A dieter who struggles with cravings for fatty foods might be tempted to put the blame on their tongue because it can be difficult to resist the delicious taste 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. According to research conducted on mice at Columbia University‘s Zuckerman Institute, fat entering the intestines causes a signal to be triggered. This signal triggers a craving for fatty foods when it travels along nerves to the brain. The new research, which will be published in Nature on September 7, 2022, suggests that it might be possible to mess with the connection between the gut-brain to stop people from making bad decisions and help solve the growing health crisis caused by overeating around the world.
“We live in unprecedented times,” said 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 sugars is causing an epidemic of obesity and metabolic disorders.” Science is showing us that the connection the gut-brain is the main mechanism causing our compulsive craving for fat, and that if we want to control 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 activates a particular gut-brain circuit that communicates with the brain. Artificial sweeteners without calories, on the other hand, don’t have this effect. This is probably why diet sodas sometimes leave us feeling hungry.
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 tells our brain what we like, 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 consume to obtain the essential nutrients for life. She gave mice bottles of water containing dissolved fats, including a soy oil component, and bottles of water containing sweet substances that are initially alluring but are known not to affect the gut. Over the course of a few days, the rodents grew fond of the fatty water. Even after the scientists changed the mice’s genes to stop them from using their tongues to taste fat, they still liked it.
According to Dr. Zuker, the animals were compelled to eat the fat even though they couldn’t taste it.
According to the researchers, fat must be activating particular brain circuits that are responsible for the animals’ behavioral responses to fat. Dr. Li measured 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, experienced an uptick in its population of neurons. This was interesting because the lab had already found that the cNST was involved in the neural basis of sugar preference.
The communication channels that delivered 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 biological mechanisms underlying a mouse’s preference for fat before focusing on the endothelial cells that line the intestines. She discovered two sets of cells that responded to fat by signaling the vagal neurons.
Dr. Li explained that one set of cells serves as a general sensor of essential nutrients, reacting to sugars, amino acids, and fats in addition to fat itself. The other group of cells only reacts to fat, which could help the brain tell the difference between fats and other things in the gut.
Dr. Li then took an important step further by using a drug to block the activity of these cells. When either 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 deactivate the vagal neurons directly or the neurons in the cNST. A mouse lost its appetite for fat in both situations.
The biological processes from the gut to the brain are all essential for an animal’s reaction to fat, according to Dr. Li’s interventions. These studies show new ways to change how the brain reacts to fat and maybe even how people eat.
The odds are against us. Since 1980, the prevalence of obesity has nearly doubled worldwide. Nearly half a billion people worldwide have diabetes today.
Especially among low-income individuals and members of communities of color, “overconsumption of cheap, highly processed foods rich in sugar and fat is having a devastating impact on human health,” claimed Dr. Zuker. “The more chances we have to help, the better we will understand how these foods take over the biological systems that make taste and the gut-brain axis work.”
The new study has the potential to improve human health, according to Scott Sternson, PhD, a professor of neuroscience at the University of California, San Diego. Sternson was not involved in the new study.
Dr. Sternson, whose research focuses on how the brain regulates appetite, said that this fascinating study “offers insight about the molecules and cells that compel animals to desire fat.” Researchers’ ability to manage this desire may eventually result in therapies that could help fight obesity by reducing consumption of high-calorie, fatty foods.
The study, “Gut-Brain Circuits for Fat Preference,” appeared in Nature on September 7, 2022. Authors include Mengtong Li, Charles S. Zuker, Hwei-Ee Tan, Zhengyuan Lu, Katherine S. Tsang, Ashley J. Chung, and others.
The Russell Berrie Foundation’s program on the neurobiology of obesity helped fund some of this study. Investigator Charles Zuker works for the Howard Hughes Medical Institute.
Conflicts of interest: Charles Zuker is also a scientific cofounder and advisor for Kallyope, a biotech company that is building a therapeutic platform. This is based on our deep knowledge of how the gut-brain work together.
