Study details

For the study, researchers took 30 patients considered to be medically obese and 30 patients considered to have a normal weight and fed them sugar, fats, and water directly into the stomach through a feeding tube.

According to Mireille Serlie, professor of endocrinology at Yale School of Medicine and lead author on the study, the feeding tube was used in an effort "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."

The night before the testing began, all study participants ate the same meal for dinner and didn't eat again until the feeding tube was in place the next day. As sugars or fats entered the stomach, researchers used functional magnetic resonance imaging and single-photon emission computed tomography to monitor the brain's response over the course of 30 minutes.

Researchers were specifically interested in how areas of the brain connected to the rewarding aspects of food were affected by fats and glucose, and whether these responses would be different in obese patients.

"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.

In normal weight patients, the researchers found that when sugars or fats were put into the digestive system, brain signals in the striatum slowed, meaning the brain recognized the body had been fed. At the same time, dopamine levels rose signaling the reward centers in the brain were activated. In obese patients, however, the researchers found that brain activity didn't slow when patients were given the same nutrients, and dopamine levels didn't rise, especially when the food was lipids or fats.

The researchers then asked the patients with obesity to lose 10% of their body weight within three months. According to Serlie, losing 10% of body weight is known to improve a person's blood sugars, reset their metabolism, and improve their overall health.

After the patients with obesity lost weight, the researchers performed the same tests again and found that losing weight didn't reset the brain in those patients.

"Nothing changed — the brain still did not recognize fullness or feel satisfied," Serlie said.

Discussion

"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 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.

According to Serlie, the finding that losing weight doesn't change how the brain is affected by nutrients "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."

Serlie cautioned that much is still unknown and that more research is needed. "We don't know when these profound changes in the brain happen during the course of weight gain," she said. "When does the brain start to slip and lose the sensing capacity?"

I. Sadaf Farooqi, a professor of metabolism and medicine at the University of Cambridge who was not involved in the study, said, "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." However, Farooqi added that more research is needed to fully understand how obesity affects the brain.

"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?" Farooqi said. "All of these are possible, and we don't really know which it is."

Obesity also has a genetic component, and while the study tried to control for that by excluding patients with childhood onset obesity, it's possible that "genes are influencing our response in the brain to certain nutrients," Farooqi said.

Serlie noted the study adds to the literature proving obesity is "not just simply a lack of willpower."

"The sensing of food being present in the body and the brain's reaction to it is not in alignment in people with obesity," she said. "There's a biological process ongoing that really explains why people are struggling so much with obesity" and why it's hard to keep weight off.

Paul Kenny, chair of the department of neuroscience at the Icahn School of Medicine at Mount Sinai, who also researches the neurobiological mechanisms of obesity, said "all too often, people think that if you're overweight, it's really simple, just stop eating and you lose weight — problem solved. Papers like this get to the fact that it's not so easy."

"When you consume certain foods that result in weight gain, that can actually remodel the brain and how the brain works and those changes can be very long-lasting," Kenny added. "And those long-lasting changes presumably are influencing your choices regarding food in the future." (LaMotte, CNN, 6/12; Chen, STAT, 6/12)

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