This shows a head made of candy.
This finding sheds light on why dieting can be so challenging. Credit: Neuroscience News

Gut-Brain Network for Sugar and Fat Cravings Discovered

Summary: Researchers identified distinct neural pathways in the brain for fat and sugar cravings. This research reveals that separate circuits in the vagus nerve, originating in the gut, communicate information about consumed fats and sugars to the brain, triggering dopamine release in the brain’s reward center.

The study found that activating both fat and sugar circuits simultaneously leads to a significant increase in dopamine release and overeating in mice. This discovery provides key insights into why high-fat, high-sugar foods are so irresistible and why dieting can be challenging, opening new avenues for developing anti-obesity strategies.

Key Facts:

  1. Distinct gut-brain pathways are activated by fats and sugars, leading to cravings.
  2. Combining fats and sugars in the diet triggers an amplified dopamine release and subsequent overeating.
  3. The research could lead to new strategies for combating unhealthy eating habits by targeting these gut-brain reward circuits.

Source: Monell Chemical Senses Center

Understanding why we overeat unhealthy foods has been a long-standing mystery. While we know food’s strong power influences our choices, the precise circuitry in our brains behind this is unclear.

The vagus nerve sends internal sensory information from the gut to the brain about the nutritional value of food. But, the molecular basis of the reward in the brain associated with what we eat has been incompletely understood. 

Now, a new study published in Cell Metabolism by a team from the Monell Chemical Senses Center, unravels the internal neural wiring, revealing separate fat and sugar craving pathways, as well as a concerning result: Combining these pathways overly triggers our desire to eat more than usual.

“Food is nature’s ultimate reinforcer,” said Monell scientist Guillaume de Lartigue, PhD, lead author of the study.

“But why fats and sugars are particularly appealing has been a puzzle. We’ve now identified nerve cells in the gut rather than taste cells in the mouth are a key driver.  We found that distinct gut-brain pathways are recruited by fats and sugars, explaining why that donut can be so irresistible.”

Ultimately this research provides insights on what controls “motivated” eating behavior, suggesting that a subconscious internal desire to consume a diet high in both fats and sugar has the potential to counteract dieting efforts. 

The team used cutting-edge technology to directly manipulate fat or sugar neurons in the vagus nerve system and demonstrated that both types of neurons cause a dopamine release in the brain’s reward center in mice. They discovered two dedicated vagus nerve pathways: one for fats and another for sugars. These circuits, originating in the gut, relay information about what we have eaten to the brain, setting the stage for cravings. 

To determine how fats and sugars affect the brain, the team stimulated gut vagal nerves with light. This, in turn, induced the mice to actively seek stimuli, in this case food, that engage these circuits. The results indicated that sugar and fat are sensed by discrete neurons of the vagus nerve and engage parallel but distinct reward circuits to control nutrient-specific reinforcement. 

But the story doesn’t end there. The team also found that simultaneously activating both the fat and sugar circuits creates a powerful synergy.

“It’s like a one-two punch to the brain’s reward system,” said de Lartigue. “Even if the total calories consumed in sugar and fats stays the same, combining fats and sugars leads to significantly more dopamine release and, ultimately, overeating in the mice.”

This finding sheds light on why dieting can be so challenging. Human brains may be subtly programmed to seek out high-fat, high-sugar combinations, regardless of conscious efforts to resist.

“The communication between our gut and brain happens below the level of consciousness,” said de Lartigue. “We may be craving these types of food without even realizing it.”

The team predicts that this line of research offers hope for future development of anti-obesity strategies and treatments. Targeting and regulating gut-brain reward circuits could offer a novel approach to curb unhealthy eating habits.

“Understanding the wiring diagram of our innate motivation to consume fats and sugars is the first step towards rewiring it,” said de Lartigue.  “This research unlocks exciting possibilities for personalized interventions that could help people make healthier choices, even when faced with tempting treats.”

de Lartigue’s co-authors are Molly McDougle, Alan de Araujo, Arashdeep Singh, Mingxin Yang, Isadora Braga, Vincent Paille, Rebeca Mendez-Hernandez, and Brandon Warren, all from the Monell Center; Macarena Vergara, Abhishek Gour, Abhisheak Sharma, and Nikhil Urs, all from the University of Florida, and Lauren N. Woodie, University of Pennsylvania. 

Funding: The research was supported by the National Institutes of Health (R01 DK116004, R01 Q15, DK094871, F31 DK1311773); an AHA postdoctoral fellowship and grants from the SanteDige Foundation and Phillip Foundation. 

About this neuroscience research news

Author: Karen Kreeger
Source: Monell Chemical Senses Center
Contact: Karen Kreeger – Monell Chemical Senses Center
Image: The image is credited to Neuroscience News

Original Research: Open access.
Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating” by Guillaume de Lartigue et al. Cell Metabolism


Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating


  • Intestinal fats and sugars are sensed by distinct vagal populations
  • Nutrient-sensing vagal sensory neurons are necessary and sufficient for reinforcement
  • Both fat and sugar cause dopamine release by engaging separate central reward circuits
  • Combining fat and sugar supra-additively increases dopamine efflux and eating


Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars.

Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of nutrients, we demonstrate the existence of separate gut-brain circuits for fat and sugar sensing that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases nigrostriatal dopamine release and overeating compared with fat or sugar alone.

This work provides new insights into the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.

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