Cravings for fatty foods traced to gut-brain connection

A dieter who struggles with cravings for fatty foods could be inclined to put the blame on their tongue because it can be difficult to resist the delightful flavor of butter or ice cream. However, brand-new studies looking into what makes us hungry have found a brand-new link between the gut and the brain that fuels our appetite for fat.

Fat entering the intestines causes a signal to be triggered, according to research conducted on mice at Columbia University's Zuckerman Institute. Conducted along nerves to the brain, this signal generates a desire for fatty meals. The new research, which will be published in Nature on September 7, 2022, suggests that it may be possible to interfere with this gut-brain connection in order to avoid bad decisions and solve the escalating worldwide health crisis brought on by overeating.

"We live in unusual times," stated first author Mengtong Li, PhD, a postdoctoral researcher in Charles Zuker's lab at the Zuckerman Institute who was funded by the Howard Hughes Medical Institute. "Overconsumption of fats and carbohydrates is producing an epidemic of obesity and metabolic problems." Science is teaching us that the connection between the gut and the brain is the main mechanism behind our compulsive appetite for fat, and that if we want to regulate it, we must do so.

Prior research on sugar from the Zuker lab served as the foundation for this new perspective on dietary choices and health. Researchers discovered that in the presence of intestinal sugar, glucose triggers a particular gut-brain circuit that communicates with the brain. Contrarily, calorie-free artificial sweeteners do not have this impact, which perhaps explains why diet sodas often make us feel unfulfilled.

According to Dr. Zuker, who is also a professor of biochemistry and molecular biophysics and of neuroscience at Columbia's Vagelos College of Physicians and Surgeons, "our research shows that the tongue communicates our brain what we prefer, such as things that taste sweet, salty, or fatty." The gut, however, communicates to the brain what we need and want.

Dr. Li was interested in learning how mice reacted to dietary fats, which all animals must ingest to obtain the essential nutrients for survival. She gave mice bottles of water containing dissolved lipids, including a soy oil component, and bottles of water containing sweet compounds that are initially alluring but are known not to damage the gut. Over the course of a few days, the rats grew fond to the fatty water. Even after the researchers genetically altered the mice to prevent them from using their tongues to taste fat, they developed this predilection.

The animals were compelled to eat the fat even though they couldn't taste it, according to Dr. Zuker.

According to the researchers, fat must be engaging particular brain circuits that are responsible for the animals' behavioral response to fat. Dr. Li examined brain activity in mice while feeding them fat in an effort to identify that circuit. The caudal nucleus of the solitary tract (cNST), a specific area of the brainstem, had an uptick in its population of neurons. This was intriguing because the lab's earlier discovery of the neurological basis of sugar desire also involved the cNST.

The communication channels that sent the message to the cNST were then discovered by Dr. Li. When mice had fat in their intestines, the vagus nerve, which connects the gut to the brain, also twittered with activity.

Dr. Li first examined the molecular mechanisms underpinning a mouse's desire for fat before focusing on the endothelial cells that line the intestines. She found two sets of cells that delivered signals to the vagal neurons in response to fat.

Dr. Li explained that one set of cells serves as a general sensor of important nutrients, reacting to carbohydrates, amino acids, and fats in addition to fat itself. The other group solely reacts to fat, possibly assisting the brain in differentiating between lipids and other chemicals in the gut.

Dr. Li then took a crucial step further by utilizing a medication to stop the activity of these cells. When each cell group's signaling was turned off, vagal neurons were unable to react to dietary fat in the intestines. After that, she used genetic methods to either silence the vagal neurons directly or the neurons in the cNST. A mouse lost its appetite for fat in both situations.

The biochemical processes from the gut to the brain are all essential for an animal's reaction to fat, according to Dr. Li's treatments. These studies offer innovative methods for altering the brain's reaction to fat and perhaps eating behavior.

The odds are against us. Since 1980, the prevalence of obesity has nearly doubled worldwide. Nearly half a billion individuals worldwide have diabetes today.

Especially among low-income individuals and members of communities of color, "overconsumption of inexpensive, highly processed foods rich in sugar and fat is having a terrible influence on human health," claimed Dr. Zuker. "The more opportunities we have to intervene, the better we will understand how these foods hijack the cellular machinery driving taste and the gut-brain axis."

The new study has the potential to improve human health, according to Scott Sternson, PhD, a professor of neurology at the University of California, San Diego. Sternson was not involved in the current study.

Dr. Sternson, whose research focuses on how the brain regulates hunger, noted that this fascinating discovery "provides understanding about the chemicals and cells that push animals to crave fat." Researchers' ability to manage this desire may someday result in therapies that could help fight obesity by lowering consumption of high-calorie, fatty meals.

The Russell Berrie Foundation's program on the neuroscience of obesity helped fund some of this study. Investigator Charles Zuker works with the Howard Hughes Medical Institute.

Columbia University