Craving donuts? Scientists discover urge for junk food comes from gut signal to brain

A gut-brain signal that gives people the urge to gorge on junk food has been discovered by scientists. It fuels cravings for fatty foods, offering hope of new treatments for obesity and binge eating.

The delicious taste of burgers, pizza, and ice cream can be tough to resist for some, but turning off this newfound circuit may hold the key. It connects fat sensors in the gut with neurons in gray matter. A signal is carried along nerves, driving our desire for unhealthy foods.

“We live in unprecedented times, in which the overconsumption of fats and sugars is causing an epidemic of obesity and metabolic disorders,” says first author Dr. Mengtong Li, a postdoctoral researcher at Columbia University, in a statement. “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.”

The study raises the possibility of breaking the link combating the growing global health crisis caused by overeating. It builds on the team’s previous work on sugar. They found a similar reaction in response to intestinal sugar. Calorie-free artificial sweeteners, on the other hand, did not have the same effect, shedding light on why diet drinks can leave us feeling unsatisfied.

“Our research is showing the tongue tells our brain what we like, such as things that taste sweet, salty or fatty,” says co-author Dr. Charles Zuker, 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.”

In experiments, Dr. Li offered mice bottles of water laced with dissolved fats — either components of soybean oil or tasty sweet substances known to not affect the gut. Over a couple of days the lab rodents developed a strong preference for the formula, even those genetically modified so they could not taste fat with their tongue.

“Even though the animals could not taste fat, they were nevertheless driven to consume it,” says Zuker.

Vagal neurons that carry signals from the gut to the brain
Vagal neurons that carry signals from the gut to the brain (nuclei shown in blue), with cells responsible for fat preference in green. (Credit: Mengtong Li / Zuker lab / Columbia’s Zuckerman Institute)

The researchers reasoned behavioral responses to fat were being triggered by specific brain circuits. Scans showed neurons in one particular region of the brainstem, the cNST (caudal nucleus of the solitary tract), perked up.

It was also implicated in the earlier discovery relating to sugar preference. Dr Li then found communication lines that carried the message. Neurons in the vagus nerve, which links the gut to the brain, also twittered with activity when mice had fat in their intestines.

She next took a close look at the gut itself, specifically the endothelial cells lining the intestines. Two groups of cells sent signals to the vagal neurons in response to fat.

“One group of cells functions as a general sensor of essential nutrients, responding not only to fat, but also to sugars and amino acids,” explains Li. “The other group responds to only fat, potentially helping the brain distinguish fats from other substances in the gut.”

She then went a step further by blocking the cells using a drug. Shutting down signaling from either group prevented vagal neurons from responding to fat in the intestines. Genetic techniques to deactivate either the vagal neurons themselves or the neurons in the cNST had the same affect. In both cases, a mouse lost its appetite for fat.

“These interventions verified that each of these biological steps from the gut to the brain is critical for an animal’s response to fat,” says Li. “These experiments also provide novel strategies for changing the brain’s response to fat and possibly behavior toward food.”

The stakes are high. Obesity rates have nearly doubled worldwide since 1980. Today, nearly half a billion people suffer from diabetes.

“The overconsumption of cheap, highly processed foods rich in sugar and fat is having a devastating impact on human health, especially among people of low income and in communities of color,” notes Zuker. “The better we understand how these foods hijack the biological machinery underlying taste and the gut-brain axis, the more opportunity we will have to intervene.”

The study is published in the journal Nature.

Report by Mark Waghorn, South West News Service

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