Obesity Care

Epigenetic changes in fat cells shed light on why weight loss is hard to sustain

Even after significant weight loss, fat cells retain a ‘memory’ of obesity, according to groundbreaking research published in Nature. This discovery sheds light on why maintaining weight loss can be so challenging, underscoring the need for long-term support for individuals who achieve significant weight reductions.

The Epigenetic Memory of Obesity

The study reveals that obesity triggers changes in the epigenome—chemical modifications to DNA and proteins that regulate gene activity. These epigenetic alterations disrupt the normal functioning of fat cells, impairing their ability to operate as they would in a body without obesity. Crucially, these changes persist even after weight loss brings body weight to a healthy level.

This persistence highlights the complexity of obesity as a condition, suggesting that maintaining weight loss often requires more than personal effort. Co-author Laura Hinte, a biologist at ETH Zurich, explained that the findings emphasise the need for additional support. “It means that you need more help, potentially,” she said, adding that this reinforces the idea that “it’s not your fault.” By uncovering the molecular underpinnings of this phenomenon, the study offers an explanation for the enduring challenges many individuals face after weight loss.

Exploring the Molecular Mechanisms

To investigate why weight is often regained after loss, researchers examined fat tissue from individuals with severe obesity and compared it to fat tissue from people who had never experienced obesity. They discovered significant differences in gene activity: some genes were more active in the fat cells of individuals with obesity, while others were less active.

Even after weight-loss surgery, the genetic activity in fat cells from participants with a history of obesity remained altered. Two years post-surgery, despite substantial weight reductions, the fat cells still displayed an obesity-linked pattern. Similar results were observed in mice, further supporting the findings.

The Lasting Impact of Obesity on Fat Cells

The research pinpointed specific genes that were affected by obesity. Genes that promote inflammation and fibrosis (the formation of stiff, scar-like tissue) were dialled up, while those essential for normal fat cell function were suppressed. These changes were traced to alterations in the epigenome, which dictate whether specific genes are switched on or off.

The durability of this ‘memory’ was tested by placing mice with obesity on a diet. Despite becoming lean again, their fat cells continued to exhibit obesity-related epigenetic changes months later. Co-author Ferdinand von Meyenn, an epigenome specialist at ETH Zurich, noted that while it is unclear how long the body retains this memory, “there may be a time window when this memory will be lost,” although “we don’t know” for certain. This lingering effect demonstrates how deeply obesity can alter the body at the cellular level.

Effects of Fat Cell Memory on Metabolism

The persistent memory of obesity has profound implications for metabolism. Fat cells from mice formerly with obesity absorbed more sugar and fat than those from control mice that had never had obesity. Moreover, when placed on a high-fat diet, the mice formerly with obesity regained weight more quickly than their counterparts who had never had obesity.

While these findings are striking, the study stops short of proving a direct causal link between epigenetic changes and altered fat cell function. Scientists such as Evan Rosen, a biologist at Beth Israel Deaconess Medical Center in Boston, pointed out that although the research provides a valuable list of epigenetic alterations, determining which changes drive the fat cells’ lingering memory will be challenging. Von Meyenn acknowledged this limitation, stating that “it’s not yet a causal link,” but rather “correlation” that his team continues to explore.

Implications for Weight Loss and Obesity Stigma

The study’s findings have broader implications for addressing obesity-related stigma. They suggest that the biological changes caused by obesity create long-term challenges that cannot simply be overcome with willpower alone. Von Meyenn stressed the importance of preventing obesity in the first place, explaining that while people who lose weight can remain lean, “it will require a lot of effort and energy to do that.”

By uncovering the epigenetic mechanisms that underlie obesity and its lingering effects, the research may pave the way for improved treatments and support systems. This, in turn, could help reduce stigma and foster greater understanding of the biological challenges faced by individuals seeking to manage their weight long-term.

Stress hormones may be the key to understanding how obesity causes diabetes, researchers reveal

A groundbreaking study from Rutgers Health, in collaboration with several institutions, suggests that stress hormones, rather than impaired cellular insulin signalling, might be the primary cause of obesity-related diabetes. This research, published in Cell Metabolism, challenges the traditional view of how obesity-induced insulin resistance develops and introduces novel perspectives on potential treatment approaches.

“We have been interested in the basic mechanisms of how obesity induces diabetes. Given that the cost of the diabetes epidemic in the U.S. alone exceeds $300 billion per year, this is a critically important question,” said Christoph Buettner, chief of endocrinology, metabolism, and nutrition at Rutgers Robert Wood Johnson Medical School and the senior author of the study.

Challenging Long-Standing Beliefs About Obesity and Diabetes

Historically, scientists have attributed the development of diabetes in people with obesity to disrupted insulin signalling within liver and fat cells. However, this new study offers an alternative explanation, highlighting the role of the body’s sympathetic nervous system (SNS) – commonly associated with the “fight or flight” response. According to the researchers, overeating and obesity stimulate this system, leading to increased levels of the stress hormones norepinephrine and epinephrine, which seem to interfere with insulin’s effects. Importantly, they observed that this interference occurs even when cellular insulin signalling remains intact.

Through experiments on mice, the researchers found that overeating rapidly increases the stress hormone norepinephrine within days, indicating just how quickly excess food can stimulate the SNS.

The Role of Stress Hormones in Disease Development

To better understand how this hormone surge influences disease progression, the researchers used a new type of genetically engineered mice that are identical to regular mice except for one critical difference: they are unable to produce catecholamines, the primary stress hormones, outside their brain and central nervous system.

The study showed that when these genetically modified mice were fed an obesity-inducing, high-fat and high-sugar diet, they gained just as much weight as their regular counterparts. Yet, they did not develop metabolic diseases typically associated with obesity.

“We were delighted to see that our mice ate as much because it indicates that the differences in insulin sensitivity and their lack of metabolic disease are not due to reduced food intake or reduced obesity but due to the greatly reduced stress hormones. These mice cannot increase stress hormones that counteract insulin; hence, insulin resistance does not develop during obesity development.”

Explaining the Variation in Diabetes Development

The findings may provide insight into why some people living with obesity develop diabetes while others do not, and why stressful conditions can worsen diabetes, even without significant weight gain. Buettner noted: “Many types of stress – financial stress, marital stress, the stress associated with living in dangerous areas or suffering discrimination or even the physical stress that comes from excessive alcohol consumption — all increase diabetes and synergize with the metabolic stress of obesity.”

