Scientists Identify the Biological Memory That Makes Obesity Relapse So Hard to Prevent
Key Takeaways:
- Researchers have identified a lasting biological change in fat cells – an “obesity memory” – that keeps the appetite-stimulating hormone asprosin elevated even after a person or animal has lost the excess weight.
- The same inflammatory signal can cross the placenta, programming a baby’s fat cells before birth and offering a molecular explanation for why obesity risk can pass from mother to child across generations.
- Blocking the asprosin pathway in mice prevented both weight regain after dieting and inherited obesity risk, suggesting a potential complementary target to use alongside or after GLP-1 receptor agonist treatment.
Two long-standing puzzles in obesity research
Two biological mysteries have resisted explanation for decades. The first is why almost everyone who loses weight eventually regains it, regardless of the method used to lose it. The second is why obesity is transmitted from mother to child at rates that diet and environment alone cannot account for. Scientists from the Harrington Discovery Institute at University Hospitals and Case Western Reserve University now believe they have identified the reason behind both.
In a study published in Cell Reports, the research team found that obesity produces a durable biological change within fat cells that keeps the hunger hormone asprosin elevated – a phenomenon the researchers describe as “obesity memory” – even once weight has been lost. The findings may help to explain why many people regain weight after dieting or after discontinuing GLP-1 medications, and why obesity risk can persist from one generation to the next.
An appetite signal stuck in the on position
“Imagine having an appetite-stimulating signal stuck in the ‘on’ position day after day, despite losing weight,” explained Atul Chopra, M.D., Ph.D., senior author of the study, investigator and associate director of the Harrington Rare Disease Program at Harrington Discovery Institute at UH, and associate professor of medicine, genetics and genomics at Case Western Reserve University School of Medicine.
“Our findings suggest one reason weight regain can be so difficult to prevent after treatment ends. This same signal can also cross the placenta from mother to baby. The result is a child born with a programmed susceptibility to obesity. This may also explain why obesity became an epidemic and why the cycle has continued for generations.”
The observation that weight regain and intergenerational risk are near-universal features of obesity is not new. What has been missing is the underlying molecular explanation.
“These patterns have been observed for decades, but nobody knew the exact molecular mechanism that makes obesity so persistent or how it transmits across generations,” Chopra added. “We wanted to find the biological basis for that persistence.”
A switch that stayed on
The team began the study by looking for what turns up production of the hunger hormone asprosin in obesity. They identified an inflammatory signal, TGF-β1, as the trigger. The most striking result was that only a brief exposure to that signal was required to create a lasting change, one that persisted for weeks after the signal itself had disappeared.
“It was like flipping a light switch that stays on even after you remove your finger,” Chopra said. “Even after mice lost all the excess weight and TGF-β1 returned to normal, this switch in their fat cells remained flipped, keeping asprosin and appetite elevated.
“This gives us a molecular explanation for why GLP-1 drugs, which suppress appetite while you take them, cannot fix the underlying biological memory that drives hunger back up once treatment ends. This same signal crosses the placenta and programs a baby’s fat cells before birth.”
In other words, the change in fat tissue is epigenetic rather than temporary. The cells retain a record of the obesity they were exposed to, and that record continues to drive hunger long after body weight has normalised.
What this means for GLP-1 therapy
The mechanism offers an explanation for a pattern already familiar to clinicians: people taking GLP-1 medications frequently regain weight once they discontinue treatment. The medication suppresses appetite for as long as it is taken, but it does not erase the epigenetic memory held in fat cells. When the pharmacological brake is released, the underlying appetite signal is still switched on.
This has practical implications for how GLP-1 therapy is planned, discussed and supported in practice, particularly around the point of discontinuation. Structured professional development in this area – such as the College of Contemporary Health’s GLP-1RA Therapy: The Complete Programme short course – can help clinicians set realistic expectations with patients from the outset and plan for the period after treatment ends, rather than treating regain as an unexpected failure.
Pharmaceutical companies are actively searching for ways to help people maintain weight loss once treatment stops. The new findings identify a potential complementary target: a pathway that may sustain the biological drive towards regain after weight reduction.
