Eating a high-fat diet doesn’t just lead to weight gain—it can trigger a cascade of harmful changes inside your body, especially at the cellular level.
A new study led by researchers at MIT has uncovered how such diets disrupt key enzymes in cells, setting the stage for insulin resistance, oxidative stress, and metabolic dysfunction.
The good news?
Some of this damage may be reversible with antioxidants.
The research, published in Molecular Cell, focused on how high-fat diets affect enzymes that control metabolism—the process of converting food into energy and essential molecules.
The scientists, led by Dr. Tigist Tamir, found that in mice, hundreds of enzymes were altered by a high-fat diet, leading to an imbalance in the body’s redox state.
In simple terms, cells started producing more harmful molecules called reactive oxygen species (ROS) than they could safely manage. This redox imbalance is closely linked to weight gain, insulin resistance, and increased risk for chronic diseases like diabetes.
One key finding was how enzymes are affected by a process called phosphorylation—when a small molecule called a phosphate group is added to them.
This process acts like a switch, turning enzyme activity on or off depending on the body’s needs. In a high-fat environment, many enzymes undergo abnormal phosphorylation, which disrupts their ability to function properly.
Some of the most affected enzymes are central to sugar and fat metabolism, including IDH1 and AKR1C1. Others play roles in controlling the levels of ROS. When these enzymes malfunction, cells experience stress and struggle to keep up with the demands of a high-fat diet. Interestingly, these changes were far more severe in male mice than in females, who appeared to have better biological mechanisms for dealing with fat overload.
To see if the damage could be reversed, the researchers gave some of the mice an antioxidant called BHA along with their high-fat diet.
The results were striking. The mice given BHA gained less weight and avoided becoming prediabetic, even though they continued eating fatty foods. Their cells also showed a healthier balance of enzyme activity and lower levels of oxidative stress.
Dr. Tamir, now a professor at the University of North Carolina, plans to investigate whether antioxidants could be a practical way to prevent or treat obesity-related diseases in humans.
While this study was done in mice, it adds to growing evidence that what we eat can rapidly change how our cells function—and that it might be possible to counteract some of the damage with the right interventions.
