Researchers at the University of California, Riverside report that fat-derived molecules called oxylipins, formed from linoleic acid in soybean oil, are linked to weight gain in mice on a high-fat diet. The work, published in the Journal of Lipid Research, suggests that these compounds can promote inflammation and alter liver metabolism, helping explain why soybean oil-rich diets appear more obesogenic than some other fats in animal studies.
Soybean oil, the most commonly used cooking oil in the United States and a staple in many processed foods, has been linked to obesity in mice through a newly described metabolic pathway, according to research from the University of California, Riverside published in the Journal of Lipid Research.
In the study, most mice fed a high‑fat diet rich in soybean oil gained substantial weight, while a separate group of genetically engineered, or transgenic, mice on the same diet were largely protected from this weight gain. The modified mice produced an alternative form of a liver protein called HNF4α, which affects hundreds of genes involved in fat metabolism and changes how the body handles linoleic acid, one of the primary fatty acids 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 UC Riverside biomedical scientist and corresponding author of the study, in comments released by the university.
The findings build on a 2015 UC Riverside study that found soybean oil to be more obesogenic than coconut oil in mice. "We've known since our 2015 study that soybean oil is more obesogenic than coconut oil," said Frances Sladek, a UC Riverside 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."
Inside the body, linoleic acid is broken down into compounds known as oxylipins. Excessive intake of linoleic acid can raise oxylipin levels, which are associated with inflammation and fat accumulation in animal and experimental studies. In the new mouse experiments, the transgenic animals produced far fewer oxylipins, had healthier liver tissue and showed better mitochondrial function, and these differences were associated with resistance to weight gain on the high‑fat soybean oil diet.
The researchers also narrowed the obesity‑linked molecules to specific oxylipins derived from both linoleic acid and alpha‑linolenic acid, another fatty acid present in soybean oil. These particular oxylipins were required for weight gain in normal mice on the soybean oil‑rich diet. However, the study found that oxylipins alone did not explain obesity risk: transgenic mice on a low‑fat diet still had elevated oxylipin levels but remained lean, indicating that additional dietary and metabolic factors must interact with these molecules to drive weight gain.
Further analysis showed that the transgenic mice had markedly lower activity of two enzyme families that convert linoleic acid into oxylipins. Similar enzymes are present in humans and other mammals, and their activity can vary with genetics, diet and other biological factors, according to the UC Riverside team.
The researchers reported that oxylipin levels in liver tissue, but not those circulating in the blood, correlated with body weight in the mice. That pattern suggests that standard blood tests may miss early, diet‑related metabolic changes that occur in the liver.
Over the past century, soybean oil consumption in the United States has increased roughly five‑fold, from about 2% of total calories to nearly 10%, according to data cited by the UC Riverside group. Although soybean oil itself contains no cholesterol, mice consuming the soybean oil‑rich diet in the study had higher cholesterol levels.
The team is now investigating how oxylipin formation leads to obesity and whether similar effects occur with other oils high in linoleic acid, including corn, sunflower and safflower oils. "Soybean oil isn't inherently evil," Sladek said. "But the quantities in which we consume it is triggering pathways our bodies didn't evolve to handle."
While no human trials are currently planned, the scientists say they hope their work will guide future human studies and inform nutrition policy discussions. Drawing a historical comparison, Sladek noted that "it took 100 years from the first observed link between chewing tobacco and cancer to get warning labels on cigarettes," and added that the team hopes it will not take as long for the health impacts of excessive soybean oil consumption to be fully recognized.
