Immune Cells May Keep a Biological Memory of Obesity
Key Takeaways:
- Mice lacking a protein called CWC22 in their fat tissue immune cells struggled to lose weight on a reduced-fat diet.
- Over half of the obesity-related genetic changes in these cells persisted after weight loss, suggesting a biological “memory” of obesity.
- Correcting one of those changes restored normal cell function and helped the mice shed fat again.
Why weight loss can become harder after obesity
According to the World Health Organization, one in eight people worldwide lives with obesity. Yet despite the volume of health education programmes, books, articles and treatments available, many people continue to find weight loss extremely difficult once obesity has developed. Precisely why the body resists losing weight, and why lost weight is so often regained, remains a complex puzzle for researchers.
A new study published in the journal Science Translational Medicine may offer part of the answer. The research points to changes in a particular type of immune cell known as an adipose tissue macrophage (ATM). In mice, these changes appeared to make weight loss harder, because the cells seem to carry a biological “memory” of obesity that outlasts the obesity itself.
What the researchers did
Researchers from several institutions across Japan set out to study ATMs directly. These immune cells help regulate fat tissue health in a number of ways, one of the most important being the safe removal of dying cells from the tissue.
The team fed laboratory mice a high-fat diet for 12 weeks until the animals developed obesity, then switched them to a low-fat diet for a further six weeks. When they compared the animals, they noticed a pattern: the mice that lost the least weight after the dietary switch had lower levels of a protein called CWC22 in the nucleus of their ATM cells. This suggested that CWC22 might play a role in helping the body shed weight.
To test that idea, the researchers genetically modified a group of mice so that they lacked the CWC22 gene in a group of immune cells that includes macrophages. Under normal circumstances, CWC22 helps cells splice messenger RNA, the editing process that RNA undergoes before it is used as a template to make proteins.
A clean-up failure in fat tissue
When the modified mice were placed on a weight-loss diet, they struggled to shed fat. Their ATMs could not clear away dead cells effectively, and as a result dead cells accumulated in the fat tissue.
Closer analysis of these immune cells revealed the mechanism. The absence of the Cwc22 gene caused a splicing error involving a gene called Scarb1. Because of that error, the macrophages destroyed their own clean-up receptors before those receptors could reach the cell surface, leaving the cells without the tools they needed to do their job.
The knock-on effect involved a chemical messenger. Because the macrophages were less able to clear dead cells, they released less inosine. Inosine normally acts as a signal instructing fat cells to break down their stored fat, so with less of it available, fat breakdown was impaired.
A memory that persists after weight loss
Perhaps the most striking finding concerned how long these changes lasted. The research team found that 51.9% of the genes showing obesity-induced RNA splicing changes in these immune cells remained altered even after the animals had lost weight.
In other words, the immune cells retained a biological record of the period of obesity, including alterations that continued to impair their normal clean-up duties long after the diet had changed.
“These findings reveal that aberrant alternative splicing in macrophages underlies resistance to postobesity weight loss,” commented the study authors in their paper.
Rewriting the memory
Encouragingly, at least one component of that memory appears to be reversible. When the scientists corrected the Scarb1 splicing error using a synthetic genetic patch, the clean-up receptors were restored. This in turn increased the amount of inosine available and helped the mice to lose fat once again.
“Our study suggests that specific alternative splicing events can shape macrophage phenotypes under defined environmental conditions.”
What this could mean for people living with obesity
The findings may eventually help inform treatments for people who struggle to lose weight after developing obesity. When the team analysed human tissue samples, they found abundant CWC22 in the nuclei of immune cells taken from people who were lean, but reduced levels in samples from people living with obesity. That parallel between the mouse and human findings is what makes the work potentially translatable.
It is worth keeping the limitations in view. The functional experiments were carried out in mice, and the human element of the study was limited to tissue analysis rather than any test of treatment. No synthetic genetic patch has been trialled in people, and there is a considerable distance between correcting a splicing error in a mouse model and offering a therapy in clinical practice.
Even so, the study adds to a growing body of evidence that weight regain is not simply a matter of behaviour or willpower. Biological adaptations in fat tissue, appetite regulation and now immune cell function all appear to work against sustained weight loss. Clinicians who want to explore these mechanisms and their practical implications in more depth may find it useful to look at structured CPD, such as the College of Contemporary Health’s Obesity Essentials short course, which covers the biological, clinical and behavioural drivers of obesity and weight management.
For people living with obesity, findings like these carry a useful message: the difficulty of maintaining weight loss has measurable biological underpinnings, and understanding them may in time lead to better-targeted support.
CCH insight
Understanding why the body resists weight loss is central to supporting people living with obesity well. Our Obesity Essentials CPD short course explores the physiology, clinical management and behavioural dimensions of obesity, giving healthcare professionals a grounded, evidence-informed basis for the conversations they have every day.
Read More
Daily Tomato Intake May Lower Liver Fat in People With MASLD, New Study Suggests
Key Takeaways:
- In a six-week randomised study of 79 adults with metabolic dysfunction-associated liver disease (MASLD), people who ate 200 grams of raw tomatoes and 50 grams of tomato sauce each day showed a greater reduction in hepatic steatosis than people following a tomato-free control diet.
- Liver fat fell in both groups, and researchers found no meaningful differences between the groups in liver stiffness, liver enzymes, lipids or body mass index after the intervention period.
- Independent specialists described the findings as exploratory rather than practice-changing, noting the short duration, the narrow participant profile and the absence of improvement in clinically relevant markers.
What the research set out to examine
Metabolic dysfunction-associated liver disease (MASLD) covers a spectrum of liver problems, but its defining feature is hepatic steatosis – the accumulation of fat within the liver. A diagnosis also requires the presence of at least one cardiometabolic risk factor, such as obesity or high blood pressure.
Diet and lifestyle changes are a mainstay of support for people living with MASLD, and researchers are increasingly interested in whether particular foods offer measurable advantages over others. A study published in Nutrients set out to test one such food: the tomato, a staple of the Mediterranean diet.
The research team wanted to establish whether regular tomato consumption would influence liver steatosis in people who already had a MASLD diagnosis.
How the study was designed
The study enrolled 79 adults with MASLD. Researchers applied a number of exclusion criteria, ruling out people who consumed above a set threshold of alcohol and those with a body mass index above 30, the point at which obesity is classified.
Participants were divided into two groups. One group followed a tomato-free control diet. The other consumed 200 grams of raw tomatoes and 50 grams of tomato sauce daily. All tomato products were supplied by the same producer to keep the intervention consistent, and participants were asked to carry on with their usual lifestyle in every other respect.
The intervention ran for six weeks. Across that period, researchers tracked a range of health indicators, including body composition, hepatic steatosis, liver stiffness and cholesterol levels.
What the researchers found
Hepatic steatosis declined in both groups over the six weeks. The decrease was greater, however, among people in the tomato group.
Further analysis showed that hepatic steatosis had been broadly similar between the two groups at baseline, which strengthens the comparison. Other measures told a quieter story. Researchers identified no major changes in liver stiffness, and no significant differences between the groups in lipids, liver enzymes or body mass index at the end of the six-week period.
Summarising the result, the authors suggested that “tomato consumption may reduce hepatic fat accumulation independently of major changes in body weight, total and abdominal adiposity.”
Because liver fat shifted while weight and body composition did not, the study raises a familiar practical question for clinicians: how far can dietary composition alone move metabolic outcomes when overall energy intake stays broadly the same? It is the kind of question CCH explores in its CPD short course Nutrition & Weight Management Essentials, which examines the relationship between modern nutrition and weight, and how evidence-based dietary advice translates into everyday clinical conversations.
Study limitations and continued research
The six-week window is short, so the study cannot speak to whether any benefit persists over the longer term. The research also recruited only adults aged 65 and under, leaving it unclear how the findings might apply to older adults.
Most participants were men, so more balanced recruitment would strengthen future work. The decision to exclude people with a body mass index above 30 also narrows how widely the results can be applied.
Endocrinologist and obesity specialist Randa Abdelmasih MD, DipABOM, from the University of Texas Medical Branch (UTMB), who was not involved in this study, told Medical News Today:
“The study demonstrates a modest reduction in hepatic steatosis over only six weeks in a highly selected population of adults with MASLD and BMI [body mass index] of 30 kg/m² [kilograms per square meter] or more. Most patients we see in clinical practice have obesity (BMI over 30 kg/m²), type 2 diabetes, or more advanced metabolic disease, so the generalizability of these findings is limited.”
Jonathan Jennings, MS, MD, a board-certified internist with Medical Offices of Manhattan, who was likewise not involved in the research, raised a related concern about how participants were selected.
“The inclusion criteria required only one cardiometabolic risk factor, and it could be any risk factor. I am concerned that not all risks are equal, and people with multiple factors are at higher risk than those with a single risk factor,” Jennings said.
“Type 2 diabetes is more likely to lead to MASLD than high blood pressure but the study evaluates them as equal risk factors,” he pointed out.
