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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Mice Study Connects Soybean Oil Intake to Liver Changes and Obesity
Key Takeaways:
- New research in mice suggests that weight gain linked to soybean oil is driven by the metabolic products of linoleic acid rather than the oil itself.
- Genetically engineered mice resistant to obesity on a high-fat soybean oil diet produced fewer oxylipins and showed healthier liver function.
- Scientists believe differences in human genetics, enzyme levels, and metabolic stress may influence people’s susceptibility to soybean-oil-related metabolic effects.
A closer look at soybean oil and obesity
Soybean oil is the most widely consumed cooking oil in the United States and is a key ingredient in many processed foods. A growing body of research has associated high intake of soybean oil with weight gain in animals. A new study from the University of California, Riverside (UCR), published in the Journal of Lipid Research, provides fresh insight into why this may occur.
Researchers found that mice consuming a high-fat diet rich in soybean oil gained considerable weight. However, a separate group of genetically engineered mice did not, despite eating the same diet. These altered mice carried a slightly different version of a liver protein that affects the expression of hundreds of genes involved in fat metabolism.
The findings point toward a metabolic mechanism that may help explain differences in weight gain among individuals exposed to similar diets.
“This may be the first step toward understanding why some people gain weight more easily than others on a diet high in soybean oil,” said Sonia Deol, a UCR biomedical scientist and corresponding author of the study.
The role of HNF4α in fat metabolism
In humans, both forms of the liver protein known as HNF4α occur naturally. However, the alternative version typically appears only under certain conditions, such as chronic illness, prolonged fasting, metabolic stress, or alcoholic fatty liver disease. These variations, combined with factors such as age, sex, medication use, and underlying genetics, may influence how different people respond to high levels of soybean oil in their diet.
The UCR team believes that the altered form of HNF4α in genetically engineered mice changes how the body processes linoleic acid, a major fatty acid in soybean oil.
Building on earlier research
The study adds to previous findings from the same research group.
“We’ve known since our 2015 study that soybean oil is more obesogenic than coconut oil,” said Frances Sladek, a UCR professor of cell biology. “But now we have the clearest evidence yet that it’s not the oil itself, or even linoleic acid. It’s what the fat turns into inside the body.”
One of the major metabolic products of linoleic acid is a group of molecules called oxylipins. These compounds are associated with inflammation, fat accumulation, and other metabolic changes.
Oxylipins and their link to weight gain
Mice engineered to produce the alternative form of HNF4α showed markedly lower levels of oxylipins in their livers, despite consuming a high-fat soybean oil diet. They also had healthier liver profiles and enhanced mitochondrial function. Improved mitochondrial activity may help explain their resistance to weight gain.
Researchers pinpointed specific oxylipins derived from both linoleic acid and alpha-linolenic acid (another fatty acid found in soybean oil) that appeared necessary for weight gain in regular mice.
However, the picture is complex. Even though transgenic mice on a low-fat diet showed elevated oxylipin levels, they did not become obese. This suggests that while these molecules contribute to weight gain, they are unlikely to be the sole drivers. Other metabolic conditions must also play a role.
Genetic variation in enzyme levels
Further analysis revealed that the modified mice had far lower levels of two key enzyme families responsible for converting linoleic acid into oxylipins. These enzymes are highly conserved across all mammals, including humans, and can vary significantly from person to person based on factors such as genetics and diet.
The scientists also observed that oxylipin levels in the liver, rather than in the bloodstream, were correlated with body weight. This indicates that standard blood tests may not reliably detect early metabolic disturbances linked to diet.
Soybean oil’s rise in the American diet
Soybean oil consumption in the United States has risen dramatically over the past century. It has increased from around 2 percent of total daily calories to almost 10 percent. Although soybeans provide protein and the oil contains no cholesterol, modern diets deliver far greater quantities of linoleic acid than the body is likely evolved to manage.
In line with this, the UCR study found that soybean oil intake was associated with increased cholesterol levels in mice despite the oil containing no dietary cholesterol. This reflects the complex interplay between dietary fats and internal metabolic pathways.
Questions for future research
The team now aims to understand precisely how oxylipin formation leads to weight gain and whether oils with similarly high linoleic acid content – including corn, sunflower, and safflower oils – trigger comparable effects.
“Soybean oil isn’t inherently evil,” said Deol. “But the quantities in which we consume it is triggering pathways our bodies didn’t evolve to handle.”
Although the researchers have no plans for human trials, they hope the findings will inform future studies and guide public health policy.
“It took 100 years from the first observed link between chewing tobacco and cancer to get warning labels on cigarettes,” Sladek noted. “We hope it won’t take that long for society to recognise the link between excessive soybean oil consumption and negative health effects.”
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