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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