Gut-brain circuit for sugar and fat cravings could impede dieting

US researchers have revealed why the combination of fat and sugar is so irresistible, finding that consuming both delivers a “1-2 punch” to the brain’s reward system.

The study, done in mice, reveals separate fat and sugar craving pathways that originate in the gut, and that activating both of these pathways at the same time triggers the desire to overeat.

The findings shed light on why dieting can be so challenging: human brains may be programmed to seek out high-fat, high-sugar combinations, regardless of conscious efforts not to.

Guillaume de Lartigue, a scientist at the Monell Chemical Senses Center in the US and lead author of a paper in Cell Metabolism, says that the reason 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,” says de Lartigue.

To better understand how food influences our choices, de Lartigue and collaborators studied the vagus nerve in mice. This nerve is known to send sensory information from the gut to the brain about the nutritional value of food.

They discovered 2 dedicated vagus nerve pathways – one population of sensory neurons for fats and the other for sugars – that originate in the gut and sense and relay information about their presence to the brain.

They found that directly activating fat or sugar neurons in the vagus nerve system resulted in dopamine release in the mice brain’s reward centre and increased feeding behaviour.

Strikingly, activating both the fat and sugar circuits at the same time created an even more powerful effect.

De lartigue cell metab image racetrack jan 2024 850
In this illustration, fat, sugar, and the combination of both (chocolate) navigate a gut-brain maze. The blue path represents the sugar route, the green path signifies the fat route, and the yellow path represents the combined impact of fats and sugars. Each path leads to the brain, but the combined route has a greater impact, triggering heightened dopamine release in the reward circuits, emphasizing the synergistic effect of fat-sugar combinations on neural responses. Credit: Isadora Braga, de Lartigue lab, Monell Center

“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,” says de Lartigue.

The authors say that their work provides new insights into the complex sensory circuitry that mediates motivated behaviour and suggests that a subconscious internal drive to consume diets high in both fat and sugar might hinder conscious dieting efforts.

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

So, targeting and regulating these gut-brain reward circuits could potentially offer a new way 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,” says de Lartigue. 

“This research unlocks exciting possibilities for personalised interventions that could help people make healthier choices, even when faced with tempting treats.”

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