The researchers themselves note that the reduction in liver fat may have been influenced by other factors, including the effect that taking part in a dietary intervention study can have on participants’ behaviour. The team was also reliant on dietary counselling and on participants’ own reports of how closely they followed the intervention.
Abdelmasih added that because the intervention combined raw tomatoes with tomato sauce, it is “difficult to determine which component or combination was responsible for the observed effect.”
A further gap is that researchers did not measure circulating levels of lycopene and carotenoids, the compounds most often proposed as the mechanism behind any effect tomatoes might have on liver health.
Limited clinical application at this stage
The authors describe their study as exploratory, intended primarily to inform future research. They call for confirmation through larger and longer studies, and encourage readers to treat the findings as hypothesis-generating rather than conclusive.
The clinical value is also uncertain because so much else stayed the same. As Abdelmasih put it:
“The study showed improvement in liver fat but no significant improvements in liver stiffness, fibrosis scores, liver enzymes, insulin resistance, inflammatory markers, lipid profile, or body composition. Therefore, while the imaging findings are interesting, we cannot conclude that tomato consumption meaningfully alters disease progression or improves clinically relevant outcomes.”
What this means for people living with MASLD
Within its limits, the study does point to a possible benefit of tomato consumption for people with MASLD, and to a low-cost dietary strategy that may help with fat accumulation in the liver.
Tomatoes may carry other advantages too, with existing research pointing towards cardiovascular benefits and potential anti-cancer properties.
Even so, the sensible route is for people to work with their doctor and wider healthcare team on a dietary plan that addresses their overall health, rather than concentrating on any single food.
Jennings underlined that point, and flagged two practical cautions:
“The study’s conclusions are hopeful but careful discussion with a healthcare provider is still needed before engaging in any radical dietary adjustments. Tomatoes and tomato-based products may be problematic for individuals with gastroesophageal reflux disease (GERD). Many tomato-based foods are also calorically dense and may worsen insulin resistance in certain individuals.”
The broader treatment context matters as well. According to Abdelmasih: “Dietary interventions should be viewed within the broader context of treating the underlying metabolic disease. For patients with obesity, sustained weight loss of approximately 10% or more remains the intervention with the strongest evidence for improving steatohepatitis and fibrosis.”
“While tomatoes can certainly be part of a healthy Mediterranean diet, they should not distract from therapies that have demonstrated meaningful improvements in liver and cardiometabolic outcomes,” she concluded.
CCH insight
Conversations about diet sit at the centre of metabolic and liver care, and single-food headlines can make those conversations harder rather than easier. CCH’s CPD short course Nutrition & Weight Management Essentials gives healthcare professionals a grounding in the fundamentals of nutrition, the factors driving weight gain, and what effective weight management looks like in practice – so you can place findings like these in proportion for the people you support.
Explore Nutrition & Weight Management Essentials →
Expert commentary in this article was provided to Medical News Today. Read the original report here.
Read More
Belly Weight Predicts Heart Health Better Than BMI, Study Indicates
Key Takeaways:
- Fat stored around the waist is a stronger predictor of heart disease than body mass index alone.
- People with preclinical obesity face a raised cardiovascular risk despite appearing healthy.
- Researchers estimate early intervention could prevent 45% of new cardiovascular disease cases.
Why waist size matters more than the scales
People living with overweight or obesity can carry a higher risk of heart disease even when they appear to be perfectly healthy, according to new research presented at the International Congress on Obesity in Mexico City (15–17 July). Combining waist-based measurements with body mass index (BMI) to detect this hidden risk and act early could, over the years ahead, prevent hundreds of thousands of people from dying from heart attacks, strokes and other cardiac problems, researchers from the University of Glasgow, Glasgow, UK, said.
“We know that excess weight, particularly around the waist, increases the risk of heart disease,” said lead researcher Estefania Fuentes Avalos. “In 2021, an estimated 1.9 million cardiovascular disease deaths – almost one in 10 heart-related deaths worldwide – were attributed to high body mass index.
“The link between central, or abdominal, obesity and heart disease is especially strong because fat stored around the waist, known as visceral fat, is metabolically active and releases inflammatory substances into the bloodstream. Over time, this chronic inflammatory state can damage blood vessels and accelerate the buildup of arterial plaque, significantly increasing the risk of heart attacks.”
The limits of BMI
BMI, a measure of weight compared with height, is routinely used to assess a person’s weight status, defining whether they have a normal weight, overweight or obesity. However, it does not take into account where fat is stored in the body.
To address this and other shortcomings of BMI, The Lancet Diabetes & Endocrinology Commission recently proposed a different way of assessing obesity status. The Lancet Commission framework uses BMI together with central adiposity markers – waist measurements – to determine whether a person has excess body fat. People with excess body fat are then categorised as having either preclinical obesity or clinical obesity, depending on whether they also have long-term obesity-related conditions such as high blood pressure, joint pain and sleep apnoea.
The new study set out to establish whether this method is better at identifying people at high risk of cardiovascular disease than BMI alone.
“Detecting cardiovascular risk at an early stage is essential, particularly at the preclinical stage of obesity, as it provides a window of opportunity to implement timely, targeted interventions before obesity-related complications such as high blood pressure arise,” Fuentes Avalos said.
“This underpins our focus on risk stratification in this group, with the aim of detecting high-risk individuals who may otherwise be overlooked.”
What the study looked at
Fuentes Avalos examined data on 382,769 adults of white ethnicity in the UK Biobank study (age range 40–69 years, average age 56 years, 53% women).
Under The Lancet Commission framework, 285,190 (74%) of the participants had excess body fat, based on BMI and central adiposity markers. Within this group, 102,237 (26.7%) were classified as having preclinical obesity – excess body fat without long-term obesity-related conditions – and 182,953 (47.8%) as having clinical obesity, meaning excess body fat alongside long-term obesity-related conditions. The remainder had neither excess body fat nor long-term obesity-related conditions; they were classified as not having obesity and served as the reference group.
None of the participants had cardiovascular disease at the start of the study. Hospital and death records provided information about diagnoses of, and deaths from, heart attacks, strokes and other forms of cardiovascular disease over the following 12 years. During this time, there were 41,742 new cases of, and 8,832 deaths from, cardiovascular disease. Studies of this scale underline how much practical assessment skill clinicians need when supporting patients with excess weight – a competency CCH’s Obesity Essentials short course is designed to build.
Clinical obesity carried the sharpest risk
Analysis of the data showed that people with clinical obesity were far more likely to develop, or die from, cardiovascular disease than those without obesity.
Women with clinical obesity developed cardiovascular disease at a rate 2.5-fold higher than women without obesity, and died from it at an almost threefold (2.8-fold) higher rate. Men with clinical obesity developed cardiovascular disease at an almost twofold higher rate (1.9-fold) and had a 2.6-fold higher rate of cardiovascular death than men without obesity.
The hidden risk in preclinical obesity
People with preclinical obesity were also at greater risk, despite having no obesity-related conditions and appearing to be in good health.
Women with preclinical obesity developed cardiovascular disease at a 38% higher rate and died from it at a 46% higher rate than women without obesity. For men, preclinical obesity was associated with an 18% higher rate of developing cardiovascular disease and a 52% higher rate of cardiovascular death.
All of the results were adjusted for socioeconomic status and lifestyle factors, including smoking and alcohol consumption.
More waist markers, more risk
Further analysis showed that the more high-risk central adiposity markers a person had, the more likely they were to develop heart disease. For example, a woman with one high-risk marker – waist circumference, waist-to-hip ratio or waist-to-height ratio – was 17% more likely to develop cardiovascular disease than a woman with no high-risk waist measurements. Having all three high-risk measurements increased the risk by 64%. The study also found that waist measurements were more accurate at predicting cardiovascular disease than BMI.
A window of opportunity
The researchers concluded that people with preclinical obesity are at higher risk of developing, and dying from, cardiovascular disease despite appearing to be healthy.
“Preclinical obesity is a critical window of opportunity to improve heart health. Routinely measuring waist circumference, waist-to-hip ratio and waist-to-height ratio along with BMI would identify high-risk individuals who might be overlooked by assessing BMI alone,” Fuentes Avalos said.
“They could then be offered intensive diet and exercise programs to improve their cardiac and overall health.
“We have calculated that early intervention could prevent 45% of new cases of cardiovascular disease and 41% of cardiovascular disease deaths in similar populations.
“Given that cardiovascular disease remains a leading cause of ill health and death globally, routinely taking waist measurements along with BMI could prevent hundreds of thousands of deaths over a decade alone.”
CCH insight
This is very important work on two levels. Firstly, it not only re-enforces the importance of waist circumference measures as superior indicators of disease risk compared to the traditional BMI measure, but also suggests that calculating three waist circumference markers gives a more accurate indication of CV risk than just one. And secondly, it feeds into the current debate around the terms ‘clinical’ and ‘pre-clinical’ obesity coined by The Lancet Diabetes & Endocrinology Commission. The results indicate that, while people with clinical obesity have a far higher risk of cardiovascular disease or death, those with pre-clinical obesity are still at risk and still therefore warrant intervention. Depending on your perspective, you could argue this supports the Commission’s findings or contradicts them!
