Soybean oil, which is the most commonly used cooking oil in the United States, has been linked to obesity in mice through mechanisms that researchers at UC Riverside are beginning to clarify. The study found that most mice fed a high-fat diet rich in soybean oil gained significant weight. However, genetically engineered mice with a slightly different form of a liver protein did not gain as much weight. This protein affects many genes involved in fat metabolism and changes how the body processes linoleic acid, a major part of soybean oil.
Sonia Deol, a biomedical scientist at UC Riverside and corresponding author of the study published in the Journal of Lipid Research, said, “This may be the first step toward understanding why some people gain weight more easily than others on a diet high in soybean oil.”
In humans, both versions of the liver protein HNF4α exist. The alternative form is usually produced only under certain conditions such as chronic illness or metabolic stress from fasting or alcoholic fatty liver disease. Differences related to age, sex, medications, and genetics may also influence how people respond metabolically to soybean oil.
The research builds on earlier findings by UC Riverside scientists who previously reported that soybean oil causes more weight gain than coconut oil. Frances Sladek, professor of cell biology at UC Riverside, said: “We’ve known since our 2015 study that soybean oil is more obesogenic than coconut oil. 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.”
Linoleic acid from soybean oil converts into oxylipins—molecules linked to inflammation and fat buildup when consumed excessively. In this study, transgenic mice had fewer oxylipins and healthier livers despite eating a high-fat soybean oil diet similar to regular mice. They also showed better mitochondrial function.
Researchers identified specific types of oxylipins derived from linoleic acid and alpha-linolenic acid as necessary for weight gain in regular mice. However, transgenic mice on low-fat diets had elevated oxylipins without becoming obese. This suggests other metabolic factors play roles in obesity beyond just these molecules.
Further analysis showed altered mice had lower levels of two enzyme families responsible for converting linoleic acid into oxylipins—enzymes present across all mammals including humans and known to vary based on genetics and diet.
The team found that only liver oxylipin levels—not those measured in blood—were associated with body weight changes. As a result, standard blood tests might not detect early metabolic shifts caused by dietary fats.
Over the past century, U.S. consumption of soybean oil has risen significantly—from about 2% to nearly 10% of total calories—largely due to its presence in processed foods. While soybeans are valued for plant-based protein and their oil contains no cholesterol, excessive intake of linoleic acid may contribute to chronic health problems.
Despite having no cholesterol itself, increased consumption of soybean oil was linked with higher cholesterol levels in mice according to UC Riverside’s findings.
Researchers plan further studies on how oxylipin formation leads to weight gain and whether similar effects occur with other oils high in linoleic acid like corn or sunflower oils.
“Soybean oil isn’t inherently evil,” Deol said. “But the quantities in which we consume it is triggering pathways our bodies didn’t evolve to handle.”
Although there are currently no plans for human trials based on this research, scientists hope their work will inform future studies and shape nutrition guidelines.
“It took 100 years from the first observed link between chewing tobacco and cancer to get warning labels on cigarettes,” Sladek said. “We hope it won’t take that long for society to recognize the link between excessive soybean oil consumption and negative health effects.”