He added, “Our finding that even obesity principally induces metabolic disease via increased stress hormones provides new insight into the common basis for all these factors that increase the risk of diabetes. Stress and obesity, in essence, work through the same basic mechanism in causing diabetes, through the actions of stress hormones.”

A Paradigm Shift in Understanding Insulin Resistance

While it has long been recognised that catecholamines can impair insulin action, this study suggests that heightened activity of these stress hormones might be the fundamental driver of insulin resistance in obesity. Stress hormones increase glucose and lipid levels in the bloodstream, while insulin typically works to lower them. The study reveals that insulin signalling remains intact in many cases of insulin resistance associated with obesity. Instead, the heightened presence of stress hormones acts like an “accelerated gas pedal,” pushing blood sugar and fat levels up, despite insulin’s continued attempts to reduce them.

“Some colleagues are at first surprised that insulin resistance can exist even though cellular insulin signalling is intact,” Buettner explained. “But let’s not forget that the gas pedal effects of stress hormones are exerted through very different signalling pathways than insulin signalling. That explains why the ability of insulin to ‘brake’ and reduce the release of sugar and fat into the bloodstream is impaired even though insulin signalling is intact because stress signalling is predominant.”

Potential for New Treatments

These findings open the door to considering medications that reduce catecholamines – encompassing all stress-related hormones produced by the SNS and adrenal glands – as a possible treatment for diabetes. However, medicines currently used to block catecholamines for high blood pressure have not shown significant benefits for diabetes, possibly due to their inability to target the relevant receptors or their complex interactions within the brain and body.

Buettner and Kenichi Sakamoto, the study’s first author and an assistant professor of endocrinology at Robert Wood Johnson Medical School, are now preparing to validate these findings in human studies. They are also exploring the role of the SNS in other forms of diabetes, including Type 1 diabetes. “We would like to study if short-term overfeeding, as some of us experience during the holidays by gaining five to 10 pounds, increases insulin resistance with heightened sympathetic nervous system activation,” Buettner said.

A New Direction for Diabetes and Metabolic Disease Research

Ultimately, this research could lead to a new focus on reducing stress hormones as a therapeutic strategy to tackle insulin resistance, diabetes, and metabolic diseases, shifting away from targeting insulin signalling alone.

“We hope this paper provides a different take on insulin resistance,” Buettner concluded. “It may also explain why none of the drugs currently used to treat insulin resistance, except insulin itself, directly increases cellular insulin signalling.”

By highlighting the potential for stress hormone reduction to prevent or treat diabetes, these findings represent a substantial step forward in understanding and addressing the complex relationship between obesity and diabetes.

Study finds weight-loss surgery in adolescents leads to major long-term health benefits

A landmark study spanning 18 years and costing $29 million has found that weight-loss surgery in adolescents with severe obesity can lead to long-lasting health improvements, particularly in the remission of type 2 diabetes. The research, funded by the National Institutes of Health (NIH) and published in the New England Journal of Medicine, highlights how surgical interventions in young people bring about more sustained benefits compared to adults who undergo the same procedures.

With a rising prevalence of severe obesity in young people, researchers underscore the need to understand the benefits and risks of medical and surgical options. “These findings are essential as effective treatment options for severe paediatric obesity remain rare,” said Dr Thomas Inge, the study’s principal investigator and surgeon-in-chief at Lurie Children’s Hospital in Chicago. “Robust data on the outcomes of modern bariatric procedures are invaluable for clinicians and families considering ways to support adolescents facing obesity, especially in cases of rapid weight gain,” added Dr Inge, who also directs the hospital’s bariatric surgery programme.

The trial, which ran from 2006 to 2012, included approximately 260 adolescents aged 13 to 19, who underwent bariatric surgery at one of five centres in the United States, including Cincinnati Children’s, Texas Children’s Hospital in Houston, Children’s Hospital of Alabama in Birmingham, the University of Pittsburgh Medical Center, and Nationwide Children’s Hospital in Columbus, Ohio.

Adolescents with severe obesity who had bariatric surgery before age 19 experienced sustained weight loss a decade later. Additionally, they showed significant resolution of obesity-related health conditions, including type 2 diabetes, hypertension, and elevated cholesterol. Researchers reported that participants maintained substantial reductions across these conditions, with an average 20% decrease in body mass index (BMI), a 55% reduction in type 2 diabetes, a 57% decrease in hypertension, and a 54% improvement in abnormal cholesterol.

The benefits of surgery appeared similar between those who underwent gastric bypass and those who received sleeve gastrectomy, indicating both procedures are effective in treating obesity-related health issues in young people.

Importantly, the study found that the 55% reduction in type 2 diabetes in adolescents following surgery was far greater than that observed in adults who had undergone the same procedures. Recent NIH-funded studies in adults showed only an 18% decrease in diabetes after seven years and 12.7% after 12 years. Given the rapid progression of type 2 diabetes in young people, this study demonstrates the considerable long-term health benefits of bariatric surgery when undertaken during adolescence.

“This study underscores that surgical treatment should be considered earlier in the course of severe obesity,” Dr Inge remarked. However, he highlighted a critical barrier to access: fewer than 1% of eligible adolescents with severe obesity receive surgery due to parental reservations and other factors. “We should advocate for early intervention and ensure that adolescents have access to effective therapies to mitigate the progression of obesity-related conditions, such as type 2 diabetes and hypertension,” Dr Inge emphasised. In addition to his role at Lurie Children’s Hospital, Dr Inge serves as a professor of surgery and paediatrics at Northwestern University Feinberg School of Medicine in Chicago.

The study has received praise from other experts in adolescent weight management, who recognise the growing importance of effective interventions for severe obesity in young people. “The rate of obesity continues to rise in children, threatening to impact future life expectancy and healthcare costs,” noted Dr Kirk Reichard, surgical director of the bariatric surgery programme at Nemours Children’s Hospital in Wilmington, Delaware. Although not directly involved in the study, Dr Reichard underscored the critical need to address paediatric obesity. “While efforts to address prevention are critical, the reality is that 20% of American children are now affected by obesity and need our help,” said Dr Reichard, who is also a clinical professor of surgery and paediatrics at Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia.

