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Soybean oil, the most widely consumed cooking oil in the United States and a key ingredient in processed foods, contributes to obesity — at least in mice — through a mechanism scientists are only now beginning to understand.
In an experiment conducted at the University of California, Riverside (UCR), most mice fed a high-fat diet rich in soybean oil gained significant weight. However, a group of genetically modified mice did not put on the same weight. These mice produced a slightly different form of a liver protein that influences hundreds of genes linked to fat metabolism. This protein also appears to alter how the body processes linoleic acid, a major component of soybean oil.
"This may be a first step toward understanding why some people gain weight more easily than others on a diet rich in soybean oil," said Sonia Deol, a biomedical scientist at UC Riverside and corresponding author of the study, published in the Journal of Lipid Research.
In humans, both versions of the liver protein (HNF4α) exist, but the alternative form is typically produced only under certain conditions, such as chronic illness, metabolic stress from fasting, or alcoholic fatty liver disease. This variation, along with differences in age, sex, medication and genetics, may help explain why some people are more susceptible than others to the metabolic effects of soybean oil.
The study builds on earlier work by university researchers linking soybean oil to weight gain. "We've known since our 2015 study that soybean oil is more obesity-inducing than coconut oil. But now we have the clearest evidence yet that the cause isn't the oil itself, or even linoleic acid. It's what the fat turns into inside the body," said Frances Sladek, professor of cell biology at the university.
Linoleic acid is converted into molecules called oxylipins. Excessive consumption of linoleic acid can lead to elevated levels of oxylipins, which are linked to inflammation and fat accumulation.
The genetically modified mice in the study had significantly fewer oxylipins and showed healthier livers despite eating the same high-fat, soybean oil-rich diet as the ordinary mice. Notably, they also showed enhanced mitochondrial function, which may help explain their resistance to weight gain.
The researchers narrowed down the compounds linked to obesity to specific types of oxylipins derived from linoleic acid and alpha-linolenic acid, another fatty acid found in soybean oil. These oxylipins were necessary for weight gain to occur in the ordinary mice.
However, the genetically modified mice on a low-fat diet also had elevated oxylipin levels without becoming obese, suggesting that the presence of these molecules alone is not sufficient, and that other metabolic factors likely contribute to obesity.
Further analysis revealed that the modified mice had significantly lower levels of two major families of enzymes responsible for converting linoleic acid into oxylipins. Notably, the function of these enzymes is highly conserved across all mammals, including humans. These enzyme levels are known to vary considerably based on genetics, diet and other factors.
The team also observed that oxylipin levels in the liver alone, not in the blood, correlated with body weight. This means common blood tests may not reliably capture early diet-related metabolic changes.
Soybean oil consumption in the United States has increased fivefold over the past century, from about 2% of total calorie intake to nearly 10% today. Although soybeans are a rich source of plant protein and the oil is cholesterol-free, excessive consumption of linoleic acid, including from ultra-processed foods, may fuel chronic metabolic conditions.
In addition, despite the oil being cholesterol-free, the UC Riverside study found that soybean oil consumption was associated with higher cholesterol levels in mice.
Researchers are now exploring how oxylipin formation causes weight gain, and whether similar effects occur with other oils rich in linoleic acid, such as corn, sunflower and safflower oils.
"Soybean oil isn't inherently evil," Deol said. "But the amounts we're consuming it in are triggering pathways our bodies never evolved to handle."
Although no human trials are currently planned, the team hopes the findings will help guide future research and inform nutrition policy.
Sladek concluded: "It took 100 years from the first observed link between chewing tobacco and cancer to putting warning labels on cigarettes. We hope it doesn't take that long for society to recognise the link between excessive soybean oil consumption and negative health effects."
Source: University of California, Riverside