Soybean oil, the most commonly used cooking oil in the United States, has been linked to obesity in mice according to new research from the University of California, Riverside. The study, published in the Journal of Lipid Research, explored how a high-fat diet rich in soybean oil affected weight gain and liver health.
Researchers found that most mice on a soybean oil-rich diet gained significant weight. However, a group of genetically engineered mice did not experience the same weight gain. These modified mice produced an alternative form of the liver protein HNF4α, which influences genes involved in fat metabolism and alters how the body processes linoleic acid—a key component of soybean oil.
“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 biomedical scientist at UC Riverside and corresponding author of the study.
Both forms of HNF4α exist in humans, but one is usually only present during certain conditions such as chronic illness or metabolic stress. Differences in this protein variant—as well as factors like age, sex, medications, and genetics—could help explain individual susceptibility to the effects of soybean oil.
Frances Sladek, a UC Riverside professor of cell biology who participated in the research, 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.”
The study found that linoleic acid is converted into oxylipins—molecules associated with inflammation and fat accumulation. Mice with genetic modifications had lower levels of oxylipins and healthier livers despite eating a high-fat soybean oil diet. They also showed improved mitochondrial function.
The researchers identified specific oxylipins derived from both linoleic acid and alpha-linolenic acid as necessary for weight gain in regular mice. Yet transgenic mice on low-fat diets also had elevated oxylipins without becoming obese, indicating that other metabolic factors are likely involved.
Analysis revealed that altered mice had much lower levels of two enzyme families responsible for converting linoleic acid into oxylipins. These enzymes are highly conserved across mammals—including humans—and their activity varies based on genetics and diet.
The team observed that only liver oxylipin levels correlated with body weight; blood tests did not show this link. This suggests common blood tests may not reliably detect early metabolic changes related to dietary intake.
Over the past century, U.S. consumption of soybean oil has increased five-fold—from about 2% to nearly 10% of total calories consumed by Americans today. While soybeans provide plant-based protein and their oil contains no cholesterol, overconsumption of linoleic acid from processed foods could contribute to chronic metabolic diseases.
Despite its lack of cholesterol content, researchers noted an association between soybean oil consumption and higher cholesterol levels in mice.
Future studies will investigate whether similar effects occur with other oils high in linoleic acid—such as corn, sunflower, and safflower oils—and examine how oxylipin formation leads to weight gain.
“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 no immediate plans for human trials, researchers hope these findings will inform future research efforts and guide nutrition policy decisions.
“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.”
