Study Reveals How Obesity in Pregnancy Triggers Liver Disorders in Offspring

Children born to obese mothers may face an increased risk of developing metabolic disorders, even when they follow a healthy diet themselves. A new study published in Nature by researchers at the University of Bonn offers a compelling explanation: in obese mice, maternal obesity reprograms immune cells in the embryo’s liver, causing lasting disruptions to metabolic function in the offspring.

The study focused on Kupffer cells, a specialized type of macrophage that takes up permanent residence in the liver during embryonic development. These cells play a critical role not only in immune defense but also in regulating liver metabolism. “They instruct the surrounding liver cells on what to do,” explains Prof. Dr. Elvira Mass from the LIMES Institute at the University of Bonn. “In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”

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