Scientists Identify a Possible Biological Link Between Obesity and Alzheimer’s
Key Takeaways:
- Researchers at Houston Methodist have identified phosphatidylethanolamines (PEs) – a class of fat molecule found in cell membranes – as a possible biological link between obesity and Alzheimer’s disease.
- Obesity appears to increase levels of these molecules in body tissue, after which they are packaged into tiny particles that travel to the brain, disrupting communication between brain cells, weakening immune protection and encouraging amyloid proteins to accumulate.
- Restoring a healthier balance of PEs reduced disruption in lipid regulation and improved brain function and cognitive performance in models of Alzheimer’s disease, pointing to a possible target for future treatments.
Why researchers are looking beyond the brain
Alzheimer’s disease has long been studied as a condition of the brain itself, defined by the amyloid plaques and tangles found in brain tissue. A growing body of research, however, suggests that the disease may be influenced by biological changes taking place far beyond the skull. Metabolic health – and obesity in particular – is now emerging as a possible contributor to the processes that worsen the disease.
New findings from Houston Methodist add weight to that idea. The study examined how changes in body fat associated with obesity may send damaging signals to the brain, where they appear to interfere with the brain’s immune system and contribute to the biological damage linked to Alzheimer’s disease.
The team behind the study
The research was co-led by Stephen Wong, Ph.D., the John S. Dunn Presidential Distinguished Chair in Biomedical Engineering, and Li Yang, Ph.D., a research associate in the Chao Center for BRAIN at Houston Methodist. The findings were published in the journal Molecular Neurodegeneration.
Fat molecules may connect obesity and Alzheimer’s disease
At the centre of the work is a class of lipid, or fat molecule, called phosphatidylethanolamines, abbreviated to PEs. These molecules are found in cell membranes throughout the body, where they form part of the basic structure of every cell.
According to the study, obesity raises the amount of these molecules in body tissue. The PEs are then loaded into tiny particles that are capable of travelling through the body and reaching the brain – effectively carrying a metabolic signal from fat tissue to the central nervous system.
What happens once these particles reach the brain
Once inside the brain, these particles appear to do three things at once. They can interfere with communication between brain cells, they can weaken immune protection, and they can encourage amyloid proteins to accumulate. Amyloid buildup is one of the major biological features associated with Alzheimer’s disease.
That combination matters, because it suggests obesity is not simply sitting alongside Alzheimer’s risk as a separate problem, but may be actively feeding into the mechanisms that drive the disease.
“Obesity can change how signals travel to the brain,” Wong said. “The good news is that this may be something we can treat. Instead of looking at Alzheimer’s risk tied to obesity as just a metabolic problem, this research suggests we may be able to target the process that connects those changes to the brain.”
Restoring lipid balance improved brain function
The findings also suggest a possible direction for future treatments. When the researchers restored a healthier balance of PEs, they observed less disruption in lipid regulation.
Correcting the imbalance also improved brain function and cognitive performance in models of Alzheimer’s disease. Cognitive performance refers to abilities such as learning, memory, attention and problem solving – the domains most visibly affected as Alzheimer’s progresses.
Taken together, these results suggest that targeting the fat molecules themselves, or the pathway that carries them to the brain, could potentially reduce some of the damage associated with obesity and Alzheimer’s disease.
A growing public health challenge
The stakes are considerable. According to the Centers for Disease Control and Prevention, more than 6.5 million Americans are living with Alzheimer’s disease. That total is expected to rise to nearly 14 million by 2060.
Yang emphasised that a good deal more research will be required before treatments aimed at PEs can be tested as prevention or therapy in people. Even so, the findings introduce a possible strategy for intervening earlier in individuals whose metabolic health may place them at greater risk of Alzheimer’s disease.
What this may mean for practice
For healthcare professionals, work of this kind reinforces a message that has been building across obesity research for some years: excess weight is bound up with a wide range of downstream conditions through complex biological pathways, rather than existing in isolation. Understanding those pathways – and being able to discuss them sensitively with patients – is increasingly part of everyday clinical conversation. CCH’s Obesity Essentials CPD short course is designed with exactly that in mind, introducing the many factors that cause and contribute to obesity alongside the practical skills needed to assess and support people living with overweight and obesity.
It is worth being clear about the limits of the current evidence. The results described here come from laboratory models rather than clinical trials in people, and no PE-targeted treatment is close to being available. What the study offers is a plausible mechanism and a candidate target – both of which are needed before prevention strategies aimed at metabolic risk can be tested properly.
