Researchers from the Monell Center have found that common dietary sugars, fructose and glucose, despite having the same caloric value, interact with the brain via distinct gut-brain pathways, potentially influencing our food and drink choices. In mice, the team identified a specific gut-brain signaling route through which fructose communicates with the brain. This pathway proved considerably less effective than the one used by glucose in reducing the activity of neurons linked to hunger. The findings of their investigation are published in the journal Neuron.
“This work adds to our growing understanding of how modern diets, particularly those high in fructose or high-fructose corn syrup, engage with the appetite-regulating nervous system,” explains Amber Alhadeff, co-lead author of the study from the Monell College.
By monitoring neural activity in mice, the researchers observed that fructose triggered an increase in the gut hormone PYY. This hormone then moderately suppressed the activity of neurons containing agouti-related peptide (AgRP) – crucial brain cells responsible for hunger signals – via the vagus nerve. Disrupting this specific pathway neutralized fructose’s effect on these neurons. In contrast, the researchers noted that glucose did not rely on the same PYY-Y2 pathway involving the vagus nerve, and instead caused a strong inhibition of AgRP neuron activity.
The researchers discovered that while both sugars had a similar short-term impact on how much food mice consumed, the animals developed food preferences linked to the degree of AgRP inhibition associated with each sugar.
The scientists also examined high-fructose corn syrup (HFCS), a widely used food additive composed of both fructose and glucose. Mice showed a preference for HFCS, and it suppressed AgRP neuron activity more robustly than fructose alone. According to the researchers, this could help explain why foods and beverages containing HFCS appear particularly appealing to some individuals.
These results challenge the long-held notion that AgRP neurons, which signal hunger, track calorie intake irrespective of the nutrient source. Instead, this research suggests that these neurons can differentiate between sugars and respond to them through different biological mechanisms. Even though fructose and glucose offer the same number of calories, the animals’ brains processed them differently.
These new findings highlight the intricate nature of nutrient perception, demonstrating that even simple sugars can exert varied effects on the gut, brain, and ultimately, our behavior.
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