Healthcare (Commonwealth Union) – Soybean oil is a major cooking oil across the world. and a key ingredient in many processed foods. The oil appears to drive weight gain, at least in mice, through a biological pathway researchers are only now beginning to unravel.
In a University of California, Riverside (UCR) study, most mice fed a high-fat diet heavy in soybean oil became noticeably heavier. But a second group of genetically modified mice did not. These engineered mice produced a slightly altered version of a liver protein that regulates hundreds of genes involved in fat processing, and this variant seems to shift how the body handles linoleic acid, one of soybean oil’s main components.
Sonia Deol, who is a biomedical researcher at UCR and the study’s corresponding author, whose findings appear in the Journal of Lipid Research indicated that it could be the first clue to understanding why some individuals put on weight more easily than others when consuming a diet high in soybean oil.
Humans have both forms of the liver protein HNF4α, but the alternative version is usually generated only under certain conditions — such as chronic disease, metabolic stress from fasting, or alcohol-related fatty liver. Differences in which form is produced, combined with factors like age, sex, genetic background, and medication use, may help explain why some people are more sensitive than others to the metabolic impact of soybean oil.
The findings have been built on a foundation laid by work on prior occasions by UCR researchers that connect soybean oil to weight gain. “We’ve known since our 2015 study that soybean oil is more obesogenic than coconut oil,” added Frances Sladek, who is 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.”
Linoleic acid breaks down into compounds known as oxylipins. When someone consumes too much linoleic acid, the body produces higher levels of these oxylipins, which have been linked to inflammation and the buildup of body fat.
In the study, the genetically modified mice had far fewer oxylipins in their systems and maintained healthier liver function, even though they ate the same high-fat soybean-oil diet as the standard mice. They also had better-performing mitochondria, which could help explain why they didn’t put on extra weight.
The researchers pinpointed the compounds tied to obesity as certain oxylipins formed from both linoleic acid and alpha-linolenic acid, another fatty acid present in soybean oil. These specific oxylipins were essential for weight gain in the normal mice.
Interestingly, the transgenic mice on a low-fat diet also showed high oxylipin levels without becoming overweight, implying that oxylipins alone don’t cause obesity and that other metabolic processes are likely involved.
Further analysis showed that the genetically modified mice had significantly reduced levels of two major enzyme families that convert linoleic acid into oxylipins. These enzymes are notably well-conserved across all mammals, including humans, and their levels can vary widely due to genetics, diet, and other factors.
The researchers also observed that only oxylipin levels in the liver—not in the bloodstream—were linked to body weight. This suggests that standard blood tests may not effectively detect early metabolic changes triggered by diet.
In the U.S., soybean oil consumption has surged five-fold over the past 100 years, rising from roughly 2% of total calories to nearly 10% today. While soybeans are a valuable source of plant-based protein and the oil contains no cholesterol, excessive intake of linoleic acid—especially from ultra-processed foods—may contribute to chronic metabolic problems.
Interestingly, even though soybean oil is cholesterol-free, the UCR study found that mice consuming it still showed increased cholesterol levels.
The team is now investigating how oxylipin production leads to weight gain and whether similar effects occur with other oils rich in linoleic acid, including corn, sunflower, and safflower oil.
