Study finds sugar type changes hunger signals in mice
Monell researchers report that fructose and glucose use different gut-brain routes, changing hunger-related neuron activity in mice.
By Tom Brennan · Health & Medicine Correspondent
3 min read
Fructose and glucose carry the same calories, but a new mouse study found they do not send the same signals to the brain. Researchers at the Monell Chemical Senses Center said the results may help explain why some sweetened foods and drinks, including those with high-fructose corn syrup, can be especially appealing.
The study, published June 10 in Neuron, examined how the two common sugars affect gut-brain communication and hunger-related brain cells. According to Monell, the work challenges the idea that the brain’s hunger system responds only to calorie amount, regardless of the nutrient source.
Senior author Amber Alhadeff, a Monell member, said the findings add to scientists’ understanding of how diets high in fructose or high-fructose corn syrup interact with neural systems tied to appetite.
Different pathways to hunger cells
The researchers recorded neural activity in mice after exposing them to fructose and glucose. They focused on agouti-related protein neurons, known as AgRP neurons, which Monell described as key drivers of hunger.
Fructose raised levels of the gut hormone PYY, the researchers reported. That hormone then signaled through the vagus nerve and produced a limited reduction in AgRP neuron activity.
When the team disrupted that PYY-Y2 vagus nerve pathway, fructose no longer affected those hunger-related neurons, according to Monell. The finding led the researchers to identify that route as a dedicated signaling path for fructose.
Glucose acted through a different mechanism. Monell said glucose did not depend on the same PYY-Y2 vagus pathway and produced a much stronger suppression of AgRP neuron activity than fructose did.
Preferences tracked brain response
The two sugars had similar short-term effects on how much the mice ate, according to the study summary from Monell. Over time, however, the animals developed preferences that matched the strength of AgRP neuron inhibition triggered by each sugar.
The researchers also tested high-fructose corn syrup, a sweetener made with both fructose and glucose. Monell said the mice preferred high-fructose corn syrup, and it reduced AgRP neuron activity more strongly than fructose alone.
According to the researchers, that stronger response in hunger-related brain signaling may be one reason products made with high-fructose corn syrup are appealing. The study did not report human feeding trials.
Calories did not tell the whole story
Monell said the findings suggest AgRP neurons can distinguish between sugar types, even when the sugars provide the same amount of energy. In the mouse experiments, fructose and glucose reached the brain’s appetite circuits through separate biological routes and produced different levels of hunger-neuron suppression.
The research points to a more complex model of nutrient sensing, in which the gut, brain and behavior respond to the identity of a sugar as well as its calories. The paper is titled “Attenuated hypothalamic response to fructose via a dedicated gut-brain pathway.”
Monell said the work was supported by the National Institutes of Health, the American Heart Association, the New York Stem Cell Foundation, the Klingenstein Fund, the Simons Foundation, the Pew Charitable Trusts, the Penn Institute for Diabetes, Obesity, and Metabolism, the Hearst Fellowship and the Monell Chemical Senses Center.
This story draws on original reporting from ScienceDaily.