Study collaborators and funding
Other collaborators on the study include Li Yang, Jianting Sheng, Shaohua Qi, Zheng Yin, Michael Chan, Yuliang Cao, Hong Zhao, Zhihao Wan, Bill Chan, Ju Ahn, Xiaohui Yu, Matthew Vasquez and Shan Xu from Houston Methodist; Xianlin Han from the University of Texas, San Antonio; Weiming Xia from Boston University; and Willa Hsueh from Ohio State University.
The study was funded by grants from the Cure Alzheimer’s Fund, the T.T. and W.F. Chao Foundation, and the John S. Dunn Research Foundation.
CCH insight
Research linking obesity to conditions well beyond metabolic health is reshaping how clinicians talk to patients about weight. CCH’s Obesity Essentials online CPD short course gives healthcare professionals the knowledge and confidence to assess and manage overweight and obesity effectively, and to hold those conversations with compassion and clarity. The course takes 8–10 hours, is completed entirely online at your own pace, and carries 10 CPD hours plus a certificate of completion.
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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.
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Abdominal Obesity and Vitamin D Deficiency Together More Than Double the Risk of Death After 50
Key Takeaways:
- In people aged 50 and over, having both abdominal obesity and vitamin D deficiency was linked to a 123% higher risk of death.
- Alone, abdominal obesity raised that risk by 47% and vitamin D deficiency by up to 91% – together, the two amplify one another.
- Abdominal fat sequesters circulating vitamin D, and the resulting deficiency worsens the chronic inflammation driven by excess fat.
A six-year study of ageing in England
New research has put a figure on something clinicians have long suspected: that two common and often overlooked problems in later life are considerably more dangerous when they occur together than either is alone.
The study, in the journal Diabetes, Obesity and Metabolism, followed 5,520 people aged 50 and older over a six-year period. It found that people with both abdominal obesity and vitamin D deficiency had a 123% higher risk of death than people without these conditions.
The work was coordinated by Tiago Silva Alexandre, a professor in the Department of Gerontology at the Federal University of São Carlos (UFSCar) in Brazil, and carried out in collaboration with University College London (UCL) in the United Kingdom. Participants were drawn from the English Longitudinal Study of Ageing (ELSA), one of the world’s largest studies on ageing.
The central message is not that either condition is newly dangerous, but that their combination multiplies risk.
“Abdominal obesity is a well-known risk factor because it’s associated with inflammation and metabolic problems. Vitamin D, on the other hand, is a hormone that acts on various organs, and its deficiency impairs several bodily functions. When these two conditions occur together, one amplifies the effects of the other, further increasing the risk of death,” explains Alexandre. “For that reason, monitoring vitamin D levels and treating excess abdominal fat are essential measures to prevent premature death, especially after age 50,” he adds.
How the two conditions were defined
The researchers used established thresholds for both measures, which makes the findings straightforward to translate into everyday practice.
Vitamin D deficiency was defined as a level below 30 nmol/L. Abdominal obesity was defined by waist circumference – greater than 102 centimetres (40 inches) for men and greater than 88 centimetres (35 inches) for women.
Both are measures that can be captured in a routine consultation, one through a standard blood test and the other with a tape measure, without recourse to specialist equipment or imaging.
Each condition carries risk on its own
When the two conditions were examined separately, the data produced a result that may surprise some practitioners: vitamin D deficiency alone posed a greater risk than abdominal obesity alone.
Abdominal obesity on its own was associated with a 47% increase in the risk of death. Vitamin D deficiency on its own raised that risk by up to 91%. When both were present, the risk of death more than doubled.
That pattern is what makes the combination clinically significant. The elevated risk seen in people with both conditions is greater than would be expected from simply adding the two individual risks together, which points towards a biological interaction rather than two independent problems sitting side by side in the same person.
Why the two conditions amplify one another
According to Alexandre, abdominal obesity and vitamin D deficiency feed into each other, creating what he describes as a vicious cycle.
The first mechanism is storage. Abdominal fat “sequesters” circulating vitamin D and holds it within adipocytes, or fat cells, preventing the vitamin from reaching the bloodstream in useful quantities.
“This means that although the body may have the vitamin stored in fat, it isn’t freely available in the blood to perform vital functions in other organs and systems,” he says.
In other words, a blood test may show deficiency even where the body’s total stores are not depleted, because the vitamin is effectively locked away where it cannot be used.
