Summary: Fat entering the intestine releases a signal that is conducted via nerve cells and the brain, which leads to a desire to eat fatty foods.
source: Columbia University
A dieter who struggles with cravings for fatty foods might be tempted to blame their tongue: The delicious taste of butter or ice cream is hard to resist. But new research looking into the source of our appetite has revealed an entirely new relationship between the gut and the brain that drives our craving for fat.
At Columbia University’s Zuckerman Institute, scientists studying mice have found that getting fat into the intestine triggers a signal. This signal, conducted along the nerves of the brain, leads to the desire to eat fatty foods.
Posted on September 7, 2022 in temper natureThe new study raises the possibility of interfering with the communication between the gut and the brain to help prevent unhealthy choices and address the growing global health crisis caused by overeating.
“We are living in unprecedented times, in which excessive consumption of fats and sugars is causing an epidemic of obesity and metabolic disorders,” said first author Mingtong Li, PhD, a postdoctoral researcher in the Charles Zucker Lab of the Zuckerman Institute. Ph.D., supported by the Howard Hughes Medical Institute.
“If we want to control our insatiable craving for fat, the science shows us that the main channel that drives these cravings is the gut-brain connection.”
This new view of healthy food choices began with previous work from the Zucker Lab on sugar. The researchers found that glucose activates a specific brain and gut circuit that communicates with the brain in the presence of intestinal sugar.
By contrast, zero-calorie artificial sweeteners don’t have this effect, and likely explain why diet sodas make us feel so unsatisfied.
Our research shows that the tongue tells our minds what we are Such as“Like things that taste sweet or salty or greasy,” said Dr. Zucker, who is also a professor of biochemistry, molecular biophysics, and neuroscience at Columbia’s Vagelos College of Physicians and Surgeons.
“However, the gut tells our minds what we are WantsWhat do we need?”
Dr. Lee wanted to explore how mice respond to dietary fat: the fats and fatty acids that each animal must consume to provide the building blocks for life. Rats were shown water bottles containing dissolved fats, including a component of soybean oil, and water bottles containing sweet substances that are known to not affect the intestines but are initially attractive.
The rodents developed a strong preference for fatty water over the course of two days. They formed this preference even when scientists genetically modified mice to remove the animals’ ability to taste fat using their tongues.
“Although the animals could not taste fat, they paid to consume it,” Dr. Zucker said.
The researchers argued that fat should activate certain brain circuits that drive the animals’ behavioral response to fat. To research this circuit, Dr. Lee measured the brain activity of mice while the animals were given fat.
Neurons rebound in a specific region of the brainstem, the caudal nucleus of the solitary tract (cNST). This was intriguing because the cNST was also implicated in the pre-laboratory discovery of the neural basis of sugar preference.
Then Dr. Lee found the lines of communication that relayed the message to the cNST. Neurons in the vagus nerve, which connects the gut to the brain, also tweet with activity when mice have fat in their gut.
After determining the biological mechanism underlying a mouse’s preference for fat, Dr. Lee took a closer look at the gut itself: specifically the endothelial cells that line the intestines. She found two groups of cells that send signals to the vagus neurons in response to the fat.
“One group of cells acts as a general sensor for essential nutrients, responding not only to lipids, but also to sugars and amino acids,” said Dr. Lee. “The other group only responds to fats, which may help the brain distinguish fats from other substances in the gut.”
Then Dr. Lee took an important step forward by blocking the activity of these cells with a drug. Turning off signals from any group of cells prevented vagus neurons from responding to fats in the gut. Then, genetic techniques were used to disrupt the vagus neurons themselves, or neurons in the cNST. In both cases, the mouse lost its appetite for fat.
“These interventions demonstrated that each of these biological steps from the gut to the brain is essential to the animal’s response to fat,” said Dr. Lee.
“These experiments also provide new strategies for altering the brain’s response to fats and possibly behavior toward food.”
The stakes are high. Obesity rates worldwide have nearly doubled since 1980. Today, nearly half a billion people suffer from diabetes.
“Excessive consumption of cheap, highly processed foods that are rich in sugar and fat has a devastating impact on human health, especially among low-income and communities of color,” said Dr. Zucker.
“The better we understand how these foods hijack the biological machinery underlying taste and the gut axis, the more opportunity we have to intervene.”
Scott Sternson, PhD, professor of neuroscience at the University of California, San Diego, who was not involved in the new research, highlighted its potential to improve human health.
“This exciting study provides insight into the molecules and cells that compel animals to crave fat,” said Dr. Sternson, whose work focuses on how the brain controls appetite.
“Researchers’ ability to control this craving may eventually lead to treatments that may help combat obesity by reducing consumption of fatty, high-calorie foods.”
About this research in neuroscience and the gut axis
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“Gut and brain circuits for fat preferenceFrom Mengtong Li, Hwei-Ee Tan, Zhengyuan Lu, Katherine S. Tsang, Ashley J. Chung, and Charles S. Zuker. temper nature
Gut and brain circuits for fat preference
The perception of fat elicits powerful, appetizing responses. Here we show that fatty stimuli can induce behavioral attraction even in the absence of a functional taste system. We demonstrated that post-ingestion lipids act across the gut-brain axis to stimulate preference for lipids.
Using single-cell data, we identified vagal neurons that respond to lipid delivery in the gut, and showed that genetic silencing of this gut-to-brain circuit abolished the development of fat preference.
Next, we compared the gut-brain pathways that drive the preference for fat versus sugar, and discovered two parallel systems, one of which acts as a general sensor for essential nutrients, responding to gut stimulation with sugar, fat, and amino acids, while the other is activated only by fatty stimuli.
Finally, we designed animals lacking candidate receptors that detect the presence of intestinal fat, and investigated their role as mediators of brain fat-evoked responses.
Together, these results revealed distinct cells and receptors that use the gut-brain axis as an essential channel for the development of lipid preference.