Children of overweight mothers often develop metabolic disorders such as a fatty liver, even if they eat a healthy diet after birth. A recent study by the University of Bonn now provides new explanations for this phenomenon. According to the study, certain cells in the liver of the embryo, so-called Kupffer cells, are permanently reprogrammed in obese mice during pregnancy. These macrophages are part of the innate immune system and not only perform defense functions in the liver, but also control the activity of the surrounding liver cells.

The researchers were able to show that the offspring of overweight mother animals developed a fatty liver shortly after birth – regardless of how they were fed. The cause is a molecular reprogramming of the Kupffer cells, which is triggered during embryonic development by metabolic products from the mother. These cells then release signals that instruct the liver cells to absorb more fat. Central to this reprogramming is a so-called transcription factor, which acts as a molecular switch and controls which genes are read in the Kupffer cells.

If the researchers genetically removed this switch during pregnancy, the offspring did not develop a fatty liver. The study suggests that this mechanism could also play a role in humans. The reprogramming of Kupffer cells has far-reaching consequences: The resulting fatty liver is accompanied by inflammatory reactions that can lead to the death of liver cells and the formation of connective tissue (fibrosis). As the disease progresses, there is a risk of loss of liver function and an increased risk of liver cancer.

The results show that many human diseases can already be established very early in life. In addition to the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE) and the Universities of Vienna, Ghent and Shanghai were involved in the study. The work was funded by the German Research Foundation, the European Research Council, the Jürgen Manchot Foundation, the Boehringer Ingelheim Fund and the European Molecular Biology Organization.

Original Paper:

Kupffer cell programming by maternal obesity triggers fatty liver disease | Nature

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