Findings like these are only useful in practice if clinicians feel confident assessing excess weight and having sensitive, evidence-based conversations with patients about it. CCH’s Obesity Essentials – an online CPD short course offering 10 CPD hours – equips healthcare professionals with the practical skills to assess and manage patients living with overweight and obesity, from measurement through to compassionate communication.
Explore Obesity Essentials and strengthen your day-to-day weight-management practice.
Read More
Tirzepatide May Activate Calorie-Burning Brown Fat in Obesity, Trial Suggests
Key Takeaways:
- Findings from the TABFAT trial, presented at ENDO 2026, indicate that tirzepatide does more than curb appetite – it also appears to activate brown adipose tissue, a heat-producing fat that burns calories.
- Among premenopausal women with obesity, the proportion with PET/CT-detectable brown fat activity rose from 41.2% to 64.7% after 24 weeks of treatment, with no comparable change in the placebo group.
- Researchers also saw potential signs of white fat taking on more metabolically active “beige” characteristics, pointing towards future therapies that pair appetite control with increased energy expenditure.
Beyond appetite: a different question
For people taking tirzepatide, weight loss has so far been explained mainly by a reduced appetite and the smaller portions that follow. New research suggests the picture may be more complex. The medication appears to do more than dampen hunger – it also seems to switch on brown adipose tissue, a metabolically active fat that generates heat and consumes calories. The findings, described by the research team as a notable milestone in obesity research, were due to be presented on Monday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
The study set out to look past the appetite-suppressing effect that has dominated explanations of how these medications work. As lead investigator Rok Herman, M.D., of the Department of Endocrinology, Diabetes and Metabolic Diseases at University Medical Centre Ljubljana in Ljubljana, Slovenia, put it: “In the TABFAT trial, we asked a different question: beyond eating less, does tirzepatide also change how the body burns energy – specifically through brown adipose tissue, a metabolically active type of fat that produces heat and consumes calories?”
What is brown adipose tissue?
Brown adipose tissue, often referred to as brown fat, was for many years thought to disappear after infancy. Its presence in adults was only confirmed through imaging studies in the late 2000s. Unlike ordinary white fat, which mainly stores energy, brown fat burns it to produce heat. In people living with obesity this tissue is markedly suppressed, and until now moderate cold exposure has been its strongest recognised activator.
How the TABFAT trial was designed
The team led by Herman ran a randomised, placebo-controlled clinical trial in premenopausal women with obesity. To assess what was happening within the tissue itself, the researchers used cold-stimulated PET/CT imaging alongside MRI scans, measuring brown adipose tissue activity both before treatment and after 24 weeks. Using more than one imaging method allowed the team to capture different aspects of brown fat biology rather than relying on a single measure.
What the scans revealed
The results pointed to a measurable change in how the body handled energy, not simply how much participants ate. “We found that tirzepatide significantly increased brown adipose tissue activity and volume, and it also showed potential signs of converting white subcutaneous fat into more metabolically active ‘beige’ fat,” Herman said.
The shift was clear in the imaging data. Tirzepatide increased PET/CT-detectable brown adipose tissue activity from 41.2% to 64.7% of participants, while no comparable change was seen in the placebo group. The researchers were reassured that the effect showed up across the different scanning techniques used. “We were also encouraged by the consistency of the signal across other imaging modalities employed in the study that may capture different component of brown fat biology,” Herman added.
Why this matters for obesity care
The findings suggest a fuller account of how the latest anti-obesity medications work. Rather than acting on appetite alone, tirzepatide also appears to influence how much energy the body burns at the level of the tissue. “This adds a new layer to how we understand the new generation of anti-obesity medications,” Herman said. “They are not only appetite suppressants – tirzepatide also appears to modulate energy expenditure at the tissue level, opening a plausible path toward future therapies that combine appetite regulation with thermogenic activation.”
Keeping pace with this fast-evolving mechanistic understanding of anti-obesity medications is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Focus, a CPD-accredited online short course that grounds clinicians in how these drugs work.
Looking ahead
Herman suggests that future research should measure, study and potentially enhance brown and beige fat activity, treating it as a specific target within a more tailored approach to obesity care. If brown fat activation can be reliably encouraged and built upon, it may complement the appetite-related effects already well documented, broadening the options available to people living with obesity.
CCH insights:
This is a fascinating study. For many years researchers have been looking at ways to stimulate brown adipose tissue (BAT) activity, or enhance beige adipose tissue production, without much success, except for asking people to spend hours in the cold every day. Now it seems we may have stumbled across an answer by accident. The question now is, how does tirzepatide have this effect, and could we develop other agents which act in a similar way to activate BAT and beige adipose tissue without affecting gastro-intestinal function and/or appetite? This would enable us to widen the range of tools for obesity care.
Following where questions like this lead – how a dual GIP/GLP-1 agent acts on energy expenditure and not just appetite – starts with a solid grounding in the underlying physiology, which is exactly what our two-hour CPD course GLP-1RAs in Focus – Why Drugs Like Ozempic Work is built to give any clinician wanting to understand these medications at the mechanistic level wanting to understand these medications at the mechanistic level.
Explore GLP-1RAs in Focus →
This article summarises findings presented at ENDO 2026, the Endocrine Society’s annual meeting. Research presented at conferences may not yet have completed full peer review.
Source: Endocrine Society
Read More
People with Obesity Tend to Move Less After Starting GLP-1 Medications, Study Finds
Key Takeaways:
- Daily step counts and moderate-to-vigorous activity both dropped after adults with obesity started a GLP-1 receptor agonist, with no sign that weight loss prompted people to move more.
- Because these medications strip away lean muscle as well as fat, staying active matters for protecting strength and long-term health rather than being an optional extra.
- This is the first large study to draw on data from wearable fitness trackers in adults taking GLP-1 medications, and its authors argue for targeted support that builds activity in alongside treatment.
A counterintuitive picture of how people move
It is tempting to assume that as the weight comes off, people naturally become more active. New findings suggest the opposite may be closer to the truth. Adults with obesity who were losing weight on glucagon-like peptide-1 (GLP-1) receptor agonist medications significantly reduced their physical activity, according to a study being presented on Saturday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
That matters because activity is one of the main safeguards against an unwanted side effect of these treatments. GLP-1 receptor agonists such as semaglutide, liraglutide, dulaglutide and tirzepatide reduce not only fat but also lean muscle mass. This makes physical activity essential for preserving strength and long-term health, according to study lead Sajana Maharjan, M.D., of HSHS St. John’s Hospital in Springfield, Illinois.
How the study was carried out
The work was a retrospective pre–post cohort study, meaning researchers compared the same individuals before and after they started treatment. It drew on data from the National Institutes of Health’s All of Us Research Program, which links participants’ electronic health records with their Fitbit activity data, allowing the team to track real-world movement rather than relying on self-reported habits.
Among the 1,950 adults with obesity who started a GLP-1 medication, researchers studied 753 people who had enough wearable-device data for analysis. The cohort was predominantly female, at 78.6 per cent, with a mean age of 52.7 years.
For each person, the researchers compared physical activity before and after treatment began, focusing on two measures: daily step counts and minutes of moderate-to-vigorous physical activity (MVPA).
Steps and active minutes both fell
The direction of travel was clear. On average, daily steps decreased from 5,047 to 4,487 per day, while MVPA minutes fell from 28 to 22 per day after people began a GLP-1 receptor agonist medication.
Crucially, the study found no evidence that weight loss from these medications led to increased physical activity. The expected rebound in movement simply did not appear in the data.
Who saw the biggest changes
The decline was not evenly spread. The largest drops were seen in men and in people living with joint or muscle pain. By contrast, factors such as age, heart failure or a prior stroke did not change the results, suggesting the pattern held across a fairly broad range of circumstances.
Why activity cannot be an afterthought
For Dr Maharjan, the practical message is that exercise needs to be designed into treatment rather than left to chance:
“While many assume that weight loss leads naturally to increased physical activity, our study suggests otherwise. The findings in our study reinforce that exercise cannot be optional for people taking these medications. People need targeted interventions that encourage physical activity alongside medication for obesity.”
Given that GLP-1 receptor agonists reduce lean muscle alongside fat, a fall in activity could compound the loss of strength, making structured support for movement an important part of care rather than a nice-to-have.
A first for wearable-data research
The study stands out for its method as much as its findings. It is the first large study analysing data from wearable fitness trackers among adults taking GLP-1 receptor agonists, offering a more objective window into everyday behaviour than questionnaires alone can provide. As these medications become more widely used, that kind of real-world evidence is likely to shape how clinicians and patients approach physical activity during treatment.
