Fructose and glucose trigger different brain responses
July 14, 2026
Fructose and glucose trigger different brain responses
At a Glance
- Scientists found the sugars glucose and fructose affect hunger-controlling brain cells and food preferences in mice differently.
- The study suggests that similar nutrients can signal to the brain through distinct pathways and have different effects on appetite.
Many foods contain several types of sugars, including glucose and fructose. When people consume these sugars, the human body digests and processes them into energy. Glucose and fructose provide the same amount of energy, measured in calories. But it’s unclear how the two sugars affect the brain cells that influence hunger and appetite.
Studies have shown that when brain cells called agouti-related protein (AgRP) neurons are more active in mice, the mice experience more hunger. When mice consume calories from food, activity in these cells decreases. This has led to the theory that nutrients like glucose and fructose reduce AgRP neuronal activity–and by extension hunger and appetite–equally.
A team of NIH-funded researchers, led by Dr. Amber Alhadeff of the Monell Chemical Senses Center and the University of Pennsylvania, recently tested that theory. They did so by comparing how AgRP neurons in mice respond to fructose versus glucose. This revealed that fructose is sensed by a distinct gut-brain pathway. Their findings were published on June 10, 2026, in Neuron.
The scientists found that AgRP neurons were less active when mice consumed calories from glucose rather than fructose. High-fructose corn syrup, a mixture of fructose and glucose, suppressed AgRP neuron activity more than fructose alone.
Glucose and fructose caused similar reductions in food consumption, but they affected food preferences differently. Mice preferred to drink a liquid sweetened with glucose or high-fructose corn syrup over one containing fructose. This suggests that glucose’s larger effects on AgRP neurons might lead to a preference for foods sweetened with glucose over those containing fructose.
The team also sought to identify the pathways through which fructose transmits signals to AgRP cells. To do so, they looked at how glucose and fructose affect the vagus nerve, which allows the digestive system to communicate with the brain. Consuming fructose activated different vagus nerve cells compared to glucose.
When the scientists tried blocking vagus nerve signaling between the digestive system and the brain, glucose, but not fructose, still suppressed AgRP neuron firing. These results are consistent with prior studies that found glucose-related signals travel to the brain through the spinal cord. They also suggest that fructose-related signals travel to AgRP neurons through the vagus nerve instead of the spinal cord.
The results show that glucose has a larger effect than fructose on brain cells that influence eating behavior. Moreover, fructose-related and glucose-related signals travel to the brain via different routes. The findings highlight the need for further research into how the specific types of sugar added to food influence the way people eat.
“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,” Alhadeff says.
—by Brandon Levy
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- What are overweight and obesity?
References
Attenuated hypothalamic response to fructose via a dedicated gut-brain pathway. McKnight AD, de Araujo A, Hsu FY, Vargas-Elvira AG, Acosta AA, Smith MM, Iwueze W, de Lartigue G, Alhadeff AL. Neuron. 2026 Jun 10:S0896-6273(26)00384-3. doi: 10.1016/j.neuron.2026.05.013. Epub ahead of print. PMID: 42269609.
Funding
NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Complementary and Integrative Health (NCCIH), and Office of the Director (OD); American Heart Association; New York Stem Cell Foundation; Klingenstein Fund and Simons Foundation; Pew Charitable Trusts; Penn Institute for Diabetes, Obesity, and Metabolism; Monell Chemical Senses Center; Hearst Fellowship.