Blocking asprosin changed the outcome
The researchers also tested what happened when the asprosin pathway was interrupted in mice, from the gene that produces the hormone through to the receptor in the brain that responds to it. Blocking this pathway prevented both weight regain after dieting and the inherited obesity risk passed to offspring.
That result points towards new therapeutic strategies aimed directly at the relapse problem that drug developers are currently trying to solve.
Evidence beyond a single laboratory
The study was deliberately designed to test its central observation outside the laboratory that made it. A separate laboratory led by Seth J. Field, M.D., Ph.D., independently reproduced the key persistence finding. Field is director of physician-scientist programs and chief scientific officer at the Harrington Discovery Institute at UH and a professor at Case Western Reserve School of Medicine.
Analyses of publicly available mouse and human datasets produced further supporting evidence. Additional human research is still needed, but the convergence across separate laboratories and independent datasets strengthens the case that this mechanism warrants serious investigation.
A message for clinicians
Chopra said the central message for clinicians is that obesity relapse is not a failure of willpower or discipline. It is driven by a durable biological memory written into fat tissue, which sustains hunger long after the weight has come off.
“We need to treat obesity as a condition that leaves lasting biological scars, not just a temporary state of excess weight,” he said.
Framing obesity in these terms has consequences for how conversations with patients are conducted. If regain reflects a persistent biological signal rather than a lapse in personal effort, then the clinical focus shifts towards long-term management and realistic planning for the period after active treatment.
Turning to human trials
The critical next step is translating these findings into people. The researchers plan to confirm that the same epigenetic memory operates in human fat tissue after weight loss, and to test whether therapies that block asprosin, or that reset these epigenetic marks, can prevent weight regain in people.
“Given the need for durable obesity treatments, we are interested in whether asprosin-blocking therapies could be used alongside or after GLP-1 treatment to prevent rebound,” Chopra concluded.
CCH insight
Research of this kind is changing how weight regain is understood and discussed in the consultation room. The College of Contemporary Health’s GLP-1RA Therapy: The Complete Programme CPD short course is designed for healthcare professionals who prescribe or support people using GLP-1 receptor agonists, including the practical questions that arise around initiation, ongoing support and discontinuation.
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Walking 8,500 Steps a Day May Help Prevent Weight Regain, Study Finds
Key Takeaways:
- New research presented at ECO 2026 suggests that walking around 8,500 steps a day may help people maintain weight loss and reduce the risk of weight regain after dieting.
- Researchers found that people who increased and sustained their daily step count were more successful at keeping weight off over the long term.
- The study highlights walking as a simple, affordable, and accessible strategy that could support long-term obesity management.
Study explores the role of walking in long-term weight management
New research being presented at the European Congress on Obesity (ECO 2026) in Istanbul, Turkey, taking place from May 12–15, suggests that walking approximately 8,500 steps per day could help people avoid regaining weight after dieting.
The findings, which will also be published in the International Journal of Environmental Research and Public Health, address one of the biggest challenges in obesity care – maintaining weight loss over time.
Although many weight loss programmes encourage people to increase their daily physical activity, including walking, researchers say there has been relatively limited evidence examining whether higher step counts genuinely help people lose weight during dieting or maintain that weight loss afterwards.
The new study aimed to clarify whether walking more each day could reduce the likelihood of weight regain and identify what level of daily activity may be most beneficial.
Preventing weight regain remains a major challenge
Professor Marwan El Ghoch, from the Department of Biomedical, Metabolic and Neural Sciences at the University of Modena and Reggio Emilia in Italy, highlighted the importance of addressing weight regain in obesity treatment.
“The most important – and greatest – challenge when treating obesity is preventing weight regain,” explained Professor El Ghoch.
“Around 80% of people with overweight or obesity who initially lose weight tend to put some or all of it back on again within three to five years.
“The identification of a strategy that would solve this problem and help people maintain their new weight would be of huge clinical value.”
Long-term weight maintenance is widely recognised as one of the most difficult aspects of obesity management. While many people can initially lose weight through dietary changes, sustaining those results often proves far more challenging due to complex biological, behavioural, and environmental factors.
