Separate Circuits, Stronger Cravings: How Your Brain Makes You Crave Fat and Sugar

Our brains have separate circuits for processing fat and sugar, influencing our cravings. This study in Cell Metabolism reveals distinct vagus nerve pathways for each. Sugar activates neurons linked to the liver, while fat targets the intestines. Both lead to dopamine release, but combining fat and sugar creates a stronger reward, making it harder to resist overeating these tempting foods. The subconscious nature of these signals further complicates weight management.

Key Points

• Separate Vagal Pathways for Fats and Sugars: The study reveals that the vagus nerve contains distinct populations of sensory neurons. These populations respond specifically to fats or sugars, suggesting separate neural pathways for sensing these macronutrients in the gut.

• Fat and Sugar Activate Different Reward Circuits: The research shows that the vagal signals from fat- and sugar-sensing neurons activate distinct circuits in the brain. These circuits ultimately converge on the dopamine system in the dorsal striatum, but they do so through separate pathways.

• Combined Fat and Sugar Leads to Stronger Reward: When both fat and sugar pathways are activated, the reward response is stronger than with either alone. This translates to increased dopamine release and greater food intake, potentially explaining why we find combinations of fat and sugar so appealing.

• Chemosensory Neurons Play a Critical Role: The study focuses on chemosensory neurons in the nodose ganglia that detect nutrients in the gut. These neurons are shown to be essential for sugar and fat reinforcement, highlighting their role in driving motivated feeding behavior for specific nutrients.

• Hepatic Portal Vein and Sugar Sensing: The vagal circuit for sugar sensing innervates the hepatic portal vein, which receives blood rich in sugar from the intestines after a meal. This suggests a potential role for this pathway in regulating blood sugar levels and food intake.

• Dopamine System and Motivation to Eat: The nigrostriatal dopamine pathway is a key player in motivated behaviors, including eating. This study demonstrates that separate gut-brain circuits for sugar and fat ultimately influence dopamine release in the dorsal striatum, thereby regulating motivation to consume these nutrients.

• Subconscious Drive for Obesogenic Diets: The signals from the gut-brain circuits operate below conscious awareness. This suggests that the urge to consume high-fat, high-sugar foods may be subconscious, making it challenging to resist them solely through willpower.

Obesity and the Brain's Reward System for Fats and Sugars

This study investigates how the brain differentiates between fats and sugars to control our desire to eat. It reveals separate gut-brain circuits for these macronutrients, potentially explaining why diets high in both are so difficult to resist.

The Vagus Nerve and Dopamine

The vagus nerve carries messages from the gut to the brain about nutrients. The striatum in the brain is involved in motivated behaviors. When we taste something, dopamine is released in the ventral striatum. When nutrients reach the intestine, dopamine is released in the dorsal striatum (DS), prioritizing calorie intake over taste. Studies show that vagal sensory neurons are important for this process. Activating these neurons is rewarding, and animals seek such stimulation.

Do Fats and Sugars Use the Same Pathway?

Previous research hasn't definitively answered if fats and sugars use the same vagus nerve pathway to signal the brain. Vagal sensory neurons are diverse and have various functions. This study aimed to see if specific vagal populations sense fats and sugars and whether they use separate brain circuits.

New Technique for Studying Gut-Brain Circuits

The researchers developed a new technique using genetically modified mice to monitor calcium activity in vagal sensory neurons. This allowed them to see which neurons responded to sugar or fat infusions in the gut.

Separate Vagal Pathways for Fats and Sugars

The study found that fats and sugars activate distinct groups of vagal sensory neurons. There was little overlap, with some neurons responding strongly to fat and others to sugar. This suggests separate gut-brain circuits for these macronutrients.

Fat and Sugar Activate Different Reward Circuits

The researchers then investigated how these separate vagal signals affect the brain's reward system. They found that both fats and sugars caused dopamine release in the dorsal striatum, but they did so through distinct circuits. This means the brain treats fats and sugars differently in terms of reward.

Combined Fat and Sugar Effects

Finally, the researchers examined the effect of consuming both fat and sugar. They found that when both fat and sugar pathways were activated, dopamine release and food intake increased more than with either fat or sugar alone. This suggests that combining fats and sugars creates a stronger rewarding effect, potentially making it harder to resist overeating such foods.

