A study shows how brain responses to nutrients are severely impaired in people with obesity and Indian doctors are agreeing with it.
People with obesity have impaired brain responses to nutrients in the gut and this impairment persists even after weight loss through dietary changes. (Creatives Commons)
Imagine this: You sit down to a mouthwatering feast, devouring a greasy plate full of delicious fats and sugars. As you take each bite, your brain sends a signal to your body after a point, saying, “All right, you’ve had enough, time to stop.”
But a new study has found that, for individuals grappling with obesity, that crucial message may be lost in translation.
There is a concerning link between obesity and the brain’s ability to recognise fullness and satisfaction after indulging in fatty and sugary foods. When understood, scientists believe this phenomenon may help strategise different methods to regulate eating behaviour.
Researchers from Amsterdam University Medical Center and Yale University found that while the detection of nutrients in the stomach does induce brain activity changes in people with lean bodies, such brain responses are largely diminished in people with obesity.
Obesity creates a communication gap between the brain and the gut, leading to a cycle of overeating. The study published in Nature Metabolism sheds light on the complex relationship between the two and highlights the challenges faced by individuals with obesity.
Obesity impairs the brain’s responses to nutrients in the gut and this impairment persists even after weight loss through dietary changes. The research utilised brain imaging techniques to observe how the brain of individuals with and without obesity react to nutrients.
Representational image of boy eating junk food leading to obesity. (Wikimedia Commons)
The results demonstrated that when individuals without obesity received nutrients, their brain activity in food intake-related areas decreased, indicating that the brain signals satiety and the absence of further food requirements. However, these changes were not observed in individuals with obesity.
This study adds to the growing body of research that highlights the intricate and persistent biological effects of obesity, dispelling the notion that it is solely a result of personal willpower. These differences in brain activity, the researchers said, could help explain why it’s difficult for some to lose weight and maintain the weight loss.
Mireille Serlie, senior author and a professor of medicine at Yale University, emphasised in the study that obesity is more than a lack of willpower. She explained that individuals with obesity experience a mismatch between the sensing of food in the body and the brain’s response to it, indicating an ongoing biological process that contributes to the struggle with obesity and weight maintenance.
According to the researchers, over four million people die each year around the world as a result of being overweight (according to the World Health Organisation) and understanding the biological factors that contribute to obesity will be essential to address its devastating, global impact.
And while the ways that the body responds to nutrient intake may be a key factor in eating behaviour, the role of nutrient signalling in humans is not well understood.
Individuals are considered medically obese if their Body Mass Index (BMI) exceeds 30, while a BMI between 18 and 25 falls within the normal range — known simply as lean. For the new study, researchers infused glucose or fat directly into the stomach of 28 people identified as “lean” and 30 people with obesity. They then assessed brain activity though a functional MRI (fMRI).
In an attempt to shed light on the issue, the study asked people with obesity to reduce their body weight by 10 percent within three months — an amount known to improve blood sugar levels, reset metabolism, and enhance overall health.
Surprisingly, weight loss failed to reset the brain’s functioning in individuals with obesity. However, among the lean participants, the researchers saw evidence of reduced activity across various regions of the brain following the infusion of both glucose and fat.
“This was surprising,” said Serlie and added, “We knew there would be different responses between lean people and people with obesity, but we didn’t expect lack of changes in brain activity in people with obesity.”
Serlie and her colleagues then took a closer look at a brain region called the striatum, which previous research has shown to mediate the rewarding and motivational aspects of food intake and plays a key role in regulating eating behaviour.
The striatum does this in part through the neurotransmitter dopamine. Using fMRI, they found that in lean people, both glucose and fat led to decreased activity in two parts of the striatum. However, only glucose led to changes in brain activity in participants with obesity and only in one area of the striatum. Fat did not change brain activity in this region.
When researchers evaluated dopamine release in the striatum following nutrient infusion, they found that glucose-induced dopamine release in both groups of participants, while fat only caused dopamine release in lean participants.
Representative image. (Wikimedia Commons)
These findings, the researchers said, are compatible with reduced nutrient sensing in people with obesity. For the study, participants with obesity then underwent a 12-week dietary weight-loss programme. Those who lost at least 10 percent of their body weight were then re-imaged.