Another expert, Dr Andrea Coviello, an endocrinologist and director of the weight management programme at the University of North Carolina School of Medicine in Chapel Hill, pointed out that long-term data on bariatric surgery in younger patients has been limited. “There has been a lack of long-term data on the benefits and risks of bariatric surgery in younger patients,” Dr Coviello said, adding that “this study helps to fill in knowledge gaps that may help healthcare providers and parents to make informed decisions about healthcare options for children with obesity and obesity-related conditions such as type 2 diabetes.”

Dr Coviello encouraged parents to seek guidance from paediatricians and weight-loss specialists if their children are affected by obesity, particularly if they experience related health issues such as type 2 diabetes or high blood pressure. “Appropriate care and weight loss earlier may significantly improve their child’s health in the longer term,” she noted.

The findings of this study hold significant implications for addressing severe obesity in adolescents, demonstrating that early surgical intervention can lead to sustained health improvements and potentially prevent the worsening of obesity-related conditions later in life.

Surge in endometrial cancer among younger women linked to rising obesity rates

Endometrial cancer, historically more prevalent in post-menopausal women, has seen a significant and concerning rise in cases among women under the age of 40. This trend has puzzled reproductive health experts, prompting urgent research into its causes.

Researchers from UCI Health now report a strong correlation between this surge in endometrial cancer among younger women and the rapidly increasing obesity rates. They argue that this trend demands immediate public health interventions to reverse the alarming trajectory.

Between 2001 and 2018, cases of endometrial adenocarcinoma—the most common form of endometrial cancer—rose by 137% among women aged 20 to 29, and by 71% among those aged 30 to 39, according to data presented at a recent American Society of Clinical Oncology (ASCO) conference. The increases were even more pronounced among younger Black women and Latinas.

Over the same period, obesity rates surged, rising by 7.5% per year among women aged 20 to 29, and by 4.5% annually among those aged 30 to 39, the study revealed.

A Public Health Emergency

“Endometrial cancer is the most common gynaecological cancer encountered in the United States,” notes Dr Krishnansu Tewari, a UCI Health gynaecologic oncologist and co-author of the study.

Once primarily seen in older women, endometrial adenocarcinoma is now the sixth most common cancer in women overall, and it is becoming increasingly deadly. It is projected to cause more than 13,000 deaths this year, up from 3,000 annual deaths in the late 1980s.

“This represents a public health emergency,” states Dr Alex Francoeur, the lead author of the study. Francoeur emphasises the need for a concerted effort to educate women and healthcare providers about the risks posed by obesity in developing endometrial adenocarcinoma.

Analysing Two Decades of Data

The retrospective study analysed data from more than 580,000 cases of endometrial adenocarcinoma in the U.S. over the last two decades. Researchers then compared these findings with data on obesity rates among women over the same period.

The results revealed a particularly strong link between rising obesity rates and increased incidences of cancer in younger women, especially women of colour.

“When examining trends by race and ethnicity, we found that the rate of endometrial cancer in Black women has increased by 25% since 2001, and by 17% in Hispanic women,” says Francoeur, who is a gynaecologic oncology fellow at the UCI School of Medicine’s Department of Obstetrics & Gynaecology.

Although further research is needed to establish a direct causal link, the study’s data strongly suggest the need for targeted public health initiatives aimed at educating women and reducing obesity rates.

Raising Awareness is Key

“Action is needed to address the impact of obesity on endometrial cancer,” Francoeur stresses. She advocates for the following measures:

1. Raising awareness: “Sharing this information with gynaecology patients and providing early education on the risk factors associated with obesity and reproductive health is crucial.”
2. Encouraging weight management: “Discussions about weight should become a routine part of health maintenance, similar to the way cervical cancer screenings and mammography are standard components of preventive care.”

Francoeur highlights that there are many ways for individuals to receive support, including consulting a dietitian, considering medications that target weight loss, and exploring surgical options to manage obesity.

Fertility-Sparing Treatment Options

For individuals of childbearing age diagnosed with endometrial cancer, surgery is not always the only treatment option.

“With early-stage endometrial cancers, we can often manage the disease with hormone therapy, allowing patients to preserve their ability to conceive,” explains Tewari, who is also a professor and chief of the Division of Gynaecologic Oncology in the Department of Obstetrics & Gynaecology.

Progestin therapy, a hormone treatment, can sometimes be used to shrink or eliminate the cancer temporarily in those wishing to maintain fertility. The most commonly used medications in this treatment are:

1. Medroxyprogesterone acetate, administered as an injection or a pill.
2. Megestrol acetate, available as a pill or liquid.

However, Tewari cautions that this approach is not yet a standard treatment and may increase the risk of cancer progression. “It’s vital to confirm the grade of the cancer with a gynaecologic oncologist and a pathologist, and to consult with a fertility specialist before beginning progestin therapy,” he advises.

Study reveals sweet tooth linked to increased risk of depression, diabetes, and stroke

Individuals with a preference for sweet foods and sugary drinks face a significantly higher risk of developing conditions such as depression, diabetes, and stroke, according to groundbreaking research from the University of Surrey. The study, which highlights the complex interplay between dietary habits and long-term health, was recently published in the Journal of Translational Medicine. 

The research team analysed anonymised dietary data from 180,000 volunteers from the UK Biobank, a large-scale biomedical database, and utilised artificial intelligence (AI) to categorise participants into three distinct dietary profiles based on their food preferences:

1. Health-conscious: This group prioritises fruits, vegetables, and plant-based foods, showing a clear preference for healthier options over animal-based or sweet foods.
   
2. Omnivore: These individuals enjoy a balanced variety of foods, including meats, fish, vegetables, and occasional sweets and desserts.
   
3. Sweet tooth: This group has a strong preference for sugary foods and drinks, while showing less interest in healthier options such as fruits and vegetables.
   

To explore how these preferences might impact health, the researchers examined blood samples from participants, measuring 2,923 proteins and 168 metabolites. These biological markers offer insight into how the body processes nutrients and its overall functioning. Proteins, for instance, are crucial for bodily processes such as immune defence, muscle function, and brain activity. Metabolites are small molecules produced during digestion and other metabolic processes, providing a snapshot of the body’s internal health.