The second mechanism concerns metabolism. People with obesity have lower expression of the enzymes needed to metabolise vitamin D, which further reduces the amount available to the body.
The consequences then loop back on themselves. “Abdominal obesity reduces circulating vitamin D, and that deficiency impairs the immune system, exacerbating the chronic inflammation caused by excess fat and drastically increasing the risk of mortality,” Alexandre explains to Agência FAPESP.
Ageing, inflammation and a loss of regulation
The picture is complicated further by the biology of ageing itself. Later life is naturally marked by a process known as inflammaging – a state of low-grade chronic inflammation that develops with age.
Vitamin D ordinarily acts as a brake on that process. Where levels fall and abdominal fat is present, that brake is weakened at precisely the point where it is most needed.
“Under normal conditions, vitamin D acts as a regulator of the immune system, preventing inflammation from getting out of control. When vitamin D levels are low and there’s excess abdominal fat, an unfavorable systemic environment develops that accelerates cardiovascular and metabolic diseases, as well as muscle loss,” he stresses.
Part of a wider cascade
This study is the most recent in a series by the same group investigating the role of vitamin D in ageing, and its findings sit alongside earlier work linking deficiency to functional decline.
“In previous studies, we identified a cascade effect. Vitamin D deficiency leads to a loss of strength, which results in reduced walking speed, causing a loss of independence and greater dependence in daily activities,” Alexandre explains.
A further study by the group found that vitamin D deficiency increases the risk of cognitive decline.
Taken together, these strands describe a hormone with a reach that extends well beyond bone health.
“Vitamin D is a hormone with various functions. It plays a role in regulating blood pressure, heart rate, the central nervous system, the immune system and the endocrine system. Therefore, when its levels are low, several essential bodily functions are compromised,” he says.
What this means for practice
For healthcare professionals working with people over 50, the practical implication is a case for looking at these two markers together rather than in isolation. A raised waist circumference and a low vitamin D level each warrant attention on their own terms, but the study suggests that the presence of one should prompt closer interest in the other.
It also reinforces the value of waist circumference as an assessment measure in its own right, given that it is central adiposity – rather than body weight alone – that drives the inflammatory and metabolic processes described here.
Building that broader assessment skill set, and the confidence to act on it as part of whole-person care, is the focus of professional training such as the College of Contemporary Health’s Obesity Essentials, a CPD-accredited online short course covering the assessment and management of overweight and obesity.
As Alexandre puts it, monitoring vitamin D levels and treating excess abdominal fat are essential measures to prevent premature death after the age of 50 – two simple assessments that, on this evidence, carry considerable weight together.
CCH insight
This is an interesting study. At CCH we have held a longstanding interest in the wide- ranging functions of vitamin D, especially its role in immune function. These results suggest that vitamin D status should be checked routinely in patients with abdominal obesity, and any deficiency should be treated immediately. This would be a simple and inexpensive protocol and could significantly reduce premature death in this group.
Findings like these are a reminder that excess abdominal fat rarely acts alone – its metabolic and inflammatory effects reach into hormone regulation, immune function and, ultimately, life expectancy. CCH’s Obesity Essentials CPD short course (10 CPD hours, fully online, CPD-accredited) helps healthcare professionals assess and manage patients living with overweight and obesity using a rounded, evidence-based approach that looks beyond a single number on the scale to the wider systemic picture.
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New Research Shows Obesity May Reshape How Breast Cancer Spreads
Key Takeaways:
- Obesity may alter how early, non-invasive breast lesions progress into invasive cancer, a University of Oklahoma study suggests.
- In women with obesity, progression was linked to inflammation, immune cell activity, metabolic changes and raised levels of the enzyme SULF2 – not the rapid cell division seen in women without obesity.
- The findings could improve risk prediction for women with DCIS and help reduce overtreatment.
A different route to invasive disease
Obesity may change how early-stage breast cancer becomes invasive, according to a study by University of Oklahoma researchers published in The American Journal of Pathology.
Obesity is already recognised as a risk factor for invasive breast cancer, but researchers have not fully understood how it helps early, non-invasive breast lesions develop into invasive cancer. A clearer picture of this process could strengthen physicians’ ability to predict and treat the disease.
In the study, breast cancers in women without obesity displayed the typical signs of turning invasive, including rapid cell division and an increased ability to invade neighbouring tissue. In women with obesity, however, the researchers identified a different set of biological changes that appeared to help the cancer become invasive.
The cancer environment became more inflamed, with the arrival of immune cells that advanced the growth of the tumour. The tumour cells also appeared better able to survive under stress, and there were changes in cellular metabolism – how the cells use nutrients for energy.