CCH insights:
This is a very interesting study, but it throws up more questions than answers. Firstly, were any of the participants receiving diet and lifestyle advice as they are supposed to? GLP-1 medications are designed as an adjunct to such advice, but these results suggest it was probably lacking from these patients’ treatment. Another question, of course, is why did physical activity drop? Further research is needed to understand what is the underlying reason for these results. But most importantly, this study is a reminder that GLP-1 therapy is not just about taking the medication, it requires diet and lifestyle advice and ongoing support and monitoring.
Source: Endocrine Society
Read More
Beyond the Scales: Why Physical Activity Remains Central to Obesity Care
Key Takeaways:
- Exercise earns its place in obesity care through benefits the scales never show – lower blood pressure, better insulin sensitivity and improved fitness – so it remains worthwhile even when weight changes little.
- On its own, activity shifts the scales only modestly, but paired with diet, obesity medications or surgery it protects lean muscle, drives fat loss and makes the results last.
- Tools such as the 5A consultation model, wearables and app-based coaching can lift adherence, though their value depends on access, accuracy and how well they fit each person’s life.
How much weight someone loses has long been the headline measure of whether obesity treatment is working. A new scientific statement from the American Heart Association, published in Circulation, makes the case that this measure misses much of what physical activity actually does. Movement, the statement argues, reshapes cardiovascular and metabolic health in ways that a set of weighing scales will never register.
What activity does that the scales cannot capture
Obesity sits at the centre of cardiovascular risk because of the company it keeps: raised blood pressure, disordered blood fats and insulin resistance. With roughly 42% of adults in the United States affected, the stakes are considerable, and treatment has traditionally pursued two linked aims, shedding weight and lowering heart disease risk.
Physical activity contributes to both, but the more interesting finding is how much it achieves on its own terms. Regular exercise lowers blood pressure, sharpens the body’s response to insulin and nudges cholesterol and other lipids in a healthier direction, and it does so whether or not the number on the scales falls. Aerobic and resistance training each deliver. As a rough rule, doing more tends to help weight-related outcomes most, while working harder pays off most for cardiorespiratory fitness.
Why exercise alone is a poor weight-loss strategy
If the goal is purely to lose weight, activity by itself is an inefficient route. Unless someone trains at high volumes, the losses are usually small, and fewer than one person in seven manages a clinically meaningful reduction through exercise alone. The body, in effect, fights back: appetite climbs and metabolism slows, eroding the deficit that training creates.
This is why exercise works best in combination. Adding it to a calorie-reduced diet produces more weight loss and better metabolic results than either approach in isolation. And the composition of that loss matters as much as the total. Eating enough protein and including resistance work helps ensure the weight that goes is fat rather than muscle, preserving the lean tissue that keeps metabolism and strength intact.
Keeping weight off is the harder battle
Losing weight is difficult; not regaining it is harder still, and regain tends to undo the health gains that came with it. Here the evidence points firmly towards higher activity levels, somewhere between 200 and 300 minutes a week, as a marker of people who keep weight off successfully. The catch is that few people sustain that volume.
A more realistic path is to build gradually towards at least 150 minutes a week of moderate-to-vigorous activity, then add more where possible. Even when some weight creeps back, staying active keeps the cardiometabolic benefits in play, which is reason enough to maintain the habit rather than abandon it after a setback.
Where medication and surgery enter the picture
For people whose body mass index is high and for whom lifestyle change has not been enough, obesity medications and bariatric surgery are central options. Both are effective, and both come with real-world limits around cost, availability and side effects. Neither replaces an active lifestyle; the statement frames physical activity as the strategy that should run alongside them.
The newer GLP-1 receptor agonists, including liraglutide, semaglutide and tirzepatide, have transformed what medication can achieve, with some trials approaching the results once seen only after surgery. They work mainly by curbing appetite and slowing the stomach’s emptying, and although side effects are common, they are usually manageable. Beyond weight, liraglutide and semaglutide have been shown to cut major cardiovascular events in certain high-risk groups.
What remains poorly understood is how exercise fits into this newer landscape. Most medication trials simply have not isolated what activity adds, or how the two interact, leaving the ideal exercise prescription for people on these drugs an open question. The issue is sharpened by the fact that a notable share of the weight lost on GLP-1 receptor agonists is lean tissue rather than fat, even if the long-term consequences of that are not yet clear. The handful of studies that do compare medication with and without exercise suggest that adding activity means more fat loss and better fitness, but the field is still waiting for the large, controlled trials that would settle the matter.
Surgery raises related questions. People approaching bariatric procedures tend to be less active to begin with, and there is no agreed playbook for the period beforehand; insurer-mandated pre-surgical activity programmes exist, but the evidence that they change outcomes is thin and inconsistent. Afterwards, the picture is clearer: people who move more lose more weight and fat, hold onto those losses, and gain in fitness and strength, though effects on metabolic risk markers vary and access to structured programmes is frequently lacking.
Turning good intentions into sustained habits
Clinicians are not bystanders in any of this. A widely used framework, the 5A model, gives consultations a useful spine: assess where the person is, advise on the options, agree on goals, assist in pursuing them and arrange follow-up. Worked through properly, each step tends to deepen engagement with both dietary change and activity, making healthy behaviours easier to stick to.
Doing this well means looking past activity levels alone to the psychological, social and medical factors that can stall progress, and gauging how ready and confident someone feels about changing. Counselling tailored to that profile builds motivation and trust, which in turn supports the activity itself. Equipping clinicians to weave physical activity, dietary change and behaviour change into everyday obesity consultations is the focus of practical training such as the College of Contemporary Health’s Obesity Toolbox, a CPD-accredited online short course. Because a short appointment can only do so much, part of the clinician’s job is helping people spot the obstacles in their way, solve them together, and connect with wider support, whether behavioural counselling or a digital programme that keeps them accountable between visits.
Technology is increasingly part of that support. Wearables, apps, text reminders, personalised feedback and self-monitoring all show promise for keeping people moving. The statement is careful, though, to flag the caveats: not everyone has equal access to these tools, the devices vary in how accurately they measure activity, and none of it substitutes for regular reassessment and structured follow-up.
The bottom line for treatment
Physical activity belongs at the heart of comprehensive obesity care, supporting weight loss, helping maintain it and improving health more broadly. Medications and surgery are genuine advances, but exercise adds something they do not fully provide: gains in cardiovascular risk, body composition, fitness and quality of life, many of which arrive independently of any change on the scales.
Delivering that well takes teamwork across clinicians and allied health professionals, and programmes that are not only effective but also affordable and within reach, especially for under-resourced communities where obesity is more common and activity levels lower. Making the wider case for movement, rather than treating it as a weight-loss tool alone, is likely to be what makes obesity treatment hold up over the long run and eases the cardiovascular toll that obesity exacts.
CCH insights:
This study strikes right at the heart of how our understanding of obesity is starting to change – it is not all about body weight and body fat, but about health. Although reducing harmful body fat is an important part of obesity treatment, so is improving cardiometabolic health and other health issues that arise as a result of obesity. And physical activity is a vital tool in delivering these health improvements – helping to reduce blood pressure, regulate blood glucose, reduce cholesterol and improve
muscle mass and function – whether or not it results in weight loss whether or not it results in weight loss. For clinicians looking to put this into practice, CCH’s Obesity Toolbox (1.5 hours, fully online, CPD-accredited) is a quick, practical primer on the essentials of physical activity, dietary change and behaviour change in obesity care – a fast starting point for busy practitioners.
Explore the Obesity Toolbox →
Four Weeks of Tomato-Soy Juice Lowered Inflammation in Adults with Obesity
Key Takeaways:
- In a four-week study, a tomato-soy juice rich in lycopene and soy isoflavones significantly reduced three blood markers of systemic inflammation in healthy adults with obesity, while a control tomato juice lacking those compounds did not.
- The researchers chose a low-carotenoid tomato juice as the comparison drink, rather than water, so they could isolate the effects of the lycopene and isoflavones rather than the effects of tomato juice in general.
- Building on these results and supporting animal data, the team has secured federal funding for a pilot clinical trial examining whether the same juice can ease inflammation in people living with pancreatitis.
A food-based approach to inflammation
Drinking a tomato-soy juice packed with plant compounds previously shown in animal studies to support health lowered pro-inflammatory proteins in healthy adults with obesity after four weeks, according to a new study. The researchers say the findings point to the juice’s potential as a functional food that could help rein in the persistent, unchecked inflammation that underpins a wide range of chronic conditions.
The juice was formulated to deliver high levels of two plant-based compounds, lycopene and soy isoflavones, both of which earlier research suggests have antioxidant and anti-inflammatory properties. Measured against a control tomato juice that lacked these compounds, the tomato-soy juice produced a significant drop in the blood levels of three proteins that serve as markers of systemic inflammation.
“The idea is, can we use food-based interventions to modulate inflammation?” said lead author Jessica Cooperstone, associate professor of horticulture and crop science at The Ohio State University. “And can we test this in a rigorous way so that we can really see this is affecting inflammation, versus just saying something is anti-inflammatory?”
