorded neuronal activity in mice after exposure to fructose and glucose.
The team found that fructose increased levels of the gut hormone PYY. That hormone then sends signals through the vagus nerve, leading to a modest reduction in the activity of agouti-related protein (AgRP) neurons, which play an important role in driving hunger. When the researchers disrupted this pathway, fructose could no longer affect those neurons.
Glucose produced a very different response. According to the researchers, it did not depend on the same PYY-Y2 vagus nerve pathway. Instead, glucose strongly suppressed the activity of AgRP neurons, resulting in a much greater effect on hunger-related brain signaling.
The type of sugar influenced food preferences
Although fructose and glucose produced similar short-term effects on food intake, the mice eventually developed preferences that corresponded to the degree of inhibition of AgRP neurons triggered by each sugar.
The researchers also examined high-fructose corn syrup (HFCS), a widely used sweetener made from a combination of fructose and glucose. The mice showed a preference for HFCS, and the sweetener suppressed AgRP neuronal activity more strongly than fructose alone.
According to the researchers, this stronger effect on hunger-related neurons may help explain why foods and beverages containing HFCS may be particularly appealing.
Challenging assumptions about calories and hunger
The results call into question a long-held assumption that AgRP neurons primarily track calorie intake, regardless of where those calories come from.
Instead, the findings suggest that these hunger-related neurons can distinguish between different sugars and respond through separate biological pathways. Although fructose and glucose provide the same amount of energy, the mice’s brains processed them differently.
The study highlights the complexity of nutrient sensing in the body and suggests that even simple sugars can have different effects on the gut, brain and behavior.
This research was supported by grants R01DK131558, DP2AT011965, R01DK116004, F31DK13558, and S10OD030354 from the National Institutes of Health; the American Heart Association; the New York Stem Cell Foundation; the Klingenstein Fund; the Simons Foundation, Pew Charitable Trusts, the Penn Institute for Diabetes, Obesity and Metabolism; the Hearst Scholarship and the Monell Chemical Senses Center.