“This could be why women with obesity are at higher risk for invasive breast cancer,” said Bethany Hannafon, Ph.D., co-lead author of the study and an assistant professor in the Department of Obstetrics and Gynecology at the OU College of Medicine. “The changes that the cancer cells are undergoing are allowing them to survive and thrive.”
A cooperative cancer “neighbourhood”
The researchers also found differences in the “neighbourhood” of cells and tissues surrounding the cancer. Epithelial cells, where the tumour originally develops, co-opt other cells around them to create an environment that is even more conducive to cancer growth.
“In women with obesity, there is cooperation between all the cell types, not just the cancer cells, which helps an early pre-cancer to become an invasive breast cancer,” said co-lead author Elizabeth Wellberg, Ph.D., assistant professor in the Department of Pathology at the OU College of Medicine. “That may be an area of future study – can a drug or intervention that targets only one cell type interrupt the whole network of progression toward invasive cancer?”
The role of the enzyme SULF2
The research team additionally discovered higher levels of an enzyme called Sulfatase 2 (SULF2) in the tumour cells of women with obesity, suggesting that it may play an important part in cancer progression. SULF2 will be a further focus of future studies.
Why better DCIS risk prediction matters
Understanding what causes early, non-invasive tumours – known as ductal carcinoma in situ, or DCIS – to become invasive is important because not all women will go on to develop invasive cancer, yet they currently receive the same treatment.
“In women diagnosed with DCIS, about half will later develop invasive ductal carcinoma (IDC) that spreads into surrounding breast tissue. But we currently have no way of determining which women are most at risk. As a result, many women with DCIS receive the same treatments used for IDC, including surgery, radiation and sometimes hormone therapy. Overtreatment is a major concern, but if we had better ways of determining risk, unnecessary treatments could potentially be reduced,” Hannafon said.
While breast cancer survival rates have improved over the past two decades, the number of women diagnosed with invasive breast cancer has not declined – underscoring the need for better ways to predict and prevent disease progression.
A growing public health concern
The rising prevalence of obesity gives the findings added weight.
“Obesity is on the rise – 50% of Americans are expected to be obese by 2030,” said the paper’s first author, Cole Hladik, Ph.D., who worked in Hannafon’s lab while earning his doctorate. “That statistic further highlights the importance of considering a patient’s metabolic health alongside the biology of the tumor itself.”
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Carbohydrate-Rich Diets May Promote Weight Gain Even Without Higher Calorie Intake
Key Takeaways:
- A new mouse study found that carbohydrate-rich foods such as bread, wheat flour, and rice flour promoted weight gain and fat accumulation even when total calorie intake did not significantly increase.
- Researchers observed that the weight gain appeared to be linked more closely to reduced energy expenditure and metabolic changes than to overeating.
- Scientists say future human studies will explore how factors such as whole grains, fibre content, food processing, meal timing, and combinations with protein and fat influence metabolic responses to carbohydrates.
Bread and carbohydrates under renewed scrutiny
Bread has served as a central part of human diets for centuries and remains a staple food in many cultures around the world. Foods such as bread, rice, noodles, and other carbohydrate-rich staples continue to form the foundation of everyday meals for billions of people.
However, as rates of overweight and obesity continue to increase globally, researchers are re-examining how modern dietary patterns may influence body weight and metabolic health. While high-fat diets have traditionally received much of the attention in obesity research, scientists are now taking a closer look at the role carbohydrates may play in weight regulation.
A new study led by researchers at Osaka Metropolitan University suggests that certain carbohydrate-heavy eating patterns may contribute to weight gain in ways that are not solely explained by consuming more calories.
The findings were published in Molecular Nutrition & Food Research.
Obesity research has traditionally focused on fat intake
Obesity is associated with a broad range of chronic conditions and lifestyle-related diseases, including type 2 diabetes, cardiovascular disease, and metabolic dysfunction. Because of this, understanding the drivers of weight gain has become an increasingly important area of scientific research.
Historically, many obesity studies have focused primarily on dietary fat as the main contributor to excess weight gain. This is reflected in the widespread use of high-fat diets in animal research investigating obesity and metabolism.
At the same time, carbohydrate-rich foods remain deeply embedded in daily diets across the world. Despite their prominence, the metabolic effects of staple carbohydrates such as bread, rice, and noodles have not always been explored in the same depth.
