An incredible study published in Nature has reported the discovery of a novel gut-brain pathway that drives our appetite for fatty foods. The research found cells in our gut sense the presence of fat in food and can directly talk to parts of our brain to make us keep eating.
As humans, our deep-seated preference for high-calorie, fatty foods is a product of evolution. To avoid starvation, our bodies are geared to make us overeat when we get the opportunity to indulge in a fatty meal.
A number of different mechanisms switch on when we eat fatty food, from gut hormones regulating satiety to taste receptors triggering dopamine-fueled feelings of pleasure. However, in our modern world of unlimited access to food, these animalistic drives often result in obesity and metabolic disease.
“We live in unprecedented times, in which the overconsumption of fats and sugars is causing an epidemic of obesity and metabolic disorders,” said first author Mengtong Li. “If we want to control our insatiable desire for fat, science is showing us that the key conduit driving these cravings is a connection between the gut and the brain.”
Two years ago a landmark study discovered a direct pathway between the gut and brain that communicated the presence of sugar in the intestine. This signaling pathway transcended any communication of sweetness between the mouth and the brain, suggesting our guts may be controlling what we eat in more direct ways than were previously thought. This new research follows on from those prior findings to explore whether similar pathways between the gut and brain communicate responses to fatty foods.
After training mice to have a preference for water with added fat, and genetically modifying the animals to remove their ability to send taste signals from the tongue to the brain, the researchers homed in on a part of the brainstem that seemed to be sparking up in response to fat. Neurons were found to activate in a brainstem region called the caudal nucleus of the solitary tract (cNST).
Following the lines of neural communication the researchers detected activity in the vagus nerve carrying messages to the cNST. Because the vagus nerve is the main communication link between the gut and the brain, this was the first clue that the gut could be directly talking to the brain about fat.
The next step was to zoom in on the gut and figure out how it was sending fat-related signals to the vagus nerve. Here, the team discovered two groups of cells lining the intestines that appeared to be talking to vagal neurons when fat reached the gut.
“One group of cells functions as a general sensor of essential nutrients, responding not only to fat, but also to sugars and amino acids,” explained Li. “The other group responds to only fat, potentially helping the brain distinguish fats from other substances in the gut.”
So the pathway from the gut to the vagus nerve to the brain was clear, but how powerfully was it controlling the animals’ appetite for fat? To test this the researchers used a drug to block signaling from these intestinal cells to the vagus nerve.
When the pathway was blocked the animals lost their appetite for fat. Further verifying the importance of this communication pathway, the researchers blocked communication from the vagus nerve to the cNST, and blocked neuron activity in the CNST. In both experiments the animals again lost their craving for fat.
“These interventions verified that each of these biological steps from the gut to the brain is critical for an animal’s response to fat,” said Li. “These experiments also provide novel strategies for changing the brain’s response to fat and possibly behavior toward food.”
Charles Zuker, a researcher working on both this study and the 2020 sugar study, said the discovery of this novel gut-brain pathway offers the opportunity to develop anti-obesity treatments that block this signaling mechanism. Instead of trying to suppress appetite hormones, or change the way our brains respond to the pleasure of food, this points to a new way to stop the body from excessively eating fatty foods.
“Our research is showing that the tongue tells our brain what we like, such as things that taste sweet, salty or fatty,” said Zuker. “The gut, however, tells our brain what we want, what we need.”
The new study was published in Nature.
Source: Columbia University
