A new study from the University of Bonn, published in Nature, explains why children of obese mothers face a higher risk of metabolic disorders, even with a healthy diet. The research focuses on Kupffer cells, liver-resident macrophages that develop during embryogenesis and play a key role in maintaining liver metabolism. These cells act as "conductors," instructing surrounding liver cells to ensure the liver's proper metabolic function.

Mouse experiments show that maternal obesity reprograms Kupffer cells during embryonic development, altering their function long-term. These reprogrammed cells persist into adulthood and send molecular signals that instruct liver cells to take up more fat, leading to a fatty liver disease in the offspring. This mechanism is controlled by a "molecular switch," a transcription factor, in the Kupffer cells. Genetically removing this switch prevents fatty liver development in the offspring.

Prof. Dr. Elvira Mass from the LIMES Institute at the University of Bonn emphasizes the broad significance, stating that "It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage". The findings open new avenues for preventing metabolic diseases and investigating potential drug targets in future studies.

Participating institutes and funding:

This project was a joint effort of the SFB 1454 „Metaflammation and Celluar Programming”, involving various laboratories. In addition to the Mass Lab, the Schultze Lab, the Beyer Lab, the Thiele Lab, the Meissner Lab, the Hasenauer Lab and the Wachten Lab were also contributors. This highlights the collaborative nature of the SFB in driving forward research.

In addition to the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the University of Vienna (Austria), Ghent University (Belgium), and Shanghai University (China) were involved in the study. The research was supported by the German Research Foundation (DFG, in particular SFB 1454 Metaflammation), the European Research Council (ERC), the Jürgen Manchot Foundation, the Boehringer Ingelheim Fonds and the European Molecular Biology Organization (EMBO).

More information you can find here

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Original Publication:

Hao Huang et al.: Kupffer cell programming by maternal obesity triggers fatty liver disease; Nature; DOI: 10.1038/s41586-025-09190-w

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