Scientists have uncovered new clues about why soybean oil, the most widely consumed cooking oil in the U.S., contributes to significant weight gain in mice.
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New study reveals metabolic pathway linked to weight gain in mice.
Soybean oil is the most commonly used cooking oil in the United States and a frequent ingredient in processed foods, and research suggests it plays a role in promoting obesity in mice. Scientists are beginning to uncover the biological reasons behind this effect.
In a UC Riverside study, most mice fed a high-fat diet containing large amounts of soybean oil experienced notable weight gain. A separate group of genetically engineered mice did not. These modified mice produced a slightly different version of a liver protein that regulates hundreds of genes involved in fat metabolism. This altered protein also seems to affect how the body handles linoleic acid, the primary fatty acid found in 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 UCR biomedical scientist and corresponding author of the study published in the Journal of Lipid Research.
Credit: Sonia Deol/UCR
A Human Parallel: Two Forms of HNF4α
Humans also produce two forms of the liver protein HNF4α, although the less common version usually appears only in specific situations, including chronic disease or metabolic stress caused by fasting or alcoholic fatty liver. This difference, combined with factors such as age, sex, medication use, and genetic background, may clarify why some individuals respond more strongly than others to the metabolic influence of soybean oil.
The study builds on earlier work by UCR researchers linking soybean oil to weight gain. “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.”
Soybean oil consumption has increased alongside obesity in the U.S.
Humans also produce two forms of the liver protein HNF4α, although the less common version usually appears only in specific situations, including chronic disease or metabolic stress caused by fasting or alcoholic fatty liver. This difference, combined with factors such as age, sex, medication use, and genetic background, may clarify why some individuals respond more strongly than others to the metabolic influence of soybean oil.
The study builds on earlier work by UCR researchers linking soybean oil to weight gain. “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.”
Credit: Sonia Deol/UCR
Linoleic acid is transformed in the body into compounds known as oxylipins. When linoleic acid is consumed in large amounts, these oxylipins can rise to higher levels, and they have been linked to inflammation and the buildup of body fat.
In the study, the genetically engineered (transgenic) mice produced far fewer oxylipins and had healthier liver tissue even though they consumed the same high-fat soybean oil diet as the regular mice. They also showed improved mitochondrial activity, which may help account for why they did not gain as much weight.
Which Oxylipins Matter Most?
The researchers narrowed the obesity-linked compounds down 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 in regular mice.
However, transgenic mice on a low-fat diet also had elevated oxylipins without becoming obese, suggesting that the presence of these molecules alone isn’t enough, and other metabolic factors likely contribute to obesity.
Additional analysis revealed that the altered mice had much lower levels of two key enzyme families responsible for converting linoleic acid into oxylipins. Notably, the function of these enzymes is highly conserved across all mammals, including humans. Levels of these enzymes are known to be highly variable based on genetics, diet, and other factors.
The team also noted that only oxylipin levels in the liver, and not the in the blood, correlated with body weight. This means common blood tests may not reliably capture early metabolic changes linked to diet.
Linoleic acid is transformed in the body into compounds known as oxylipins. When linoleic acid is consumed in large amounts, these oxylipins can rise to higher levels, and they have been linked to inflammation and the buildup of body fat.
In the study, the genetically engineered (transgenic) mice produced far fewer oxylipins and had healthier liver tissue even though they consumed the same high-fat soybean oil diet as the regular mice. They also showed improved mitochondrial activity, which may help account for why they did not gain as much weight.
Which Oxylipins Matter Most?
The researchers narrowed the obesity-linked compounds down 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 in regular mice.
However, transgenic mice on a low-fat diet also had elevated oxylipins without becoming obese, suggesting that the presence of these molecules alone isn’t enough, and other metabolic factors likely contribute to obesity.
Additional analysis revealed that the altered mice had much lower levels of two key enzyme families responsible for converting linoleic acid into oxylipins. Notably, the function of these enzymes is highly conserved across all mammals, including humans. Levels of these enzymes are known to be highly variable based on genetics, diet, and other factors.
The team also noted that only oxylipin levels in the liver, and not the in the blood, correlated with body weight. This means common blood tests may not reliably capture early metabolic changes linked to diet.
Rising Consumption and Health Concerns
Soybean oil consumption in the U.S. has increased five-fold in the past century, from about 2% of total calories to nearly 10% today. Although soybeans are a rich source of plant-based protein and their oil contains no cholesterol, the overconsumption of linoleic acid, including from ultra-processed foods, may be fueling chronic metabolic conditions.
Additionally, despite the lack of cholesterol in the oil, the UCR study found that consumption of soybean oil is associated with higher cholesterol levels in mice.
The researchers are now exploring how oxylipin formation causes weight gain, and whether similar effects occur with other oils high in linoleic acid, such as corn, sunflower, and safflower.
“Soybean oil isn’t inherently evil,” Sladek said. “But the quantities in which we consume it are triggering pathways our bodies didn’t evolve to handle.”
Though no human trials are planned, the team hopes these findings will help guide future research and inform nutrition policy.
“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.”
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