The study was published recently in the journal Molecular Nutrition & Food Research.
What is in the juice
Lycopene is a carotenoid, the class of pigments responsible for the colours of tomatoes and various other vegetables. Soy isoflavones are flavonoids that mimic the action of the hormone oestrogen. Both are phytochemicals, naturally occurring compounds that help plants thrive.
Years ago, drawing on studies that linked diets rich in either tomato products or soy with a reduced risk of prostate cancer, Ohio State researchers developed the tomato-soy juice. It was made using tomatoes bred to contain a high concentration of lycopene – varieties also developed and grown at Ohio State – and then enriched with a soy isoflavone extract.
Subsequent research at the university connected a higher intake of the tomato-soy juice with reduced prostate-specific antigen levels in some men with prostate cancer. Studies conducted elsewhere have likewise suggested that tomatoes and soy, whether eaten separately or together, can influence inflammatory and metabolic pathways tied to obesity and other chronic illnesses.
“There’s been enough compelling evidence that compounds from tomatoes and soy might be modulating inflammation that we decided to test this in people,” Cooperstone said.
How the study was carried out
For the new study, 12 healthy adults with obesity drank two 6-ounce cans of the tomato-soy juice every day for four weeks. Following a washout period, the same participants then consumed the low-carotenoid control tomato juice for a further four weeks.
The choice of comparison drink was deliberate. Rather than pitting the juice against plain water, the team selected a tomato juice stripped of the key compounds so that any difference could be attributed to those compounds specifically.
“The hypothesis is that it’s the lycopene from the tomatoes and the isoflavones from the soy that’s inducing the effect, so we didn’t want to have a control that’s just water,” Cooperstone said.
What the blood tests showed
Before and after each four-week period, the researchers collected blood samples and tested them for cytokines, the pro-inflammatory proteins produced by the immune system. Only the tomato-soy juice produced significant reductions, and it did so in three cytokines: interleukin (IL)-5, IL-12p70 and granulocyte-macrophage colony-stimulating factor (GM-CSF). The juice was also associated with a downward trend in tumour necrosis factor alpha (TNF-a), although that particular change did not reach statistical significance.
Clues from the urine analysis
The team also examined participants’ urine before and after each trial period, looking for changes in metabolites. Metabolites are the molecular products of the biochemical reactions that break down nutrients to generate energy and carry out other essential functions in the body.
The analysis revealed that both the tomato-soy juice and the control tomato juice prompted some of the same shifts in metabolite profiles, indicating that certain tomato-driven effects occurred even in the absence of lycopene. Among the changes specifically induced by the tomato-soy juice, shifts in soy isoflavone metabolites stood out. The researchers note that, while more investigation is warranted, these changes offer further evidence that the food-based intervention is acting on human biology.
“This is probably a function of the fact that there’s more to our intervention agents than just these two compounds,” Cooperstone said. “Ultimately, we want to have a better understanding of how the foods that we eat are relating to our health. And when we really want to be sure, we need to test them in clinical trials. And that’s what we’re doing here.”
Next steps: a pancreatitis trial
On the strength of these results and additional data, Cooperstone and her colleagues have received funding from the National Institute of Diabetes and Digestive and Kidney Diseases for a pilot clinical trial. That trial will test whether consuming the same tomato-soy juice reduces inflammation in people living with pancreatitis.
The team has also gathered evidence from an animal model suggesting that the tomato-soy juice can lessen both inflammation and the severity of chronic pancreatitis. Those findings support the central prediction behind the new clinical trial, namely that the intervention could improve outcomes for people with the condition.
“Care for patients with pancreatitis is palliative, focused on controlling pain and GI symptoms. Our hypothesis is that the tomato-soy juice may serve as an intervention to decrease inflammation and hopefully increase patients’ quality of life,” Cooperstone said.
Funding and contributors
The work was supported by the U.S. Department of Agriculture, the National Institutes of Health, the Lisa and Dan Wampler Endowed Fellowship for Foods and Health Research, and the Foods for Health Initiative at Ohio State.
Co-authors include first author Maria Sholola, along with Jenna Miller, Emma Bilbrey, David Francis and Thomas Mace, all of Ohio State, and Janet Navotny of the USDA. Mace is the lead principal investigator on the pancreatitis trial. Cooperstone, Philip Hart and Kristen Roberts of Ohio State are also principal investigators on that trial.
Source: Eureka Alert!
Read More
Year-Long Trial Finds Rapid Weight Loss Outperforms a Gradual Approach, Overturning a Long-Held Assumption
Key Takeaways:
- In a 52-week randomised trial, adults living with obesity who followed a rapid weight loss programme lost significantly more weight at one year than those on a gradual programme (14.4% versus 10.5% of total body weight), and the gap held throughout the study.
- Rapid weight loss was not associated with greater weight regain, directly contradicting the widespread belief that losing weight slowly is necessary to keep it off.
- A larger share of people in the rapid weight loss group reached clinically meaningful BMI and waist-to-height targets linked to a lower 10-year risk of obesity-related conditions.
A long-held belief comes under scrutiny
New research presented at the European Congress on Obesity (ECO 2026) in Istanbul, Turkey, indicates that rapid weight loss (RWL) is considerably more effective than gradual weight loss (GWL), both in the amount of weight people lose and in how well that loss is sustained at one year.
For years, conventional thinking has held that rapid weight loss is unhealthy and that shedding weight very quickly raises the chance of regaining it. Yet these concerns rest largely on observational data, historical assumptions, or small studies with methodological limitations. The scientific evidence directly supporting them is limited and inconsistent, and high-quality randomised controlled trial evidence remains relatively sparse.
The study was led by Dr Line Kristin Johnson of the Department of Endocrinology, Obesity and Nutrition at Vestfold Hospital Trust in Tønsberg, Norway, together with colleagues. The centre is a collaborating centre with the European Association for the Study of Obesity (EASO-COM-Centre); EASO leads obesity advocacy and education across Europe and organises ECO.
Setting the treatment targets
A recent large, population-based cohort study concluded that, after weight loss, a body-mass index (BMI) of 27 kg/m² or below and a waist-to-height ratio (WHtR) of 0.53 or below may represent clinically meaningful treatment targets for lowering the 10-year risk of obesity-related complications, namely type 2 diabetes, hypertension, atherosclerotic cardiovascular disease, and hip and knee osteoarthritis.
In this new study, the researchers set out to compare how effectively a rapid weight loss programme and a gradual weight loss programme helped people reach those targets.
How the trial was designed
The 52-week, investigator-initiated, randomised clinical trial was run as a collaboration between the Department of Endocrinology, Obesity and Nutrition at Vestfold Hospital Trust and Roede AS, one of Norway’s leading and most established providers of commercial weight loss programmes.
In total, 284 adults living with obesity (BMI of 30 or above), of whom 257 (90%) were women, were randomised on a one-to-one basis to one of two 16-week, food-based programmes. The rapid weight loss programme reduced energy intake in stages: under 1,000 kcal per day in weeks 1 to 8, under 1,300 kcal per day in weeks 9 to 12, and under 1,500 kcal per day in weeks 13 to 16. The gradual weight loss programme set intake at 800 to 1,000 kcal per day below each participant’s estimated total energy expenditure, with a mean self-reported intake in this group of roughly 1,400 kcal per day.
Estimated energy expenditure was calculated from each participant’s estimated resting energy expenditure and then adjusted according to whether they had low, medium, or high physical activity.
The food composition in both programmes followed current Norwegian dietary recommendations from the Norwegian Directorate of Health. Core advice included eating healthy foods such as vegetables, fruits, whole grains, low-fat dairy products, fish, eggs, lean meat, and other protein-rich foods, while limiting saturated fats and added sugars.
Maintaining the results
After the initial weight loss phase, participants in both groups moved into an identical 36-week weight-regain prevention programme.
Throughout the study, the interventions included weekly in-person group sessions from week 1 to week 16. After that, in-person group meetings took place every 14 days for the first three months, followed by monthly meetings or individual contact via webinars, video, or telephone for the remaining five months.
In these sessions, participants were advised to raise their daily energy intake by 100 to 300 kcal during the first month, until their weight stabilised. From then on, daily intake was adjusted as needed in response to any weight changes across the eight-month maintenance phase. Participants could decide for themselves whether to maintain their weight or aim for further loss, and the majority chose to keep losing weight after the initial 16-week period.
What the trial found
Of the 284 participants, 142 were randomised to the rapid weight loss programme and 142 to the gradual weight loss programme. At baseline, the rapid weight loss group had a mean age of 48.5 years, body weight of 102.4 kg, height of 169 cm, BMI of 35.8 kg/m², waist circumference of 112.5 cm, and WHtR of 0.67. The corresponding figures in the gradual weight loss group were 47.7 years, 103.0 kg, 168 cm, 36.5 kg/m², 112.8 cm, and 0.67.