By comparing the levels of these proteins and metabolites across the three groups, the researchers uncovered distinct biological differences, offering a deeper understanding of how diet impacts health.

Professor Nophar Geifman, lead author of the study and Professor of Health and Biomedical Informatics at the University of Surrey, explained, “The foods that people like or dislike appear to have a direct link to their health. If someone regularly chooses cakes, sweets, and sugary drinks, our study suggests that this preference may have detrimental effects on their overall well-being.”

The study revealed that individuals in the sweet tooth group were 31% more likely to experience depression. Additionally, they had notably higher rates of diabetes and vascular heart conditions compared to those in the other two groups.

“Importantly, by using data-driven AI methods, we were able to identify these groups based on food preferences, and these groups turned out to be quite meaningful in relation to health outcomes and biological markers,” added Professor Geifman.

Sugar is often an integral part of many people’s diets, and the study reinforces concerns about the widespread consumption of processed sugar. “As a society, we should be more mindful of our food choices. While it is not about dictating what people should eat, our goal is to provide information that helps individuals make informed decisions about their diets,” said Geifman.

In addition to examining proteins and metabolites, the researchers also reviewed standard blood biochemistry tests for participants in each dietary group. The results were concerning for the sweet tooth group, who displayed elevated levels of C-reactive protein, a marker of inflammation, as well as higher glucose levels and poor lipid profiles, which are risk indicators for diabetes and cardiovascular disease.

In contrast, the health-conscious group, which consumed more dietary fibre, exhibited lower risks of heart failure, chronic kidney disease, and stroke. Meanwhile, the omnivore group demonstrated moderate health risks, falling between the other two groups.

Professor Geifman further noted, “In those with a sweet tooth, we found several red flags in their blood tests, including markers for inflammation and poor lipid profiles. These are significant warning signs for serious conditions like diabetes and heart disease.”

The findings add to the growing body of evidence highlighting the negative impact of excessive sugar consumption on health. According to the British Nutrition Foundation, individuals in the UK consume between 9% to 12.5% of their daily calorie intake from “free sugars”—these are sugars added to foods and drinks. Popular sources of free sugars for adults include biscuits, cakes, pastries, and fruit pies, while sugary soft drinks and alcoholic beverages are also major contributors.

This study underscores the urgent need for greater awareness around dietary habits and their long-term implications on mental and physical health. While occasional treats may not seem harmful, consistently choosing sugar-laden foods and drinks could increase the likelihood of developing serious health conditions over time.

As Professor Geifman emphasised, “These findings serve as a reminder that the choices we make about what we eat can have lasting consequences on our health. While no one is saying people should entirely eliminate their favourite foods, moderation and a focus on healthier options could greatly reduce the risk of these debilitating conditions.”

This new research provides a compelling argument for reconsidering dietary habits, particularly for those with a sweet tooth, and for taking proactive steps to improve overall well-being through mindful eating.

Daily Brazil nut consumption may reduce inflammation and support gut health, new study suggests

Brazil nuts are one of the most concentrated sources of selenium, a trace mineral that plays a crucial role in the body’s antioxidant defences, immune response, and thyroid hormone metabolism. Selenium deficiency has been linked to several health issues, including chronic inflammation and impaired gut health.

Low levels of selenium in the bloodstream have been associated with inflammation-related conditions, including gut health challenges. Research has also identified connections between obesity, inflammation, and gut issues such as increased intestinal permeability, commonly known as “leaky gut.” This condition may occur when inflammation and body fat levels rise, causing the tight junctions in the cells lining the intestines to loosen. When these junctions become less effective, antigens, toxins, and bacteria may enter the bloodstream, triggering further inflammation, thus creating a harmful cycle where obesity exacerbates intestinal permeability, and vice versa.

In a recent study, researchers examined the impact of daily consumption of Brazil nuts on inflammation and intestinal permeability, specifically focusing on women living with overweight or obesity, during an 8-week calorie-restricted diet. The study’s findings, published in The Journal of Nutrition, suggest that eating 8 grams of Brazil nuts per day could improve these health markers, likely due to their rich selenium content.

The Brazil nuts used in the study were sourced from Amazonas, Brazil, and donated by ECONUT. However, attempts to contact ECONUT for comment were unsuccessful at the time of publication, and their involvement in the study was not noted as a conflict of interest.

The Study’s Design and Findings

The study was conducted by researchers from the Department of Nutrition and Health at the Universidade Federal de Viçosa in Brazil between June 2019 and September 2021. It involved 56 women aged 20 to 55, with an average age of 34 years. The women were categorised as either living with overweight or obesity, with 17.4% having specific cardiometabolic risk factors and 82.6% living with obesity, regardless of risk factors.

Participants were excluded from the study if they were pregnant, lactating, menopausal, athletes, vegan, had certain medical conditions, were using specific medications, had experienced significant weight changes, regularly consumed nuts, or had other potential study interferences.

The participants were divided into two groups: a control group and a Brazil nut group. Both groups followed a customised menu designed to provide approximately 500 fewer calories than their estimated daily energy requirements. The macronutrient composition of the diet was 50% carbohydrates, 30% fats, and 20% proteins, in line with established obesity management guidelines. Each participant was encouraged to lose at least 4 kilograms over the 8-week period.

To ensure a balanced intake of fats and calories, both groups were provided with controlled-ingredient salad dressings:

• Control group: Followed a nut-free diet and consumed 10 grams of soybean oil-based salad dressing with lemon daily.
• Brazil nut group: Consumed 8 grams of Brazil nuts (providing 347.2 micrograms of selenium) as a morning snack and 5 grams of canola oil-based salad dressing with lemon each day.

Participants received bi-weekly counselling from a nutritionist who monitored their diet adherence, including alcohol consumption. Any participant who failed to adhere to the study protocol was excluded from the final analysis.

Researchers measured inflammatory markers in the blood and selenium levels. Intestinal permeability was assessed using the lactulose/mannitol test (LM ratio), and statistical analyses were conducted to evaluate changes between the groups, with a 97% power to detect differences in intestinal permeability.

Brazil Nuts Associated with Reduced Inflammation and Improved Gut Health

Of the 56 women initially recruited, 46 completed the study. At the start, the control group had a higher intake of polyunsaturated fats compared to the Brazil nut group. During the 8-week intervention, the control group reduced their intake of saturated fats, while the Brazil nut group increased their intake of polyunsaturated fats and dietary fibre.