But here’s the kicker: Even when participants managed to lose 10 percent of their body weight over a span of three months, losing weight did not magically reset the brain’s malfunctioning signals of fullness and satisfaction. The brain remained stubborn, failing to acknowledge the progress made.
Dr Serile noted, “Nothing changed. The brain still did not reconsider fullness or feel satisfied. None of the diminished responses were recovered.” Prior analyses have found that most people who lose weight, regain it within a few years of dieting.
These new findings, the researchers said, may help explain why that’s so often the case. “In my clinic, when I see people with obesity, they often tell me, ‘I ate dinner. I know I did. But it doesn’t feel like it’,” said Serlie.
“And I think that’s part of this defective nutrient sensing. This may be why people overeat, despite the fact that they’ve consumed enough calories. And, importantly, it might explain why it’s so hard to keep the weight off.”
Understanding the biology of eating behaviour in humans is still in its early stages, said Serlie, and more research will be needed to uncover why diminished nutrient sensing occurs in some people, what biological pathways are involved, and when these changes begin to take hold.
“Everyone overeats at times. But it’s unclear why some people continue to overeat and others don’t,” she said. “We need to find where that point is when the brain starts to lose its capacity to regulate food intake and what determines that switch. Because if you know when and how it happens, you might be able to prevent it,” she explained.
Similarly, knowing when changes to nutrient sensing become irreversible would help physicians determine treatment paths for patients. And one goal for the future, Serlie said, would be to find a way to restore nutrient sensing, if possible. Regardless, the findings uncover the human brain’s key role in obesity.
“People still think obesity is caused by a lack of willpower,” said Serlie, “But we’ve shown that there is a real difference in the brain when it comes to nutrient sensing.”
At a time when India, especially South Indian states, are grappling with obesity, the study throws light on brain connections.
However, Dr Sudhir Kumar, Consultant Neurologist at Apollo Hospitals in Hyderabad said that food intake is regulated by various factors that directly or indirectly affect hunger or satiety. These include habit, which means eating food on time whether one is hungry or not.
He said that smell and taste (palatability) has a great bearing on food intake.
“It would need strong willpower to skip having rabdi, jalebi or rasgulla for sweet lovers. On the other hand, when food is not tasty, one can easily avoid having it. However, the most important mechanisms of regulating hunger and satiety are based in the brain,” he said.
The two hormones most closely associated with energy homeostasis, leading to sensations of hunger, are ghrelin and leptin. Levels of ghrelin increase before meals and has a role in increasing body weight, thus earning the name “hunger hormone”.
The lateral area of the hypothalamus is responsible for hunger and becomes stimulated by ghrelin.
“Leptin is best understood as the opposite of ghrelin, acting as the body’s satiety signal. The ventromedial region of the hypothalamus is responsible for satiety and is stimulated by leptin. The responses to food intake differ between people with lean body weight from those who are obese (or overweight). In a person with lean (or normal) body weight, after intake of food rich in glucose or fats, there is a release of dopamine from the striatum and there is a feeling of satiety,” elaborated Dr Sudhir.
Doctors said that on the other hand, among obese people, the reward centre is not activated even after food intake, which makes them consume food beyond what is needed for energy homeostasis. Another interesting observation in this study, according to Dr Sudhir, is that even after achieving weight loss, the brain response remained affected.
This can explain the regaining of lost weight over time in obese or overweight individuals. These are interesting observations, “however, long-term studies are needed to confirm these observations (this was a short-term study). The mechanisms involved in this dysfunction also need to be studied,” suggested Dr Sudhir.
Meanwhile, Dr Mahesh Gowda, Consultant Psychiatrist and Chairman at Spandana Group of Hospitals, also spoke about the hormones leptin and ghrelin.
He said, “There is a good negative feedback mechanism in our bodies that is induced by leptin to control the feeding behaviour, but people with obesity have a problem with eating as their appetite centre is over stimulated and leptin doesn’t work.”
Interestingly, Dr Gowda said that, to a certain extent, eating slowly helps people with obesity in tricking their brain or convincing it that their stomach is full and don’t need to eat more.
“The way they eat also matters. People who tend to eat very fast tend to put on weight. Whereas people who are mindful eaters and eat very slowly reach satisfaction much faster and eating behaviour will come down.”
May 11, 2024
May 11, 2024
May 10, 2024
May 10, 2024
May 09, 2024
May 09, 2024