Public perceptions around carbohydrates also remain widespread. Beliefs such as “bread makes you gain weight” or “carbohydrates should be restricted” are common, yet researchers say it has remained unclear whether such effects are driven by the foods themselves, overall dietary habits, eating behaviour, or broader metabolic responses.
Researchers investigated how carbohydrate-rich foods affect metabolism
To better understand the relationship between carbohydrates and weight gain, researchers led by Professor Shigenobu Matsumura at Osaka Metropolitan University’s Graduate School of Human Life and Ecology conducted a series of experiments in mice.
The study examined whether mice would preferentially select carbohydrate-rich foods over standard laboratory chow and how those dietary choices would affect body weight, metabolism, and energy expenditure.
The mice were separated into several dietary groups, including:
- Chow
- Chow + Bread
- Chow + Wheat Flour
- Chow + Rice Flour
- High-fat diet (HFD) + Chow
- High-fat diet (HFD) + Wheat Flour
Researchers monitored multiple metabolic indicators throughout the study, including:
- Body weight
- Fat mass
- Energy expenditure
- Blood metabolites
- Liver gene activity
Mice preferred carbohydrate-rich foods
The researchers found that mice consistently showed a strong preference for carbohydrate-rich foods. Animals given access to bread, wheat flour, or rice flour largely abandoned their standard chow diet in favour of these carbohydrate sources.
Importantly, the researchers reported that overall calorie intake did not increase substantially despite this dietary shift. Nevertheless, mice consuming the carbohydrate-rich diets still experienced increases in body weight and fat mass.
Rice flour produced similar effects to wheat flour, suggesting the observed metabolic changes were not specific to wheat itself.
Interestingly, mice in the High-fat diet (HFD) + Wheat flour group gained less weight than those in the High-fat diet (HFD) + Chow group, indicating that the interaction between fat and carbohydrate intake may be more complex than previously assumed.
“These findings suggest that weight gain may not be due to wheat-specific effects, but rather to a strong preference for carbohydrates and the associated metabolic changes,” said Professor Matsumura.
Reduced energy expenditure appeared to play a key role
To investigate why the mice gained weight without substantially increasing calorie intake, the researchers carried out further metabolic analysis using indirect calorimetry and respiratory gas measurements.
The findings suggested that the weight gain was not primarily caused by overeating. Instead, the animals appeared to experience reduced energy expenditure, meaning they were burning fewer calories.
Researchers also identified several metabolic changes in the mice consuming the carbohydrate-rich diets.
Blood analysis showed:
- Increased fatty acid levels
- Reduced levels of essential amino acids
Meanwhile, examination of the liver revealed:
- Greater fat accumulation
- Increased activity of genes involved in fatty acid synthesis
- Increased activity of genes associated with lipid transport
Together, these findings suggest that carbohydrate-heavy dietary patterns may alter how the body processes and stores energy.
Metabolic changes improved when carbohydrates were reduced
The researchers also observed that removing wheat flour from the diet rapidly improved both body weight and several metabolic abnormalities.
According to the authors, this finding suggests that moving away from a highly carbohydrate-focused dietary pattern and towards a more balanced eating pattern may help improve metabolic regulation.
However, the researchers emphasised that additional work is needed to determine how these findings translate to human diets and real-world eating behaviour.
Future studies will explore human dietary patterns
The research team says the next phase of investigation will focus on understanding whether similar metabolic effects occur in people.
“Going forward, we plan to shift our research focus to humans to verify the extent to which the metabolic changes identified in this study apply to actual dietary habits,” stated Professor Matsumura.
“We also intend to investigate how factors such as whole grains, unrefined grains, and foods rich in dietary fiber, as well as their combinations with proteins and fats, food processing methods, and timing of consumption, affect metabolic responses to carbohydrate intake. In the future, we hope this will serve as a scientific foundation for achieving a balance between ‘taste’ and ‘health’ in the fields of nutritional guidance, food education, and food development.”
The researchers noted that future studies examining food quality, fibre content, food combinations, and meal timing may help provide a more nuanced understanding of how carbohydrates influence metabolism and body weight.
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Parental Weight Before Pregnancy Linked to Higher Risk of Fatty Liver Disease in Adult Offspring, UK Study Finds
Key Takeaways:
- Pre-pregnancy overweight or obesity in either parent is associated with a significantly increased risk of metabolic dysfunction associated steatotic liver disease (MASLD) in their children by early adulthood.
- When both parents were living with overweight or obesity prior to conception, the likelihood of MASLD in offspring by age 24 was more than three times higher.
