Study Shows How Antioxidants May Undo High-Fat Diet Damage

Study showed that these changes led to insulin resistance and the accumulation of reactive oxygen species—damaging molecules that indicate cellular stress. Males were found to be more affected than females, who compensated more effectively for the high-fat diet.

“Under metabolic stress conditions, enzymes can be affected to produce a more harmful state than what was initially there,” said Tamir. "Then what we've shown with the antioxidant study is that you can bring them to a different state that is less dysfunctional."

However, when the researchers introduced the antioxidant BHA alongside the high-fat diet, they saw a dramatic reduction in weight gain and prediabetic symptoms. “They’re experiencing a lot of metabolic dysfunction, but if you co-administer something that counters that, then they have enough reserve to maintain some sort of normalcy,” Tamir added.

The findings point to the potential of antioxidant therapies in mitigating metabolic damage caused by unhealthy diets. Tamir now plans to explore whether such treatments could be used to prevent or manage obesity-related disorders in humans.

Reference: Tigist Y. Tamir, Shreya Chaudhary, Annie X. Li, Sonia E. Trojan, Cameron T. Flower, Paula Vo, Yufei Cui, Jeffrey C. Davis, Rachit Mukkamala, Francesca N. Venditti, Alissandra L. Hillis, Alex Toker, Matthew G. Vander Heiden, Jessica B. Spinelli, Norman J. Kennedy, Roger J. Davis, Forest M. White. Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity. Molecular Cell, 2025; DOI: 10.1016/j.molcel.2025.05.007