Cravings for fatty foods traced to gut-brain connection: Mouse research reveals fat sensors in the intestines that stimulate the brain and drive food desires

A dieter wrestling 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 investigating the source of our appetites has uncovered an entirely new connection between the gut and the brain that drives our desire for fat.

At Columbia’s Zuckerman Institute, scientists studying mice found that fat entering the intestines triggers a signal. Conducted along nerves to the brain, this signal drives a desire for fatty foods. Published September 7, 2022, in Nature, the new study raises the possibility of interfering with this gut-brain connection to help prevent unhealthy choices and address the growing global health crisis caused by overeating.

“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, PhD, a postdoctoral researcher in the lab of the Zuckerman Institute’s Charles Zuker, PhD, supported by the Howard Hughes Medical Institute. “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.”

This new view of dietary choices and health started with previous work from the Zuker lab on sugar. Researchers found that glucose activates a specific gut-brain circuit that communicates to the brain in the presence of intestinal sugar. Calorie-free artificial sweeteners, in contrast, do not have this effect, likely explaining why diet sodas can leave us feeling unsatisfied.

“Our research is showing that the tongue tells our brain what we like, such as things that taste sweet, salty or fatty,” said Dr. Zuker, who is also a professor of biochemistry and molecular biophysics and of neuroscience at Columbia’s Vagelos College of Physicians and Surgeons. “The gut, however, tells our brain what we want, what we need.”

Dr. Li wanted to explore how mice respond to dietary fats: the lipids and fatty acids that every animal must consume to provide the building blocks of life. She offered mice bottles of water with dissolved fats, including a component of soybean oil, and bottles of water containing sweet substances known to not affect the gut but that are initially attractive. The rodents developed a strong preference, over a couple of days, for the fatty water. They formed this preference even when the scientists genetically modified the mice to remove the animals’ ability to taste fat using their tongues.

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