Study Reveals How Obesity in Pregnancy Triggers Liver Disorders in Offspring

The researchers found that offspring of obese mouse mothers developed fatty liver disease shortly after birth—even when fed a normal diet. The team discovered that metabolic products from the mother activate a transcription factor in Kupffer cells during pregnancy, reprogramming them to send signals that promote fat accumulation in the liver.

To test whether this reprogramming could be reversed, the researchers genetically removed the transcription factor during pregnancy. As a result, the offspring did not develop fatty liver disease, offering a promising direction for future treatment strategies. Whether this pathway can be targeted with medication remains to be seen, and follow-up studies are underway.

“This switch is a so-called transcription factor. It controls which genes are active in Kupffer cells,” said Mass, emphasizing the precision of this molecular mechanism. The implications are far-reaching: early changes in liver programming may set the stage for lifelong health challenges.

Reference: Huang, H., Balzer, N.R., Seep, L. et al. Kupffer cell programming by maternal obesity triggers fatty liver disease. Nature (2025). https://doi.org/10.1038/s41586-025-09190-w