Fructose and glucose are two common sugars found in many foods and drinks. Even though 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 have discovered that fructose and glucose communicate with the brain through separate gut-brain pathways. Their findings show that these differences can influence food and beverage preferences and may help explain why certain sweetened products are particularly appealing.
The study was published June 10 in the journal neuronidentified a specific signaling pathway that allows fructose to communicate with the brain. In experiments with mice, researchers found that this pathway was much less effective than the one used by glucose at reducing the activity of hunger-related neurons.
“This study furthers our understanding of how modern diets, particularly those high in fructose and high-fructose corn syrup, interact with the nervous system involved in appetite,” said lead author and Monell member Dr. Amber Alhadeff.
Effects of fructose and glucose on starved neurons
To investigate how sugar affects the brain, researchers recorded neural activity in mice after exposure to fructose and glucose.
The research team found that fructose increases levels of the intestinal hormone PYY. The hormone then sent a signal through the vagus nerve, slightly reducing the activity of agouti-related protein (AgRP) neurons, which play a major role in triggering starvation. When researchers disrupted this pathway, fructose was no longer able to affect those neurons.
Glucose caused a very different response. They did not rely on the same PYY-Y2 vagal pathway, the researchers said. Instead, glucose strongly suppressed the activity of AgRP neurons, resulting in a much greater impact on hunger-related brain signaling.
Types of sugar affect food preferences
Although fructose and glucose had similar short-term effects on food intake, mice eventually developed preferences that corresponded to the degree of AgRP neuron inhibition caused by each sugar.
The researchers also looked at high fructose corn syrup (HFCS), a widely used sweetener made from a combination of fructose and glucose. Mice showed a preference for HFCS, and the sweetener suppressed AgRP neuron activity more strongly than fructose alone.
This powerful effect on hunger-related neurons may help explain why foods and beverages containing HFCS are particularly appealing, the researchers say.
Challenging assumptions about calories and hunger
This result calls into question the long-held assumption that AgRP neurons primarily track caloric intake, regardless of where the calories come from.
Rather, the findings suggest that these hunger-related neurons can distinguish between different sugars and respond through different biological pathways. Although fructose and glucose provided the same amount of energy, the mouse’s brain processed them differently.
This study highlights the complexity of nutrient sensing in the body and suggests that even simple sugars can have distinct 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. American Heart Association. New York Stem Cell Foundation. Klingenstein Foundation. Simons Foundation, Pew Charitable Trusts, and Penn Institute for Diabetes, Obesity, and Metabolism. Hearst Fellowship, and Monell Chemosensory Center.