The primary outcome was one-year percentage total body weight loss (%TBWL). The proportion of participants reaching a BMI of 27 kg/m² or below, or a WHtR of 0.53 or below, after one year were exploratory outcomes.
During the first 16 weeks, the rapid weight loss group lost significantly more weight than the gradual weight loss group, with a mean %TBWL of -12.9% compared with -8.1%, a between-group difference of -4.8%.
At one year, that significant difference was maintained: the mean %TBWL was -14.4% in the rapid weight loss group and -10.5% in the gradual weight loss group, a between-group difference of -3.9 percentage points.
The share of participants achieving a BMI of 27 kg/m² or below was significantly higher in the rapid weight loss group than in the gradual weight loss group at both 16 weeks (13.8% versus 0.8%) and one year (28.3% versus 9.7%). A higher proportion also reached a WHtR of 0.53 or below in the rapid weight loss group, both at 16 weeks (24.2% versus 8.9%) and at one year (33.0% versus 18.4%).
What the researchers say
The authors conclude, “Among adults with obesity, participation in a structured rapid weight loss program resulted in significantly greater weight loss at one year, and higher rates of achieving clinically meaningful BMI and WHtR targets compared with a gradual weight loss approach.
“These findings indicate that, when provided within a controlled and professionally supervised setting, rapid weight loss may represent a more effective method than gradual weight loss for reaching key body weight targets associated with reduced obesity-related health risks.”
Dr Johnson adds, “Our results clearly challenge the prevailing belief that slow and steady gradual weight loss is necessary to prevent weight regain and reduce obesity-related complications.
“By contrast, we show that rapid weight loss is not associated with weight regain, and, more importantly, that a larger proportion of participants undergoing rapid weight loss – compared with gradual weight loss – achieved clinically meaningful treatment targets for reducing the 10-year risk of type 2 diabetes, hypertension, atherosclerotic cardiovascular disease, and hip/knee osteoarthritis.
“These findings are particularly relevant given the urgent need for effective weight-loss and weight-maintenance strategies. As many individuals with obesity cannot access or afford medical or surgical treatments, our results support the potential of effective, commercially available weight-reduction programs to help reduce the growing burden on public health care systems.”
Why it matters
With obesity placing a rising strain on health systems, and with medical and surgical treatments out of reach for many, the trial points to professionally supervised commercial programmes as a potential route to meaningful, lasting results. Its central message reframes a long-standing assumption: under proper supervision, losing weight quickly did not undermine maintenance, and it helped more people reach the targets tied to lower long-term health risks.
CCH insights:
These are impressive results for a diet and lifestyle intervention, with both groups achieving greater than 10% total body weight loss over a period of a year. However, participants received fairly intensive support throughout the entire year of the trial. The important thing is what happens in the next 12 months, after the intervention has stopped – are they able to sustain behavioural changes and weight loss without the support from the programme?
Source: Medical Xpress
Read More
Obesity Leaves a Lasting Imprint on the Immune System, Study Finds
Key Takeaways:
- Immune cells in people living with obesity can retain a long-term “memory” of excess weight through epigenetic changes
- This “obesity memory” may persist for 5–10 years after weight loss and could prolong disease risk
- Sustained weight management may gradually reverse these effects, with potential for targeted therapies to accelerate the process
A long-term immune memory of obesity
People living with obesity may carry a lasting biological imprint of excess weight within their immune system, even after successful weight loss. A 10-year study published in EMBO Reports suggests that key immune cells retain a “memory” of obesity, potentially extending the risk of related health conditions for years.
The research, led by Professor Claudio Mauro at the University of Birmingham and supported by the National Institute for Health and Care Research Biomedical Research Centre in Birmingham, focused on helper T cells, also known as CD4+ lymphocytes. These cells play a central role in coordinating immune responses.
The findings indicate that these immune cells undergo lasting changes that continue to influence how the body regulates inflammation and maintains immune balance long after weight has been reduced.
DNA methylation and the “tagging” process
At the centre of this phenomenon is DNA methylation, a biological process in which chemical markers attach to DNA and alter gene activity without changing the underlying genetic code.
In people living with obesity, this “tagging” process appears to leave a durable imprint on helper T cells. These markers can persist for an extended period, with the study suggesting a timeframe of approximately 5–10 years after weight loss.
This sustained epigenetic modification may disrupt normal immune functions, including the removal of cellular waste and the regulation of immune ageing.
As a result, even individuals who return to a clinically healthy weight may continue to experience altered immune function for several years.
Implications for long-term disease risk
The persistence of this immune “memory” may help explain why the risk of certain conditions associated with obesity does not immediately resolve following weight loss.
Professor Claudio Mauro, co-lead author of the study, explained:
“The findings suggest that short-term weight loss may not immediately reduce the risk of some disease conditions associated with obesity, including type 2 diabetes and some cancers.”
He added:
“Instead, ongoing weight management following loss will see the ‘obesity memory’ slowly fade. This may take several years of sustained weight loss maintenance, likely 5–10 years, though this requires further study, to fully reverse the effects of obesity on T cells.”
The study highlights that long-term weight maintenance, rather than short-term weight loss alone, may be critical for reducing risk over time.
Study design and participant groups
To build a comprehensive understanding of how obesity affects immune cells, researchers analysed samples from multiple human cohorts and experimental models.
These included:
- Blood samples from people living with obesity who received weight loss injections
- Individuals with Alström Syndrome, a rare genetic condition characterised by early-onset childhood obesity, alongside matched healthy controls
- Participants undergoing a 10-week exercise intervention, with blood and fat tissue collected
- People with either a healthy weight or obesity undergoing hip or knee replacement surgery due to osteoarthritis
In addition, the team examined:
- Mouse models fed a high-fat diet
- Blood samples from healthy human volunteers
These diverse data sources enabled researchers to investigate both real-world and mechanistic aspects of immune dysregulation in obesity.
Disrupted cellular processes: autophagy and immune ageing
The study identified two key biological pathways affected by obesity-related DNA tagging:
Autophagy
Autophagy is a cellular “clean-up” process in which cells break down and recycle damaged components. The obesity-related epigenetic changes appear to impair this process, potentially leading to an accumulation of cellular waste.
Immune senescence
Immune senescence refers to the ageing of the immune system. The research suggests that obesity-associated changes may accelerate or dysregulate this process, altering how immune cells respond over time.
Together, these disruptions may contribute to prolonged inflammation and impaired immune function.
Potential for targeted therapies
Beyond identifying the problem, the research also points towards potential therapeutic strategies.
Professor Mauro noted:
“Additionally, our study suggests potential therapeutic opportunities to expedite this process, such as repurposing drugs like SGLT2 inhibitors, which have shown promise in reducing inflammation and promoting immune-mediated clearance of senescent cells in obesity.”
Such approaches could complement existing weight loss interventions by addressing the underlying immune alterations that persist after weight reduction.
A molecular record of metabolic history
Dr Belinda Nedjai, senior author from the Wolfson Institute of Population Health at Queen Mary University London, emphasised the broader significance of the findings:
“Our findings show that obesity is associated with durable epigenetic modifications that influence immune cell behaviour. This suggests that the immune system retains a molecular record of past metabolic exposures, which may have implications for long-term disease risk and recovery.”
This concept of a “molecular record” reinforces the idea that the body’s response to obesity is not easily reversed, even when weight is reduced.
Understanding obesity as a chronic disease
Professor Andy Hogan of Maynooth University highlighted how these findings align with the understanding of obesity as a chronic condition:
“We know obesity is a chronic progressive and relapsing disease and our findings provide further understanding of exactly what are the molecular mechanisms potentially driving the risk of relapsing and highlight the challenges facing people living with obesity to successfully manage their weight.”
The research underscores the biological complexity of obesity and the challenges individuals face in achieving and maintaining long-term health improvements.
Looking ahead
Delivered through the NIHR Biomedical Research Centre in Birmingham, this study contributes to a growing body of evidence that obesity leaves lasting effects on the body at a molecular level.
Future research will aim to refine understanding of how these epigenetic changes can be reversed and how targeted treatments might accelerate recovery of normal immune function.
In the meantime, the findings highlight the importance of sustained weight management and long-term support for people living with obesity, rather than a sole focus on short-term weight loss.
Helping patients hold on to those gains over the long term – and navigate the setbacks a relapsing condition brings – is the focus of professional training such as the College of Contemporary Health’s Behaviour Change Skills: Applying CBT in Practice, a CPD-accredited online short course.
CCH insights:
This study provides further support for the characterisation of obesity as a chronic relapsing disease. Clinically significant weight loss is just the first step in obesity treatment – the challenge is to then maintain the weight loss so that health improvements are sustained, despite the biological memory of obesity promoting weight regain. Whether this memory reduces over time will have major implications for long-term obesity care in the future will have major implications for long-term obesity care in the future. Because sustaining weight loss is where obesity care so often succeeds or fails, CCH’s Behaviour Change Skills: Applying CBT in Practice CPD short course (2 CPD hours, fully online, CPD-accredited) equips healthcare professionals with cognitive and behavioural techniques to help patients maintain progress, handle setbacks and make change stick.
