Fructose and glucose have different effects on satiety

In their experiments on mice, the team discovered a specific pathway from the gut to the brain through which fructose interacts with the central nervous system. However, this mechanism is significantly less effective than glucose in suppressing the activity of hunger-related neurons.

The researchers recorded neural activity and observed the following pattern. Fructose triggered an increase in the level of the gut hormone PYY. Next, this hormone moderately suppressed the activity of agouti-related protein (AgRP) neurons, key brain cells involved in the formation of hunger, through the vagus nerve. When the researchers disrupted this pathway, the effect of fructose on the neurons ceased.

Glucose, on the other hand, did not involve the PYY-Y2 route through the vagus nerve, but it did cause a significant suppression of AgRP neuron activity. However, in the short term, both sugars had a similar effect on the amount of food consumed by the mice. However, over time, the animals developed food preferences based on how much each sugar suppressed the activity of AgRP neurons.

The team also studied high-fructose corn syrup (HFCS), a common food additive that contains a mixture of fructose and glucose. The mice showed a preference for HFCS. Interestingly, HFCS had a stronger effect on suppressing the activity of AgRP neurons compared to pure fructose. This finding may explain why foods and beverages containing HFCS are particularly appealing to many people.

The findings challenge the long-held belief that AgRP neurons track calorie intake regardless of the nutrient source. These neurons discriminate between sugars and respond to them through distinct biological mechanisms. Despite having the same caloric content, the brains of the animals responded differently to fructose and glucose. These findings highlight the complexity of nutrient perception. Even simple compounds like sugars have varying effects on the gut, brain, and behavior.