Both groups achieved similar calorie restrictions and experienced modest weight loss (approximately 3 kilograms) and small reductions in waist circumference. However, the Brazil nut group showed a significant increase in selenium levels, confirming adherence to their Brazil nut consumption.

Compared to the control group, the Brazil nut group exhibited lower levels of inflammatory markers, including C-reactive protein (CRP), tumour necrosis factor (TNF), interleukin-1β (IL-1β), and interleukin-8 (IL-8), indicating a reduction in systemic inflammation. In the Brazil nut group, CRP levels decreased from 7.1 mg/L to 5.6 mg/L over the 8 weeks, while the control group saw an increase in CRP levels from 8.0 to 9.4 mg/L. Although the exact mechanism behind these changes is not fully understood, it is likely linked to improvements in gut inflammation and intestinal permeability.

Women in the Brazil nut group who lost more weight also showed more pronounced reductions in CRP levels. Additionally, this group demonstrated lower lactulose excretion and LM ratio values, which are markers of improved intestinal permeability. However, these changes were not statistically significant when compared to the control group.

Further analysis revealed that higher blood selenium levels were associated with lower levels of IL-1β and IL-8, and changes in IL-8 were related to the LM ratio. These findings suggest that selenium levels may predict improvements in both systemic inflammation and gut permeability.

Study Limitations and Expert Insights

This study had certain limitations, including its small sample size, short duration, and the fact that it only included young to middle-aged women from Brazil. As a result, the findings may not be generalisable to other populations. The participants were also not blinded to their dietary interventions, the study was not randomised, and calorie restriction adherence was primarily self-reported, which may have introduced reporting errors.

Commenting on the study, registered dietitian Alyssa Simpson, RDN, CGN, CLT, who was not involved in the research, highlighted the need for further studies to isolate the effects of selenium from other dietary variables. She stated: “The findings indicate that selenium from Brazil nuts significantly influences inflammation and intestinal permeability, but the simultaneous increases in polyunsaturated fats and fibre intake complicate attributing the effects solely to selenium.”

Simpson suggested that a more controlled study design could help clarify the individual effects of selenium, polyunsaturated fats, and fibre on inflammation and gut health.

Dr. Thomas M. Holland, a physician-scientist from the RUSH Institute for Healthy Aging, added: “In this study, increased selenium levels correlated with reductions in inflammatory cytokines and improvements in intestinal permeability, which may enhance the absorption of nutrients.”

How Many Brazil Nuts Should You Eat Per Day?

Kiran Campbell, RDN, a medical nutrition advisor, explained that the human body cannot produce selenium, making dietary intake essential. While a single Brazil nut provides approximately 96 micrograms of selenium—nearly double the recommended daily intake for most adults—experts recommend consuming just 1–2 Brazil nuts per day to avoid exceeding the safe upper limit of 400 micrograms of selenium per day.

The European Food Safety Authority (EFSA) has set a lower upper limit of 255 micrograms of selenium daily for adult men and women. Consuming too much selenium can lead to toxicity, with symptoms such as brittle nails, hair loss, skin rashes, and neurological issues.

In conclusion, incorporating 1–2 Brazil nuts daily may offer practical and beneficial effects in reducing inflammation and supporting gut health, but they should be consumed as part of a well-rounded, healthy diet.

Endurance exercise transforms fat tissue and improves metabolic health in adults with obesity

A new study published in Nature Metabolism reveals that long-term endurance exercise leads to significant improvements in abdominal subcutaneous adipose tissue (aSAT) in individuals living with obesity. The study, conducted in the United States, aimed to isolate the benefits of exercise from weight loss, showing how regular physical activity improves cardiometabolic health.

The research found that those who exercised regularly had higher capillary density, fewer pro-inflammatory macrophages, and increased levels of proteins involved in angiogenesis, mitochondrial function, and fat storage. These changes suggest improved fat metabolism and enhanced overall metabolic health.

Notably, the study identified upregulation of oxidative phosphorylation and thermogenesis pathways, which increase energy metabolism in aSAT, providing a clearer picture of how regular exercise enhances metabolic function in people with obesity.

Background

In individuals with obesity, dysfunctional aSAT can contribute to insulin resistance and other metabolic problems. Issues such as reduced capillaries and increased inflammation in aSAT are linked to poor fat storage and the circulation of excess fatty acids, which can worsen metabolic health. By improving aSAT, particularly through enhanced fat storage and reduced inflammation, exercise could offer protective benefits.

This study aimed to fill the gap in understanding how long-term exercise affects aSAT, independent of weight loss, to explore how physical activity can improve cardiometabolic outcomes.

Study Overview

The researchers recruited 52 adults living with overweight or obesity. Participants were divided into exercisers and sedentary individuals based on their activity levels. The exercisers had consistently engaged in moderate to vigorous aerobic activity for over two years.

Key measures included body composition, fitness levels, and metabolic health markers. Fresh aSAT samples were collected to analyse structural and molecular differences between the groups.

Key Findings

Exercisers demonstrated significantly higher aerobic fitness and reported tenfold greater physical activity. They also had lower insulin resistance and higher HDL cholesterol levels compared to the sedentary group.

In terms of aSAT characteristics, exercisers had higher capillary density and increased levels of mitochondrial and ribosomal proteins, indicating better fat metabolism and energy production. Inflammatory markers were reduced, and proteins linked to metabolic dysfunction were lower in exercisers, suggesting improved tissue health.

Proteomic analysis identified 158 differentially expressed proteins, showing enhanced metabolic pathways in exercisers. These included the activation of the AMPK signalling pathway, essential for mitochondrial biogenesis and fat metabolism.

Conclusion

The study demonstrates that long-term endurance exercise leads to beneficial changes in fat tissue, boosting energy metabolism and improving cardiometabolic health in individuals with obesity. While short-term exercise offers some benefits, sustained physical activity is crucial for significant improvements in fat tissue function and overall health.

Yoyo dieting disrupts gut health and drives weight regain and inflammation

A review from Deakin University, Australia, published in Nutrients, reveals the profound effects of yoyo dieting (cycles of weight loss and regain) on gut health. The review highlights how weight cycling leads to gut inflammation, changes in microbiota, and adaptations in the sympathetic nervous system (SNS), which together drive weight regain.