Explore Behaviour Change Skills: Applying CBT in Practice →
Source: University of Birmingham
Dual Burden of Alcohol Use and Obesity Linked to Rising Liver Disease Risk
Key Takeaways:
- Around 1 in 10 U.S. adults report both heavy drinking and obesity, creating a compounded risk for liver disease
- This overlap is most common in younger and middle-aged adults, suggesting risk accumulates early in life
- Integrated, non-judgemental care targeting both conditions together may improve long-term outcomes and reduce progression to advanced liver disease
A growing overlap with serious implications
Heavy alcohol use and obesity are both increasing in the United States, and they are increasingly affecting the same individuals. A new study published in JAMA Internal Medicine explores how often these two major risk factors coincide among U.S. adults and why this overlap has important implications for clinical care and public health policy.
The research was led by Dr Bryant Shuey, a board-certified general internist at UPMC and a clinician-investigator at the University of Pittsburgh Center for Research on Health Care. His work focuses on substance use, chronic disease, and access to care. Drawing on national survey data, the study highlights a critical, and often overlooked, opportunity to intervene earlier in the disease trajectory before severe liver damage develops.
Why examine alcohol use and obesity together?
Dr Shuey explains that this combined risk is increasingly visible in clinical practice:
“In my clinical work, I’ve been seeing more people in their 30s and 40s coming to the hospital with advanced liver disease linked to both alcohol use and metabolic risk factors. Nationally, heavy drinking and obesity are both becoming more common and there has been greater recognition that alcohol and metabolic disease can combine to accelerate liver disease progression. Treatment of both conditions, especially alcohol use disorder, is also lagging, as evident by research by my colleague and study co-author Dr. Eden Bernstein from the University of Colorado. Together, we sought to understand how often risky alcohol use and obesity overlap and what it might mean for prevention and earlier intervention.”
This convergence of risks reflects a broader shift in how liver disease is understood. Rather than being driven by a single cause, many people now present with multiple interacting factors that amplify disease progression.
A significant and early-emerging risk
The study’s central finding is clear:
“The key finding is that about 1 in 10 U.S. adults reported both heavy drinking and a body mass index of 30 or greater in 2023. That’s a substantial share of the population, especially considering how strongly each of these factors contributes to liver disease risk on its own.”
What is particularly striking is how early this overlap appears.
“What stood out most was how early this overlap appears. Rates were highest among young and middle-aged adults, when risk factors for serious liver disease are just beginning to build. These findings suggest that many people are entering adulthood with multiple, reinforcing risk factors for liver disease long before they ever develop symptoms.”
This suggests that prevention efforts may need to begin far earlier than is currently typical, focusing on identifying and addressing risk factors before clinical disease becomes apparent.
How liver disease presents in clinical practice
People living with alcohol-related and metabolically related liver disease may present at very different stages. Some are identified early through routine primary care assessments, while others present later with advanced complications.
Dr Shuey describes this spectrum:
“Patients can show up at different points along the disease course. Some are identified early by their primary care doctor by discussing risk factors like alcohol use and metabolic health and ordering blood work and liver imaging. Others present later, sometimes to the emergency department, with symptoms of advanced liver disease, or cirrhosis, like jaundice, abdominal swelling or gastrointestinal bleeding. Liver disease can lurk for years with no symptoms, so for some, that’s the first time they’re learning they have liver disease. Whether the illness is driven mainly by metabolic disease, alcohol use or a combination of both, if unchecked, the outcome can be the same: progressive liver damage that can lead to cirrhosis and liver failure. That’s why it’s so important to address these risk factors together, not in isolation.”
The silent progression of liver disease underscores the importance of proactive screening and early intervention.
Rethinking care: addressing both risks together
For clinicians, the findings point to the need for a more integrated approach to care.
“We need to routinely screen for both conditions in an empathetic and non-judgmental way and recognize how strongly they interact when it comes to liver disease risk. Clinicians should offer standard evidence-based options to treat both conditions: dietary counseling, motivational interviewing, medications for alcohol use disorder and therapies for metabolic disease such as GLP-1s and related weight loss drugs. There’s growing interest in these medications because they help people reduce their metabolic risk through weight loss and reversing inflammation in metabolic liver disease. Additionally, a smaller trial last year found that GLP-1s may reduce alcohol use among people with alcohol use disorder. While these results should not be overstated, GLP-1s may emerge as an important dual-therapeutic for patients with risky alcohol use and obesity if these findings hold up in larger trials. Ultimately, addressing both risk factors together may be an important strategy to change long-term outcomes.”
This reflects a shift towards dual-risk management, where treatment strategies are designed to address interconnected drivers of disease rather than isolated conditions.
Supporting people without judgement
A central theme in managing these conditions is the importance of person-centred care.
“The most important thing is creating space to talk about these concerns without judgment. I would want to learn about their goals, explore their understanding of the health impacts of alcohol use and metabolic disease, counsel them on treatment options and support them in their decision. For some people, the priority is avoiding serious illness down the road. Others may want to lose weight, drink less or stop drinking altogether. While addressing both conditions simultaneously may be of interest to some patients, others may feel overwhelmed and want to focus on just one. There isn’t a single right goal.”
This highlights the need for flexibility in care plans and respect for individual priorities and readiness for change.
Barriers to care and policy implications
The study also draws attention to wider structural barriers that influence health outcomes.
“Our social conditions shape our health. Improving access to affordable, healthy foods and safe spaces for exercise and activity can go a long way in helping people attain their highest level of health. Bolstering public health messaging about the lesser-known risk of liver disease as a complication of alcohol use and metabolic disease is also critical to helping people make informed decisions. Furthermore, stigma around both weight and alcohol use can discourage people from seeking care in the first place. Fewer than 10% of people with an alcohol use disorder receive treatment, and just 5% are prescribed evidence-based medications that have been demonstrated to reduce alcohol use. Clinicians can be a part of the solution by ensuring they are offering patients standard treatments for alcohol use disorder.”
Access to care remains a major challenge, particularly for those without adequate insurance or financial resources.
“Health care affordability and access to care are major barriers to timely diagnosis and treatment of alcohol- and metabolic-related health issues, particularly for people who are uninsured. Preventing progression to advanced liver disease isn’t just better for patients, it’s far less expensive than treating cirrhosis and its complications. In the U.S., we spend an estimated $135 billion on liver disease every year. We need prevention-focused approaches and more equitable access to care for the populations at highest risk.”
These findings reinforce the importance of prevention-focused policy and equitable healthcare access.
Priorities for future research
Looking ahead, the study highlights several important areas for further investigation.
“We should figure out how to intervene earlier, when obesity and risky alcohol use first begin to overlap, long before advanced liver disease develops. We also need more data on how existing treatments work in patients with multiple, co-occurring risk factors, since many clinical trials have historically excluded these groups.”
There is also a need to better understand how health systems and policy decisions shape outcomes.
“From a policy standpoint, future research should also look at how insurance coverage and access barriers affect outcomes for people at greatest risk. Better evidence in these areas could help guide more effective and equitable prevention strategies.”
A shift towards earlier, integrated prevention
Taken together, the findings point to a clear conclusion: the intersection of heavy alcohol use and obesity represents a growing and under-recognised driver of liver disease. Identifying and addressing these risks earlier, and in combination, may offer a meaningful opportunity to improve patient outcomes and reduce the long-term burden on healthcare systems.
Source: UPMC Life Changing Medicine
Automated Weight Loss Programme Shows Promise for People Living with Cancer in Landmark Trial
Key Takeaways:
- A fully automated, web-based programme delivered clinically meaningful weight loss in people living with and beyond cancer, without any in-person support
- More than 43 percent of participants achieved at least 3 percent weight loss, with nearly one in three reaching 5 percent or more
- The intervention also improved a range of health outcomes, including diet quality, physical functioning, and cardiometabolic markers
A new model for post-cancer care
A large national randomised clinical trial has demonstrated that a fully automated, web-based weight loss intervention can deliver substantial health benefits for people living with and beyond cancer. The programme, developed by researchers at the University of Alabama at Birmingham, represents a significant shift in how post-cancer care may be delivered in the future.
Published in the Journal of the National Comprehensive Cancer Network, the study reported the highest level of weight loss ever achieved through a fully automated intervention in this population. The programme, known as the AMPLIFY Diet (AiM, PLan and act on LIFestYles), was designed to provide structured, evidence-based lifestyle support without requiring direct clinician involvement.
Addressing a major unmet need
A substantial proportion of people living with and beyond cancer are also living with overweight or obesity. In the United States, this figure is estimated to be around 70 percent. This places individuals at increased risk of cardiovascular disease, type 2 diabetes, functional decline, cancer recurrence, and the development of second primary cancers.