Researchers conducted a large systematic review and meta-analysis
To explore the relationship between walking and long-term weight management, Professor El Ghoch and colleagues from Italy and Lebanon carried out a systematic review and meta-analysis of existing research.
The researchers analysed 18 randomised controlled trials investigating walking and weight management strategies. Fourteen of those studies, involving a total of 3,758 adults, were included in the final meta-analysis.
Participants had an average age of 53 years and an average body mass index (BMI) of 31 kg/m², placing the average participant in the obesity category. The studies included participants from a range of countries, including the United Kingdom, United States, Australia, and Japan.
The trials compared two groups:
- 1,987 participants enrolled in lifestyle modification (LSM) programmes
- 1,771 participants assigned to control groups
The control groups either followed dieting programmes without additional support or received no treatment intervention.
Lifestyle programmes combined diet and increased walking
The lifestyle modification programmes combined dietary guidance with recommendations to increase walking and monitor daily step counts.
These interventions generally included two distinct phases:
- An initial weight loss phase
- A longer-term maintenance phase designed to help participants sustain weight loss
Researchers assessed participants’ daily step counts at multiple time points throughout the studies, including:
- At baseline
- After the weight loss phase
- After the maintenance phase
The average duration of the weight loss phase was 7.9 months, while the maintenance phase lasted an average of 10.3 months.
At the start of the studies, physical activity levels were similar in both groups. Participants in the lifestyle modification programmes averaged 7,280 steps per day, while participants in the control groups averaged 7,180 daily steps.
Higher step counts were associated with less weight regain
The researchers found that participants in the control groups did not significantly increase their daily walking levels and did not experience meaningful weight loss during the studies.
In contrast, participants enrolled in the lifestyle modification programmes increased their average daily step count to 8,454 steps by the end of the weight loss phase.
During this period, participants lost an average of 4.39% of their body weight, equivalent to approximately 4 kg.
Importantly, participants were largely able to maintain their higher levels of daily activity throughout the maintenance phase. By the end of the studies, they were still averaging 8,241 steps per day.
They also maintained most of their weight loss over the longer term, with an average sustained weight reduction of 3.28%, or roughly 3 kg.
Further analysis demonstrated a clear association between higher daily step counts and lower levels of weight regain.
Researchers found that people who increased their walking during the weight loss phase and sustained those higher activity levels afterwards were more successful at maintaining weight loss over time.
Walking appeared more important for weight maintenance than initial weight loss
Interestingly, the study found that walking more was not associated with greater weight loss during the initial dieting period itself.
Researchers suggested this may be because calorie reduction and dietary changes tend to have a stronger influence on short-term weight loss than physical activity alone.
However, physical activity appeared to play a more significant role in helping people sustain weight loss once it had been achieved.
This distinction is important because many obesity interventions focus heavily on initial weight reduction, despite evidence showing that long-term maintenance is often the more difficult challenge.
A simple and affordable intervention
Professor El Ghoch said the findings demonstrate that lifestyle modification programmes incorporating walking can support clinically meaningful long-term weight management.
He added:
“Participants should be always encouraged to increase their step count to approximately 8,500 a day during the weight loss phase and sustain this level of physical activity during the maintenance phase to help prevent them from regaining weight.
“Increasing the number of steps walked to 8,500 each day is a simple and affordable strategy to prevent weight regain.”
The researchers suggest that walking may represent a practical and accessible intervention that could be incorporated into obesity treatment programmes without the need for expensive equipment or specialist facilities.
As obesity rates continue to rise globally, strategies that are sustainable, low-cost, and easy to implement may become increasingly important in supporting long-term health outcomes.
CCH insight
The evidence increasingly points to sustained behaviour change – not just the initial loss – as the real challenge in obesity care. CCH’s Obesity Essentials CPD short course (8–10 hours, fully online, CPD-accredited) gives healthcare professionals the practical skills to assess, support and manage patients with overweight and obesity, including how to help them build and maintain the everyday habits, such as regular walking, that keep weight off for good.
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