Background

Obesity now affects over half of the global adult population and is linked to millions of deaths from diseases such as cardiovascular disease and type 2 diabetes. One of the major challenges in managing obesity is sustaining weight loss. Studies show that most people regain lost weight within five years, a phenomenon known as yoyo dieting or weight cycling.

This weight cycling not only increases the risk of obesity-related conditions but also disrupts gut health. The review points to emerging evidence that weight regain alters gut microbiota, with adaptive metabolic responses further complicating long-term weight management.

Gut Hormones and Energy Balance

Energy balance—the balance between intake and expenditure—is regulated by signals from the gut, pancreas, and adipose tissue. Many of these signals come in the form of peptide hormones that either promote satiety or stimulate hunger. After weight loss, individuals often experience lower levels of satiety hormones (PYY, GLP-1, and CCK) and higher levels of hunger hormones like ghrelin. This hormonal imbalance makes maintaining weight loss difficult, driving overeating and weight regain.

The review also discusses how weight loss can reduce enteroendocrine cells (EECs), which produce these key hormones, further impairing the body’s ability to regulate hunger and satiety.

The Role of the Gut Microbiota

The gut microbiota, which plays a critical role in energy regulation, also undergoes changes during and after weight loss. Beneficial bacteria that produce short-chain fatty acids (SCFAs), such as Christensenella and Lactobacillus reuteri, often decline during yoyo dieting, impairing satiety and promoting weight regain. Conversely, weight regain is associated with an increase in pro-inflammatory bacteria, such as Desulfovibrio and Ruminococcus, which contribute to metabolic disorders and gut inflammation.

Yoyo Dieting and Inflammation

Yoyo dieting exacerbates obesity-related chronic inflammation. Studies show that weight regain triggers inflammatory responses in the gut, marked by elevated levels of inflammatory markers such as TNF-α and IL-6. This inflammation can compromise gut barrier function, worsening metabolic health.

Improving Gut Health After Weight Loss

While yoyo dieting is associated with negative changes in the gut, weight loss has been shown to improve gut health by reducing inflammation and promoting the growth of beneficial bacteria like Akkermansia and Bifidobacterium. However, research indicates that the gut microbiota may take considerable time to return to a healthier state, leaving individuals vulnerable to weight regain during this period.

Research Gaps and Conclusions

Though animal studies have highlighted important links between yoyo dieting and gut health, more human studies are needed to fully understand how weight cycling affects the gut microbiota and weight regain. The review concludes that while weight loss can improve gut health, the molecular mechanisms behind these changes are still unclear, and more research is needed to develop effective strategies for preventing weight regain.

In conclusion, yoyo dieting disrupts gut health, leading to hormonal imbalances, inflammation, and microbiota changes that drive weight regain. Addressing these factors could be key to improving long-term weight maintenance and reducing obesity-related health risks.

Cellularsludge in hunger-regulating neurons linked to worsening diabetes and obesity

A recent study published in Nature has identified a mechanism through which inflammation in the hypothalamus promotes fibrotic changes in the perineuronal nets (PNNs), a specialised extracellular matrix (ECM) in the arcuate nucleus (ARC). These changes contribute to metabolic dysfunction, worsening conditions like obesity and diabetes.

Background

When blood glucose levels rise, insulin is released from pancreatic beta cells and signals the ARC to regulate hunger and metabolism. However, loss of insulin sensitivity leads to overeating and fat accumulation, contributing to obesity. The ECM, a network of proteins and sugars surrounding cells, plays a crucial role in this process. In people with obesity, the ECM undergoes fibrotic changes, particularly around Agouti-Related Protein (AgRP)-releasing neurons in the hypothalamus, disrupting insulin signalling and contributing to metabolic diseases.

Study Overview

In the study, researchers fed mice a regular or a high-fat, high-sugar (HFHS) diet to induce diabetes. They investigated whether neuroinflammation contributed to fibrotic buildup in the ECM by performing immunohistochemistry and stereotaxic injections. The team selectively disrupted insulin receptors in AgRP neurons to determine if ECM fibrosis impaired insulin function. They also used insulin tagged with fluorescein isothiocyanate (FITC) to track its signalling in hypothalamic neurons.

To assess the effects of inflammation, the team used adeno-associated viruses (AAVs) expressing receptors for pro-inflammatory TNF-α and anti-inflammatory TGF-β, alongside chondroitinase ABC (chABC), which breaks down fibrotic nets. Patch-clamp electrophysiology tested insulin interaction with PNNs in vitro, and fluorosamine, a drug inhibiting chondroitin sulphate synthesis, was administered to evaluate its therapeutic potential.

Key Findings

The study revealed that obese mice exhibited increased fibrotic PNNs around ARC neurons, disrupting insulin signalling and increasing AgRP neuron firing. Enzymatic breakdown of these PNNs restored insulin sensitivity, improved glucose metabolism, and reduced weight. The fibrosis altered gene expression for insulin receptors, exacerbating insulin resistance. While fibrotic nets impaired insulin activity, they did not affect leptin, the body weight-regulating hormone.

Additionally, obesity heightened levels of the inflammatory marker TNF-α while reducing the anti-inflammatory TGF-β, leading to increased fibrotic buildup. Reducing hypothalamic inflammation improved ECM function, and fluorosamine restored insulin sensitivity and improved metabolic outcomes in obese mice.

Conclusion

This study shows that hypothalamic ECM remodelling plays a significant role in metabolic diseases. Drugs targeting fibrotic PNNs and inflammation in the hypothalamus could improve insulin sensitivity and offer new treatments for obesity and diabetes by enhancing metabolic function.

Ultra-processed foods linked to increasing type 2 diabetes risk

Extensive research has demonstrated that the consumption of ultra-processed foods (UPFs) has a detrimental impact on the development of type 2 diabetes mellitus (T2D). However, the exact influence of other levels of food processing on T2D risk remains uncertain. A recent study published in The Lancet Regional Health sheds new light on this issue, exploring the association between varying degrees of food processing and the risk of developing T2D.