- Much of this increased risk appears to be mediated by excess weight accumulated during childhood and adolescence.
Rising concern over MASLD across generations
Parental weight status before pregnancy may play an important role in shaping long-term liver and metabolic health in the next generation, according to new research published online in Gut. The findings suggest that overweight and obesity in both mothers and fathers prior to conception are linked to a heightened risk of metabolic dysfunction associated steatotic liver disease (MASLD) in their children as young adults.
MASLD, previously known as non-alcoholic fatty liver disease, is now recognised as the most common chronic liver condition worldwide. Researchers note that the disease affects approximately 15% of children and more than 30% of adults globally. The condition is characterised by excess fat accumulation in the liver alongside cardiometabolic abnormalities and may progress to cirrhosis or liver failure in some individuals.
While earlier studies have primarily focused on maternal obesity, uncertainty has remained regarding the contribution of paternal weight and the role of childhood weight trajectories in determining future disease risk.
Large UK birth cohort provides long-term insight
To investigate these questions, researchers analysed data from 1,933 participants enrolled in the UK Avon Longitudinal Study of Parents and Children (ALSPAC), a long-running population study tracking health outcomes across generations.
The study examined associations between parental body mass index (BMI) before pregnancy and the likelihood that offspring would develop MASLD by the age of 24.
MASLD was defined as the presence of elevated liver fat together with at least one cardiometabolic risk factor, such as raised cholesterol levels or elevated fasting glucose.
Both parents provided information on height, weight, BMI and waist circumference before pregnancy. They also completed detailed questionnaires during pregnancy and following childbirth covering a wide range of potential influencing factors, including:
- Age at delivery
- Smoking during early pregnancy
- Weekly alcohol consumption prior to pregnancy
- Employment status
- Educational attainment
Mothers additionally reported physical activity levels and whether they had previously been diagnosed with diabetes or hypertension at study enrolment.
Tracking early life and adolescent risk factors
Extensive information was also collected about the children, allowing researchers to examine developmental influences across childhood and adolescence. Recorded factors included:
- Sex
- Mode of delivery
- Gestational age and birthweight
- Antibiotic exposure during the first six months of life
- Duration of breastfeeding
Participants underwent repeated measurements of BMI and waist circumference between the ages of 7–9, 10–12 and 13–17 years. Lifestyle factors in early adulthood, including alcohol and tobacco use, were also assessed.
One in ten young adults developed MASLD
By age 24, MASLD was identified in 201 participants, representing approximately one in ten individuals in the cohort. The remaining 1,732 participants had normal liver findings.
Those living with MASLD were more likely to be male and to have a higher BMI compared with peers without the condition.
After adjusting for multiple potential confounding factors, both maternal and paternal overweight or obesity before conception were independently associated with increased odds of MASLD in offspring.
Each additional kilogram per square metre of maternal BMI increased the likelihood of MASLD by 10%, while each equivalent increase in paternal BMI was associated with a 9% rise in risk.
Most notably, offspring whose parents were both living with overweight or obesity prior to pregnancy had more than three times the odds of developing MASLD compared with those whose parents had a normal BMI.
Childhood weight plays a central role
Further analysis suggested that much of this association operates through weight gain during childhood and adolescence. Researchers estimated that 67% of the increased risk linked to parental overweight or obesity was explained by cumulative excess BMI between the ages of 7 and 17.
Additional analyses incorporating maternal and offspring sugar intake, as well as genetic susceptibility to MASLD, produced similar results, strengthening confidence in the observed associations.
Observational findings with important limitations
The authors emphasise that the study was observational and therefore cannot establish direct causation. Several limitations were also acknowledged.
Parental weight data prior to pregnancy were self-reported, and information was unavailable regarding parental MASLD status or certain underlying health conditions before and during pregnancy. In addition, physical activity levels of offspring in early adulthood were not captured, which may have influenced outcomes.
Implications for preconception health
Despite these limitations, the researchers conclude that their findings highlight the potential importance of parental metabolic health before conception in shaping long-term outcomes for future generations.
They state that the results “lend support to an early life influence of biparental obesity on offspring metabolic health, suggesting efforts to mitigate excess adiposity of both mothers and fathers before conceiving may confer longitudinal benefits to the metabolic outcomes of their future offspring.“
The study adds to growing evidence that prevention of metabolic disease may need to begin not only in childhood, but even before pregnancy, with both parents playing a meaningful role in influencing lifelong health trajectories.
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