Identifying Chemosensory Neurons

The study focused on chemosensory neurons in the nodose ganglia (NG) that respond to chemicals, including nutrients. These neurons have projections to the gut and the brainstem. The researchers used a new approach to target these specific neurons and investigate their role in food reinforcement.

Function of Chemosensory Neurons

Chemosensory NG neurons were previously identified but their function remained unclear. This study demonstrates that they play a key role in signaling nutrient reinforcement. When activated by sugar or fat, they trigger gut-brain reward circuits that promote motivated feeding behavior for specific nutrients.

Separate Circuits for Sugar and Fat

The researchers used FosTRAP, a technique to genetically target neurons activated by specific stimuli, to differentiate between sugar- and fat-sensing vagal circuits. They found that these circuits have distinct properties:

• Innervation: Sugar-responsive neurons innervate the hepatic portal vein, while fat-responsive neurons innervate the duodenum.

• Necessity: Ablation of sugar-responsive neurons blocked sugar reinforcement, and vice versa for fat.

• Brain Activity: Activation of separate circuits led to downstream activity in the nigrostriatal dopamine pathway.

Sugar and the Hepatic Portal Vein

The sugar-sensing vagal circuit innervates the hepatic portal vein, which receives blood from the intestines rich in sugar after a meal. This suggests a role for this pathway in regulating blood sugar levels and food intake.

Markers for Fat- and Sugar-Sensing Neurons

The study highlights the challenge of identifying specific markers for fat- and sugar-sensing vagal neurons. While previous research pointed to CCK receptors, these are expressed in many NG neurons responding to both sugar and fat. Future studies are needed to identify more precise markers for these neuron populations.

The Nigrostriatal Dopamine Pathway

The nigrostriatal circuit is essential for motivated behaviors, including eating. Dopamine release in the DS is a key signal for reward and motivation to eat. This study shows that separate gut-brain circuits for sugar and fat converge on the nigrostriatal dopamine pathway.

Reduced Overlap Along the Circuit

The researchers observed a reduced overlap in response to repeated nutrient infusions as signals travelled from the gut to the DS. This may reflect how neurons respond to repeated stimuli or the widespread effects of dopamine on target cells.

Evolutionary Advantages of Separate Circuits

The study proposes that separate circuits for fat and sugar may have provided an evolutionary advantage. In the natural world, high-fat and high-sugar foods are rarely found together. Having distinct circuits for these macronutrients would allow organisms to efficiently locate and consume different energy sources.

Modern Food Environment and Overconsumption

However, the modern food environment is vastly different. Processed foods often combine high levels of both fats and sugars. The study suggests that these foods hijack the separate reward circuits, leading to a stronger overall reward signal and increased motivation to consume them. This may contribute to excessive consumption and obesity.

Human Preference for Fat and Sugar Combinations

Prior research has shown that humans find combined fat and sugar foods more desirable than those containing just one macronutrient. This aligns with the findings of this study, which suggest a neural basis for this preference.

Combined Fats and Sugars: Increased Dopamine Release and Food Intake

The study found that mice consumed more and showed greater dopamine release when offered a combination of fat and sugar compared to single nutrients. This suggests that combining these macronutrients creates a stronger reward effect, potentially making it harder to resist overeating.

Subconscious Drive for Obesogenic Diets

Interoceptive signals from the gut-brain circuits operate below the level of conscious awareness. This implies that the motivation to consume high-fat, high-sugar foods may occur subconsciously, making it difficult to resist through conscious dieting efforts alone.

Therapeutic Implications: Targeting Gut-Reward Circuits

The study's findings suggest that manipulating the gut reward circuits could be a promising avenue for obesity treatment. By influencing these circuits, it might be possible to promote a voluntary reduction in the consumption of obesogenic foods.

Conclusion

This study provides significant insights into the complex mechanisms underlying our desire for high-fat, high-sugar foods. By revealing separate gut-brain circuits for fats and sugars, it sheds light on why these foods are so tempting and why conscious dieting efforts can be challenging. The research paves the way for future exploration aimed at developing strategies to combat obesity by potentially influencing these subconscious reward pathways.

Reference Article

McDougle, M., De Araujo, A., Singh, A., Yang, M., Braga, I., Paille, V., Mendez-Hernandez, R., Vergara, M., Woodie, L. N., Gour, A., Sharma, A., Urs, N., Warren, B., & De Lartigue, G. (2024). Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metabolism. https://doi.org/10.1016/j.cmet.2023.12.014

Image: Cell Metabolism

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