Food Processing and Its Relationship with Type 2 Diabetes

The Nova classification system is widely used to categorise foods based on the extent of their processing. According to this system, foods are divided into four categories: unprocessed or minimally processed foods (MPFs), processed culinary ingredients (PCIs), processed foods (PFs), and ultra-processed foods (UPFs). Research has long associated higher consumption of UPFs with weight gain, obesity, T2D, and cardiovascular diseases. A study conducted as part of the European Prospective Investigation into Cancer and Nutrition (EPIC) initiative revealed that a higher intake of UPFs is also linked to an increased risk of cancer and cardiometabolic multimorbidity.

Despite these findings, the link between T2D and all categories of processed foods, including MPFs, PCIs, and PFs, has yet to be fully elucidated. Further research is necessary to determine whether UPFs or other processed foods are most closely associated with adverse health outcomes. Gaining a deeper understanding of the impact of different types of processed foods may provide researchers with crucial insights into the benefits of replacing UPFs with healthier alternatives, such as MPFs, PCIs, or PFs.

The Study Overview

The recent cohort study used data from the EPIC project to explore the relationship between various food processing categories and T2D risk. Researchers assessed participants’ dietary intake at the start of the study by administering comprehensive dietary questionnaires. Based on this information, food consumption patterns were categorised according to the Nova classification system.

In order to identify cases of T2D, researchers relied on multiple data sources, including participants’ self-reports, primary and secondary care registers, hospital admission records, medication registers, and mortality data. The analysis used Cox regression and statistical substitution models to estimate the associations between T2D risk and the intake of MPFs, PCIs, PFs, and UPFs. Sub-group analyses were also conducted to identify any potential variations in the association between different UPFs and T2D risk.

The average age of the study participants was 52.5 years, and 63.5% of them were female. The average body mass index (BMI) was 25.7 kg/m², indicating that most participants were classified as being slightly overweight. Over the course of a 10.9-year follow-up period, 4.6% of participants were diagnosed with T2D. On average, MPFs and PCIs contributed to 72.1% of participants’ daily dietary intake, while UPFs accounted for 13.0%, and PFs made up 14.9%.

Key Findings of the Study

In examining the relationship between food processing and the development of T2D, the researchers conducted restricted cubic spline analyses to assess the intake of MPFs and PCIs. These analyses revealed a linear relationship between higher consumption of MPFs + PCIs and a lower risk of T2D up until very high intakes. Additionally, the study found that increased consumption of MPFs + PCIs, as well as PFs, was linked to a reduced risk of T2D. In contrast, a higher intake of UPFs was associated with an elevated risk of developing T2D.

To better understand the impact of replacing certain food groups on T2D risk, the researchers performed statistical substitution analyses. These analyses revealed that substituting 10% of UPFs with either MPFs + PCIs or PFs significantly reduced the risk of T2D. Moreover, replacing MPFs + PCIs with PFs also resulted in a reduction in T2D risk. These results held even after accounting for confounding factors such as saturated fat intake, sugar consumption, and adherence to a Mediterranean diet.

When investigating different sub-groups of UPFs, the study uncovered significant heterogeneity in their relationship with T2D. For instance, an increase in the consumption of savoury snacks, ready-to-eat or heat dishes, animal-based products, and artificially or sugar-sweetened beverages (ASBs/SSBs) was associated with a higher risk of T2D. On the other hand, lower T2D risk was linked to the consumption of plant-based alternatives, sweets and desserts, biscuits, breakfast cereals, and breads. Interestingly, no significant association was found between T2D and the consumption of sauces, spreads, condiments, alcoholic beverages, or other miscellaneous UPFs.

The Role of Adiposity in the UPF-T2D Relationship

To further understand the mechanisms underlying the association between UPF consumption and T2D, the researchers conducted mediation analyses focused on the waist-height ratio (WHtR), a measure of adiposity. These analyses revealed that WHtR mediated 46.4% of the association between UPF consumption and T2D risk. This suggests that body fat distribution may play a significant role in the relationship between UPF intake and the development of T2D.

Despite the robustness of the findings, some inconsistencies were noted in sensitivity analyses. For example, in France and Italy, the study did not find a statistically significant association between UPF consumption and T2D risk. Additionally, when the intake of MPFs + PCIs was modelled as kcal/day, %kcal/day, or g/day, no significant association with T2D risk was observed.

Conclusions

This study reinforces the growing body of evidence linking higher consumption of ultra-processed foods with an increased risk of type 2 diabetes mellitus. At the same time, it highlights the protective effect of consuming less processed foods, such as minimally processed or processed culinary ingredients, against the development of T2D.

Importantly, the findings point to the significant heterogeneity within the category of UPFs, suggesting that not all UPFs pose the same level of risk. This variability underscores the need for more nuanced public health guidelines, which should focus on reducing the intake of specific harmful UPFs rather than treating UPFs as a single, homogenous group. By encouraging people to make healthier food choices and reduce their consumption of certain types of UPFs, it may be possible to mitigate the rising global incidence of type 2 diabetes.

Childhood obesity associated with elevated risk of schizophrenia in adulthood, study finds

A team of medical researchers and disease management specialists in China has identified a significant link between obesity during childhood and the development of schizophrenia in adulthood. The study, published in the journal Science Advances, involved a comprehensive analysis of health records from two major genetic research projects. The findings underscore the potential long-term mental health consequences of childhood obesity, which was previously linked primarily to physical health issues.

Exploring the Link Between Childhood Obesity and Mental Health

Previous studies have established that obesity in childhood can contribute to various health complications both during childhood and in later life, including conditions like diabetes, cardiovascular disease, and metabolic syndrome. However, the research team sought to explore whether childhood obesity might also increase the risk of developing mental health disorders.

To investigate this, the researchers analysed data from the Psychiatric Genomics Consortium, an extensive project aimed at uncovering the genetic foundations of psychiatric illnesses. Additionally, they examined data from the FinnGen partnership, another major initiative focusing on genetic diseases. By utilising these large-scale genetic databases, the researchers aimed to uncover any associations between childhood obesity and the occurrence of mental health disorders in adulthood.

Examining Mental Health Outcomes in Later Life

The team specifically looked at the health outcomes of individuals who were classified as obese during their childhood and tracked the development of mental health issues as they aged. The mental health conditions they focused on included obsessive-compulsive disorder (OCD), major depression, anxiety disorders, Alzheimer’s disease, and schizophrenia. Interestingly, the researchers found no significant associations between childhood obesity and any of these mental health conditions except for schizophrenia.

