It’s pretty well-known that weight loss ranks high among common exercise goals, especially at the start of the year. But if trimming that belly fat is on your list, and you assume that exercise is the magic solution, it might be time to reconsider.
“Exercising is crucial for overall health, impacting nearly every measurable disease – but it’s not the answer for weight loss,” states Professor Christoffer Clemmensen from the University of Copenhagen’s Novo Nordisk Foundation Centre for Basic Metabolic Research.
Research has consistently shown that the old saying “eat less; move more” doesn’t actually work for those trying to shed body fat. And the notion that willpower is key? Well, that’s also misleading.
“Weight loss isn’t just about willpower,” adds PhD candidate Valdemar Brimnes Ingemann Johansen, his collaborator. “It’s important to recognize the strong biological forces at play that influence our behavior.”
“Genetics play a significant role in determining our body shape and size, and often, this biology is beyond an individual’s control.”
Their recent literature review, featured in the Cell journal, explores lesser-known factors influencing weight loss, which could be beneficial as you aim to meet your goals this year.
The issue with calorie deficit
A calorie is commonly understood as a unit of energy. More precisely, a kilocalorie is the energy required to raise 1kg of water by 1°C. For centuries, this has served as a standard for conveying energy content in food and drinks.
A calorie deficit is often touted as the key to weight loss, suggesting that if you burn more calories than you consume, you’ll lose weight. Experts agree with this principle.
“People can lose weight in restrictive conditions,” says Professor Clemmensen. “The laws of thermodynamics hold; if there’s a negative energy balance, you will lose weight.
“But you can’t expect people to maintain that balance in their daily lives because strong biological impulses drive them to eat. Without controlling portion sizes or locking away food, it’s nearly impossible.”
“These comments about calorie deficits overlook the biological mechanisms behind weight regulation. It’s akin to advising stressed individuals to just relax, or telling someone with mental health issues to simply get it together.”
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The new science of weight loss
Obesity is categorized as a chronic condition by the World Health Organization, with data indicating that in 2021, excessive BMI contributed to approximately 3.7 million deaths due to noncommunicable diseases like heart disease, diabetes, cancer, neurological and respiratory issues.
So, why do our bodies appear to have built-in mechanisms favoring a condition linked to poor health? According to Johansen, it may have roots in our evolutionary history.
For our ancestors, stored fat served as a buffer against starvation during food shortages, so our bodies tend to “remember” that and seek to restore these reserves when food becomes available. This can make weight loss seem like a threat, inspiring the body to ramp up hunger signals while simultaneously lowering our energy output.
In the past, this might have been beneficial; today, with energy-dense foods easily accessible and less physical activity required, these instincts can actually hinder progress.
Professor Clemmensen conducted a literature review in 2025 highlighting what he calls an “obesity memory.”
“This memory of obesity might be complex,” he explains. “We aren’t clear on where it manifests, but the evidence suggests it’s present. Studies show most individuals undergoing significant weight loss tend to revert to their initial weight.
“It appears there’s a distinct memory regarding one’s weight. Understanding this is a focus in our laboratory.”
This memory isn’t uniform and likely varies widely based on genetics.
“The capacity for someone to maintain weight loss and respond to various interventions—both behavioral and pharmacological—depends on the individual,” Johansen remarks. “There’s notable variability observed in large clinical trials.”
“It would be fascinating to discern why some individuals regain weight shortly after losing it while others maintain their weight loss for extended periods. I suspect it relates to how their environment interacts with their genetic profile.”
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What actually supports weight loss?
Anyone who’s attempted to lose weight knows there’s often a gap between the desire to lose body fat and actually achieving it. Professor Clemmensen’s concept of “obesity memory” could shed some light on this.
But if the mantra of “eat less; move more” doesn’t yield results, what does? This is a challenging question, as ongoing research continues to explore the issue.
“Do we truly possess enough knowledge to steer individuals on how to live in order to lose weight? I’m inclined to say no. That’s a hard reality we researchers must face,” he says.
This doesn’t imply that diet and exercise lack importance—healthy behaviors should always be prioritized. Consuming a balanced diet filled with a variety of vegetables and protein, along with some fish, is more likely to positively impact your body composition and overall health than opting for less nutrient-rich options like junk food.
“Different macronutrient compositions yield varying effects on hormonal systems,” Professor Clemmensen explains. “Consuming calories from liquid sugar versus chicken breast leads to markedly different hormonal responses and sensations of hunger.”
The same logic applies to exercise. While being more active can greatly improve health indicators like blood pressure and decrease chronic disease risk, Professor Clemmensen notes, “There’s scant evidence indicating it can counter the memory of previous body weight.”
No single method seems to offer a complete solution, and people’s unique genetic traits mean there’s no one-size-fits-all approach. However, a blend of manageable lifestyle changes seems to hold the most promise.
Establishing sustainable habits—adequate sleep, a nutritious diet, and regular exercise—can significantly enhance overall health. These can also potentially aid in regulating appetite, maintaining energy balance, and managing weight.
Yet, both Professor Clemmensen and Johansen suggest that broader societal changes, long-term strategies, and medical interventions are essential to curb obesity rates over time.
The obesity solution
“Addressing obesity calls for a long-term view, considering generations beyond our immediate context,” states Professor Clemmensen. “We need to invest considerable research into preventive strategies that create environments that minimize unhealthy gene-environment interactions.”
In simpler terms, societal changes should encourage healthier habits—boosting the presence of nutritious foods over heavily processed, high-calorie options, and designing neighborhoods that favor walking and biking instead of driving.
And what about weight loss medications like Ozempic, Wegovy, and Mounjaro, classified as “pharmacological interventions”?
“These drugs have really highlighted to individuals how tough maintaining weight loss through sheer willpower can be,” remarks Professor Clemmensen. “Now we have effective pharmacological options available for those struggling with health issues caused by excess body fat.”
However, Johansen cautions that many weight loss medications “don’t seem effective for sustaining weight loss once treatment stops.”
“Patients often deal with returning health issues such as diabetes, high blood pressure, and systemic inflammation after ending treatment,” he adds.
“Some evidence indicates that combining exercise and pharmacological approaches can be beneficial for maintaining weight loss.”
Professor Clemmensen also highlights the need to foster healthy habits in children, particularly those under seven, as they have a more adaptable weight regulation system.
“Critical periods in life exist—during gestation, after birth, and between ages four and seven, and again during adolescence,” he notes.
“Genetics may influence weight changes, but creating a conducive environment is essential during these key stages to prevent excess fat accumulation.
“Instead of restricting children, we should ensure they don’t have unlimited access to high-calorie foods around the clock, while also minimizing screen time, poor sleep, and psychological issues.”
This could involve limiting junk food advertising to children, improving the quality of school meals, standardizing restaurant portion sizes, and promoting regular physical activity.
Fostering positive behaviors in childhood that align with one’s genetic predisposition might promote less body fat in adulthood, Professor Clemmensen suggests.
Ultimately, he believes that the most promising avenue for success lies in researching, identifying, and modifying one’s “obesity memory.”
“If we can discover where and how this memory is formed, possibly we could erase it and help people reset their weight,” he indicates. “By better understanding physiology, we could learn how to intervene effectively.”
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