Despite this, access to specialist oncology dietitians remains limited. Traditional weight management programmes often rely on in-person consultations or regular coaching, which can be difficult to scale and may not be accessible to all patients.
The AMPLIFY Diet intervention was developed specifically to address these barriers by delivering personalised nutrition and behavioural support entirely online.
A fully automated intervention
The programme operates without live coaching, counselling calls, or face-to-face appointments. Instead, it uses a structured digital platform that includes weekly interactive sessions, goal-setting tools, progress monitoring, and automated personalised feedback.
Participants engage with the system independently, receiving guidance that is grounded in established behavioural and nutritional science. This approach allows for scalability while maintaining a consistent standard of care.
“This is a game changer for cancer survivorship care,” said Wendy Demark-Wahnefried, Ph.D., R.D., senior author and professor at UAB’s School of Health Professions and O’Neal Comprehensive Cancer Center. “We showed that a completely automated online program grounded in decades of behavioral and nutrition science can safely and effectively help cancer survivors lose weight and improve their health at scale.”
Study design and participant profile
Between 2020 and 2024, the study enrolled 349 participants aged between 50 and 82 years from 31 states across the United States. All participants were living with and beyond cancers associated with obesity.
The cohort included individuals with a range of cancer types, including breast, colorectal, prostate, endometrial, ovarian, thyroid, renal, and haematologic cancers. Participants were randomly assigned to either the AMPLIFY Diet programme or a control group receiving standard survivorship information.
Clinically meaningful weight loss outcomes
After six months, the results showed clear differences between the intervention and control groups.
More than 43 percent of participants in the AMPLIFY Diet group achieved weight loss of at least 3 percent of their body weight. In comparison, only 13 percent of those receiving usual care reached this threshold.
In addition, nearly one in three participants in the intervention group lost at least 5 percent of their body weight. This level of weight loss is widely associated with reductions in cardiovascular risk and improvements in cancer-related outcomes.
On average, weight loss in the intervention group was nearly five times greater than that observed in the control group.
Broader health improvements
The benefits of the programme extended beyond weight loss alone. Participants in the AMPLIFY Diet group experienced improvements across multiple domains of health and wellbeing.
These included reductions in waist circumference and overall caloric intake, as well as improvements in diet quality. Biochemical markers also shifted in a favourable direction, with lower circulating levels of leptin, a hormone associated with cancer progression and cardiometabolic disease.
Further gains were observed in blood pressure, physical functioning, and cognitive performance. Participants also reported improvements in depression and their ability to engage in social roles, suggesting a broader impact on quality of life.
Strong engagement without human support
One notable finding from the study was the level of participant engagement. Individuals completed an average of 60 percent of the weekly sessions, which is considerably higher than engagement rates typically reported in other digital lifestyle interventions.
This suggests that a well-designed automated system can maintain user engagement even in the absence of direct human interaction.
Implications for scalable care
Unlike many conventional weight management programmes, the AMPLIFY Diet intervention does not require ongoing staff involvement. This makes it particularly well suited for integration into healthcare systems, cancer centres, and community-based services.
The ability to deliver consistent, evidence-based care at scale may help address longstanding gaps in survivorship support, particularly in settings where specialist resources are limited.
The role of behavioural and nutritional care
The researchers emphasise that lifestyle-based interventions remain a cornerstone of care for people living with and beyond cancer, particularly as pharmacological approaches continue to evolve.
“Behavioral and nutritional interventions are essential,” Demark-Wahnefried said. “Diet quality, muscle preservation, cognition, and long-term sustainability of a healthful lifestyle and body weight are critical for cancer survivors, and even if weight loss medications eventually receive broadscale endorsement, they alone do not address all of these needs.”
Future directions
The research team is now focusing on expanding the reach of the AMPLIFY Diet programme across both clinical and non-clinical settings. The aim is to improve access to effective survivorship care while also contributing to broader cancer prevention efforts.
The study was funded by the National Institutes of Health and the American Cancer Society.
Read More
Whole Milk and Childhood Obesity – New Study Challenges Long-Standing Dietary Advice
Key Takeaways:
- Children who consumed whole-fat milk in early childhood showed lower odds of living with obesity in later childhood compared with those consuming reduced-fat options
- The study found no evidence that whole milk increases adiposity, challenging decades of low-fat dietary guidance
- Researchers suggest milk fat may influence satiety and overall dietary patterns, although mechanisms remain unclear
Rethinking milk fat and childhood health
New research from the University of Toronto suggests that children who consume whole-fat milk during early childhood may have a lower likelihood of living with obesity in middle childhood than those who drink reduced-fat milk.
These findings contribute to a growing body of evidence indicating that lower-fat milk may not provide the protective effect against childhood obesity that has long been assumed. For several decades, dietary guidelines in many countries have promoted low-fat dairy products. For example, Canada’s Dietary Guidelines in 2019 continued to recommend reduced-fat options, reflecting a broader historical focus on reducing dietary fat intake.
Study overview and design
The study, published in the American Journal of Clinical Nutrition, is described as one of the most comprehensive analyses to date examining the relationship between milk consumption and childhood obesity over time.
Researchers, including former postdoctoral fellow Tara Zeitoun and doctoral student Zheng Hao Chen, analysed data from the CHILD Cohort Study. This large, prospective study tracks health data from thousands of children from before birth through to adolescence.
Caregivers reported the type of milk consumed by children, including skim, one per cent, two per cent, and whole-fat milk. Researchers then assessed a range of outcomes at ages five and eight, including:
- Body mass index (BMI)
- Waist-to-height ratio
- Fat mass
- Preclinical and clinical obesity status
Key findings
Milk consumption was common among participants, with over 90 per cent of children consuming milk before the age of five. Among these:
- 24 per cent consumed whole-fat milk
- Approximately half consumed less than one cup per day
Despite relatively modest intake, notable differences emerged. Children who consumed whole milk at age five had significantly lower BMI at age eight. They also had 69 per cent lower odds of living with obesity compared with children who consumed skim milk.
In addition, researchers identified a broader pattern in which higher milk fat content was associated with more favourable adiposity profiles.
Expert insight
Kozeta Miliku, a professor of nutritional sciences at the University of Toronto’s Temerty Faculty of Medicine and a researcher at the Joannah and Brian Lawson Centre for Child Nutrition, emphasised the implications of these findings:
“The most important learning from this study is that whole milk was not associated with higher adiposity or obesity risks risk in children, and may even be linked to healthier growth patterns,”
She also highlighted the limitations of focusing narrowly on fat reduction:
“Switching to lower-fat milk has been about cutting fat in the diet, but that may miss the bigger picture,” says Miliku. “When we think about healthy growth, it’s important to consider the overall nutritional context. Removing fat does not automatically make skim milk a healthier choice for children.”
Implications for public health guidance
The findings raise important questions about long-standing public health recommendations. Prior to 2019, Health Canada advised that children transition from whole milk to reduced-fat milk from the age of two. Similarly, the Dietary Guidelines for Americans 2020–2025 supported reduced-fat dairy intake.
However, recent policy developments suggest a shift in thinking. In the United States, the Whole Milk for Healthy Kids Act has allowed full-fat milk to be reintroduced into school lunches, aligning with updated national guidance that is more permissive of full-fat dairy.
Possible biological mechanisms
While the study did not directly investigate underlying mechanisms, the researchers proposed several hypotheses:
- Milk fat may enhance satiety, potentially reducing the consumption of energy-dense, nutrient-poor foods
- It may influence overall energy balance
- It could play a role in metabolic pathways linked to growth and nutritional status
These potential explanations highlight the complexity of dietary patterns and suggest that focusing on single nutrients may overlook broader physiological effects.
The need for further research
Miliku noted that additional research is needed to better understand how milk fat may influence obesity risk and whether any protective effects persist into adolescence and adulthood.
With Canada’s 2019 dietary recommendations offering limited specific guidance on milk consumption for children, the study’s findings may help inform future discussions among parents, clinicians, and policymakers.
A broader view of healthy diets
Miliku concluded by reinforcing the importance of overall dietary quality:
“Whole fat milk can be part of a healthy diet and does not on its own increase obesity risk,” she adds. “And it’s important to think about the overall quality of the diet – the fruits and vegetables, whole grains and protein-rich foods they consume.”
Funding and support
The research was funded by the Canadian Institutes of Health Research and the Joannah & Brian Lawson Centre for Child Nutrition at the University of Toronto, supported through a donation by President’s Choice Children’s Charity.
CCH insights:
This interesting new research will hopefully be the trigger for governments and public health bodies to review and amend their outdated advice to choose low-fat dairy options instead of full-fat. The reductionist approach to nutrition, which considers food just in terms of calories and individual nutrients, is an oversimplification which does not help our understanding of the relationship between food and health. If the best food for children early in life is whole milk, why would it be beneficial for them to suddenly switch to low-fat milk at the age of 2?
Read More