The study’s authors describe the evidence linking childhood obesity to an increased risk of schizophrenia in adulthood as “compelling and direct.” Crucially, they found that this link was independent of obesity later in life and other lifestyle factors. This suggests that the risk of developing schizophrenia is specifically associated with excess weight during the childhood years rather than ongoing obesity in adulthood.

The Unexplained Mechanism Behind the Link

Despite establishing a correlation between childhood obesity and schizophrenia, the researchers were unable to determine the exact mechanism behind this relationship. They speculated that the accumulation of excess fat during childhood might influence brain development in ways that predispose individuals to schizophrenia later in life. However, further research is needed to understand how obesity-related changes in the brain during critical developmental periods could lead to this increased risk.

A Surprising Finding: Adult-Onset Obesity and Schizophrenia Risk

In a separate analysis, the team discovered an unexpected outcome: individuals who were not obese as children but became obese during adulthood were actually less likely to develop schizophrenia or OCD. This finding adds complexity to the understanding of how obesity and mental health are connected, suggesting that the timing of obesity onset could play a crucial role in its potential impact on psychiatric health. It also indicates that adult-onset obesity may not carry the same mental health risks as childhood obesity, at least in relation to schizophrenia and OCD.

Implications for Public Health and Policy

The researchers emphasise the importance of childhood obesity prevention as a means of potentially reducing the risk of developing schizophrenia in later life. They argue that these findings highlight the need for health care policies and programmes aimed at preventing children from becoming overweight. Early intervention strategies, education on nutrition, and promoting physical activity in children could be key in addressing this public health issue.

As they conclude, the study presents a strong case for the importance of childhood health and its potential lifelong implications. It suggests that the consequences of obesity are not limited to physical health but may extend to mental health in ways that are only beginning to be understood. Further research into the mechanisms connecting childhood obesity and schizophrenia is required to develop more targeted prevention and treatment strategies.

NHS limiting access to essential obesity services across England, British Medical Journal reveals

The National Health Service (NHS) is restricting access to crucial obesity services across England, leaving individuals in nearly half of the country without the ability to seek appointments with specialist teams for necessary support and treatments, including weight-loss injections. 

This concerning situation was uncovered through an investigation by the British Medical Journal (BMJ), which mirrors the findings of a recent report by the Future Health research agency. The agency’s report highlighted that many of England’s Integrated Care Boards (ICBs) have failed to establish detailed strategies to address obesity and provide treatment, despite the condition costing the United Kingdom an estimated £98 billion annually in healthcare expenses, lost productivity, and other associated costs.

Richard Sloggett, the report’s author and a former special adviser in the Department of Health and Social Care, described these new revelations as evidence of the NHS “rationing” obesity treatment. He emphasised, “These findings back up our Future Health research showing that many ICBs do not currently see obesity as a priority. In certain parts of the country, there is no access to tier 3 and tier 4 services at all. This rationing is leading to a postcode lottery of care. Given the scale of the obesity challenge facing the country and the wider health and economic costs and impacts associated with it, there is an urgent need for the government and the NHS to commit new action. This should start with a clear timeline for reviewing NHS obesity services and ensuring there is a minimum service specification agreed and in place in each ICB.”

A spokesperson for NHS England responded to the BMJ’s investigation by stating that the NHS was “working with the Department of Health to support improvements in the obesity pathway.” However, experts argue that more decisive action is needed.

The BMJ’s investigation also revealed that budget cuts have disproportionately impacted local services focused on obesity care. Individuals living with obesity are often viewed as less deserving of care compared to those with other health conditions, exacerbating the situation. This reality has led to what one expert describes as a “postcode lottery of care,” where access to obesity services varies significantly depending on geographical location.

Data collected through freedom of information requests sent to all 42 of England’s ICBs showed that patients in one in six local healthcare areas were unable to access bariatric surgery, a treatment considered one of the most clinically effective interventions for obesity.

Dr Nicola Heslehurst, a professor of maternal and child nutrition at Newcastle University and chair of the UK Association for the Study of Obesity, voiced her concerns about the current state of weight management services. She told the BMJ, “Current weight management services do not in any way meet the need,” and warned that “radical” action was necessary to combat the rising prevalence of obesity, the associated care costs, and health inequalities. She also stressed the impact on future generations, cautioning that without intervention, children may be “set up for a life course of poor health.”

Obesity imposes a significant financial burden on the NHS in England, costing an estimated £6.5 billion each year. It is also recognised as the second leading cause of cancer after smoking, highlighting the urgency for a comprehensive and effective response.

ICBs receive funding from NHS England to deliver healthcare services for their local communities. However, recent budget cuts have placed immense financial pressure on these boards. In many cases, when resources are limited, services perceived as lower priority are denied funding, with obesity care frequently being the first to face budget reductions.

The BMJ’s investigation found that just over half (24) of England’s 42 ICBs commissioned the full spectrum of adult weight loss services and were open to new referrals. These services range from localised diet and lifestyle classes to more advanced interventions, such as semaglutide weight-loss injections (marketed as Wegovy) and gastric bypass surgery.

However, over a third of ICBs reported imposing restrictions on tier three obesity services, which involve multidisciplinary teams capable of prescribing weight-loss medications. Among these ICBs, six had closed their services to new patients, seven provided services only to certain parts of their catchment area, and four lacked any tier three services altogether.

Tier four services, which include more intensive weight-management interventions like gastric bypass surgery, are also severely restricted. The investigation found that seven ICBs do not offer any bariatric surgery, further highlighting the disparities in access to care across different regions of England.

John Wilding, a professor of medicine at the University of Liverpool, criticised the lack of prioritisation for obesity services, stating, “Obesity services are not deemed a priority.” He also pointed out a prevailing bias within the healthcare system, noting, “I think there is an unconscious bias which says: ‘This is mostly their fault, so they should just get on with it, go on a diet and lose weight.’ But we know from genetics and other factors that it’s much more complicated than that.”

These findings underscore an urgent need for a comprehensive review of NHS obesity services and the establishment of a uniform standard of care across all ICBs. The current restrictions on access to essential obesity treatment services not only create health inequalities but also contribute to escalating healthcare costs and long-term negative health outcomes. Without significant changes in policy and practice, the NHS faces an ongoing struggle to address the obesity crisis effectively.