(CNN) — Obesity may damage the brain’s ability to recognize the sensation of fullness and be satisfied after eating fats and sugars, a new study found.

Further, those brain changes may last even after people considered medically obese lose a significant amount of weight — possibly explaining why many people often regain the pounds they lose.

“There was no sign of reversibility — the brains of people with obesity continued to lack the chemical responses that tell the body, ‘OK, you ate enough,’” said Dr. Caroline Apovian, a professor of medicine at Harvard Medical School and codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital in Boston.

As defined medically, people with obesity have a body mass index, or BMI, of over 30, while normal weight is a BMI of between 18 and 25.

“This study captures why obesity is a disease — there are actual changes to the brain,” said Apovian, who was not involved in the study.

“The study is very rigorous and quite comprehensive,” said Dr. I. Sadaf Farooqi, a professor of metabolism and medicine at the University of Cambridge in the UK, who was not involved in the new research.

“The way they’ve designed their study gives more confidence in the findings, adding to prior research that also found obesity causes some changes in the brain,” she said.

Nutrients delivered by feeding tube

The study, published Monday in Nature Metabolism, was a controlled clinical trial in which 30 people considered to be medically obese and 30 people of normal weight were fed sugar carbohydrates (glucose), fats (lipids) or water (as a control). Each group of nutrients were fed directly into the stomach via a feeding tube on separate days.

“We wanted to bypass the mouth and focus on the gut-brain connection, to see how nutrients affect the brain independently from seeing, smelling or tasting food,” said lead study author Dr. Mireille Serlie, professor of endocrinology at Yale School of Medicine in New Haven, Connecticut.

The night before the testing, all 60 study participants had the same meal for dinner at home and did not eat again until the feeding tube was in place the next morning. As either sugars or fats entered the stomach via the tube, researchers used functional magnetic resonance imaging (fMRI) and single-photon emission computed tomography (SPECT) to capture the brain’s response over 30 minutes.

“The MRI shows where neurons in the brain are using oxygen in reaction to the nutrient — that part of the brain lights up,” Farooqi said. “The other scan measures dopamine, a hormone that is part of the reward system, which is a signal for finding something pleasurable, rewarding and motivating and then wanting that thing.”

Researchers were interested in how fats and glucose would individually trigger various areas of the brain connected to the rewarding aspects of food. They wanted to know if that would be different in people with obesity compared to those of normal weight.

“We were especially interested in the striatum, the part of the brain involved in the motivation to actually go and look for food and eat it,” Serlie said. Buried deep in the brain, the striatum also plays a role in emotion and habit formation.

In people with normal weight, the study found brain signals in the striatum slowed when either sugars or fats were put into the digestive system — evidence that the brain recognized the body had been fed.

“This overall reduction in brain activity makes sense because once food is in your stomach, you don’t need to go and get more food,” Serlie explained.

At the same time, levels of dopamine rose in those at normal weight, signaling that the reward centers of the brain were also activated.

Different findings for medically obese

However, when the same nutrients were given via feeding tube to people considered medically obese, brain activity did not slow, and dopamine levels did not rise.

This was especially true when the food was lipids or fats. That finding was interesting, Farooqi said, because the higher the fat content, the more rewarding the food: “That’s why you will genuinely want a burger instead of broccoli, the fat in the burger will biologically give a better response in the brain.”

Next, the study asked people with obesity to lose 10% of their body weight within three months — an amount of weight known to improve blood sugars, reset metabolism and boost overall health, Serlie said.

Tests were repeated as before — with surprising results. Losing weight did not reset the brain in people with obesity, Serlie said.

“Nothing changed — the brain still did not recognize fullness or feel satisfied,” she said. “Now, you might say three months is not long enough, or they didn’t lose enough weight.

“But this finding might also explain why people lose weight successfully and then regain all the weight a few years later — the impact on the brain may not be as reversible as we would like it to be.”

A 2018 meta-analysis of long-term weight loss clinical trials found 50% of a person’s original weight loss was regained after two years — by the fifth year, 80% of the weight was regained.

More research needed

Caution is needed in interpreting the findings, Serlie said, as much is unknown: “We don’t know when these profound changes in the brain happen during the course of weight gain. When does the brain start to slip and lose the sensing capacity?”

Obesity has a genetic component, and although the study attempted to control for that by excluding people with childhood onset obesity, it’s still possible that “genes are influencing our response in the brain to certain nutrients,” said Farooqi, who has studied the role of genes on weight for years.

Much more research is needed to fully understand what obesity does to the brain, and if that is triggered by the fat tissue itself, the types of food eaten, or other environmental and genetic factors.

“Are there changes that occurred in people as they gained weight? Or are there things that they were eating as they were gaining weight, such as ultra-processed foods, that caused a change in the brain? All of these are possible, and we don’t really know which it is,” Farooqi said.

Until science answers these questions, the study emphasizes, once again, that weight stigma has no place in the fight against obesity, Serlie said.

“The belief that weight gain can be solved simply by ‘just eating less, exercising more, and if you don’t do that, it’s a lack of willpower is so simplistic and so untrue,” she said.

“I think it’s important for people who are struggling with obesity to know that a malfunctioning brain may be the reason they wrestle with food intake,” Serlie said. “And hopefully this information will increase empathy for that struggle.”

Obesity changes the brain, with ‘no sign of reversibility,’ expert says