January 26, 2024 – The craving feels inevitable and unavoidable – you rise up, go to the kitchen, open the fridge or pantry and think. Even though you remember to take into consideration a chunk of fruit or some protein, your eyes decide on the potato chips and cookies.
If fats and sugars sometimes seem irresistible, you're not alone. A new study Published in Cell metabolism, based on work by researchers on the Monell Chemical Senses Center in Philadelphia, shows that we’ve two separate but parallel pathways for craving fat and sugar, sending signals from the gut to the brain that fireplace up our dopamine reward centers . Even more, the mix of those pathways seems to stimulate our desire to eat greater than usual.
“In recent years, we’ve developed latest tools to review the vagus nerve as a communication pathway between the gut and the brain to regulate food intake. In this study, we used these tools to grasp a straightforward query that we imagine is at the center of the obesity epidemic: Why will we eat foods we all know are bad for us?” said study author Guillaume de Lartigue, PhD, a neuroscientist at Monell who studies the neurobiology of eating.
Specifically, the vagus nerve sends internal sensory information via nerve cells in the gut – rather than taste cells in the mouth – which plays a key role in making fats and sugars attractive. Ultimately, the research could shed light on what controls “motivated” eating behavior and how an unconscious desire to consume fats and sugars can counteract dieting efforts.
“We suspect that this gut mechanism explains, at least in part, why we eat too much food that is rich in fats and sugars,” said de Lartigue. “This sheds light on the cause of overeating and why dieting is so difficult. “We literally have to fight the subconscious urge to eat that donut.”
Understanding gut-brain dynamics
De Lartigue and colleagues used new, cutting-edge neuroscience technologies to directly manipulate fat or sugar neurons in the vagus nerve system of mice. They found that both types of neurons cause a release of dopamine in the reward center of the brain. They also discovered two specialized vagal nerve pathways—one for fats and one for sugars—that start in the gut and send information about what was eaten to the brain. This creates the conditions for food cravings.
To understand how fats and sugar affect the brain, the researchers then stimulated the vagus nerves in the gut with light. This caused the mice to actively search for food to activate these circuits. This showed that fat and sugar are sensed by separate neurons and activate different reward circuits, increasing cravings.
In addition, the research team found that activating both the fat and sugar cycles created a synergy, like a “double whammy on the brain,” de Lartigue said. The combination of fat and sugar led to a significantly greater release of dopamine, which ultimately led to overeating in the mice.
Although the results still need to be studied in more detail in mice and humans, the results are important for current weight-related research as well as for treatments such as semaglutide and tirzepatide, which belong to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists and are sold under brand names such as Ozempic, Wegovy and Mounjaro.
“The role of gut signals in controlling food intake has a long history, and the most effective therapies currently available to suppress appetite and reduce body weight (GLP-1 agonists and gastric bypass surgery) are based on altering such signals. said Hans-Rudolf Berthoud, PhD, professor of neurobiology and nutrition at the Pennington Biomedical Research Center at Louisiana State University.
“The sugar-fat combination is a very powerful appetite stimulant in mice and will also explain diet-induced obesity in humans,” he said. “Learning more about gut-brain communication could ultimately lead to the development of new and more specific therapies to combat obesity and its many complications.”
What does this mean for your gut?
These separate but parallel fat and sugar cycles may shed light on why dieting can be so challenging, de Lartigue said. The human brain is likely to seek out combinations high in fat and sugar, regardless of conscious efforts to reduce them. Because this gut-brain communication occurs below the level of consciousness, you may subconsciously crave these foods, he noted.
“The most immediate next question is to understand whether inactivating these pathways could prevent animals or humans from developing a preference for foods high in fat and sugar,” said Nicholas Betley, PhD, associate professor of biology at the University of Pennsylvania .
“This is a difficult experiment because these cells are likely involved in detecting other signals in the body. However, if these pathways could be inactivated, one would expect that cake and ice cream after dinner would not be as tempting,” he said. “Of course this is a wish at the moment, but it would be the direction in which these findings could lead us.”
If the pathways could be controlled with drugs, some drugs could target consumption of sugary and fatty foods, he said. Future research could also potentially open doors to treating pathological behaviors such as binge eating, overeating and anorexia.
“The dopamine pathways can also be used to promote healthy behaviors,” Betley said. “We recently published on the effects of exercise on dopamine levels, suggesting that more exercise can change your microbiome and increase the dopamine rush you get from exercise. So these gut-brain communication pathways could also be used to reinforce healthy behaviors – and our bodies are designed to enable this too.”
What does this mean for your brain?
Targeted control and regulation of the reward circuits between the gut and the brain could offer a novel approach to curbing unhealthy eating habits. “Ultimately, understanding the mechanisms behind your motivation to eat fats and sugars is the first step,” de Lartigue said. Even when faced with a tempting treat, people could make healthier choices based on personalized intervention plans.
“It is becoming increasingly apparent that these mechanisms play a major role in controlling eating behavior and food choice. Given the success of gut-derived peptides (such as Wegovy and Ozempic) in weight loss, it is important to understand the gut-brain axis to develop more effective treatments and strategies for weight loss and weight maintenance,” said Alexandra DiFeliceantonio, PhD, a Neuroscientist and assistant professor at the Fralin Biomedical Research Institute at Virginia Tech Carilion.
“Most foods high in sugar and fat are highly processed or ultra-processed foods, and these combinations rarely occur in nature,” she said. “Our lab is working to understand what other properties of processed and highly processed foods make them so compelling.”
These neural pathways could also offer latest insights into mental health and targeted treatments for brain health.
“Not only is gut-to-brain signaling critical for controlling metabolism and food intake, but recent evidence also suggests an important role for the gut in cognition and brain health,” said Scott Kanoski, PhD, University co-director of the Southern California Diabetes and Obesity Research Institute and president of the Society for the Study of Ingestive Behavior.
“We recently identified a role for the vagus nerve in promoting learning and memory function,” he said. “Meals are important events that need to be enshrined in memory because such memories will guide more efficient foraging and consumption strategies in the future.”
In other words, sugar and fat signals can activate specific circuits within the brain's memory systems. Further research could show whether behavioral changes or medications may improve overall health.
“There is a surprising amount of evidence about how the brain and body communicate quickly to influence our behavior – showing us that our overall health and our mental health are influenced by what we consume, how we treat our bodies and whether we exercise drift.” Betley said. “It re-emphasizes the importance of holistic medicine for our overall well-being, as this communication between our brain and our body is likely to influence all aspects of our health.” And while all of those studies will enable higher production of medication for a particular condition, healthy ones can Food and caring for our bodies will be just as vital in stopping disorders and illnesses.”