Dieters who struggle with cravings for high-fat foods may blame their tongues: the deliciousness of butter or ice cream is so hard to resist. But a new study has found a whole new connection between our intestines and our brains, one that drives fat cravings.
By studying rats, American scientists found that fat entering the intestine triggers a signal. This signal is transmitted through nerves to the brain, prompting people to want to eat high-fat foods. The study, recently published in Nature, raises the possibility of a way to disrupt this gut-brain connection to help discourage unhealthy choices and address the growing global health crisis caused by overeating.
“We are living in an unprecedented era where the overconsumption of fat and sugar is leading to an epidemic of obesity and metabolic disorders.” First author Mengtong Li (phonetic), a postdoctoral researcher in Dr. Charles Zuker’s lab at Columbia University’s Zuckerman Institute, said, “Science tells us that the key channel is the connection between the gut-brain if we want to control our desire for fat.”
The researchers found that glucose activates a special gut-brain circuit, which connects to the brain in the presence of sugar in the gut. In contrast, artificial sweeteners do not have this effect, which may explain why sugar-free sodas leave us feeling less satisfied.
“Our research shows that the tongue tells the brain what we like to eat, such as sweet, salty or greasy.” Zuker, who is also a professor of biochemistry, molecular biophysics and neuroscience at Columbia University’s Vagelos School of Medicine, said, “And the gut tells the brain what we want and need.”
Mengtong Li wanted to explore how rats respond to dietary fats: all animals must consume lipids and fatty acids in order to sustain life.
She gave the rats a bottle of water containing dissolved fats (including a soybean oil component) and a bottle of water containing sweet substances that are known not to affect the gut. After a few days, the rodents developed a strong preference for the fat-rich water. They developed this preference even after scientists genetically modified the rats to eliminate their ability to taste fat with their tongues.
“Even though these animals couldn’t taste the fat, they were driven to eat it.” Zuker said.
The researchers reasoned that fat must activate a specific brain circuit that drives the animals’ behavioral response to fat. To find this circuit, Mengtong Li measured the rats’ brain activity while feeding them fat. At this time, neurons in a specific region of their brainstem, the nucleus tractus solitarius (cNST), were active. This is interesting because the cNST is also related to the neural basis of sugar preference previously identified in the lab.
After identifying the biological mechanisms behind the rats’ preference for fat, Mengtong Li took a closer look at the gut itself, specifically the endothelial cells of the gut. She found that two groups of cells send signals to vagal cells in response to fat.
“One group of cells is a universal sensor of essential nutrients, responding not only to fat but also to sugar and amino acids.” Mengtong Li said, “The other group only responds to fat, which may help the brain distinguish fat from other substances in the gut.”
Then Mengtong Li took an important step forward by blocking the activity of these cells with a drug that turned off signals from both groups of cells, preventing the vagus nerve from responding to the fat in the gut. She then used genetic techniques to inactivate the vagal cells themselves or the neurons in the cNST. In both cases, the rats lost their appetite for fat.
“These interventions confirm that every biological step from the gut to the brain shows that the animal’s response to fat is critical.” Mengtong Li said, “These experiments also provide new strategies for altering the brain’s response to fat and its behavior toward food.”
Since 1980, global obesity rates have nearly doubled. Today, nearly 500 million people have diabetes. “The over-consumption of cheap, highly processed foods rich in sugar and fat is having a devastating impact on human health, especially among low-income populations.” Zuker said, “The more we understand the biological mechanisms of how these foods hijack the tastebuds and gut-brain axis, the better chance we have to intervene.”
