Obese mothers may trigger lifelong liver damage in babies

Even before a baby’s birth, a lot has already happened. Organs are built, immune cells settle in, and tiny instructions shape the body for life outside.

But in babies born to higher-weight mothers, those early instructions can affect the liver – and sometimes, they carry a cost.

Children born to higher-weight mothers often face metabolic challenges later in life. Even when they eat healthy, their livers may tell a different story. Scientists at the University of Bonn asked a big question: why? What’s going on in the womb that leaves such a lasting mark?

Turns out, it’s not just fat or food. It’s communication. A certain type of immune cell in the liver, the Kupffer cell, starts singing a different tune when the mother is considered to be obese. And the rest of the liver listens.

Obese pregnancy rewires liver cells

Kupffer cells aren’t just janitors cleaning up dying cells, they lead. During development, they enter the liver early and stay for life. They send signals, guide metabolism, and help keep balance.

“But these Kupffer cells also act as conductors,” said Professor Dr. Elvira Mass from the LIMES Institute at the University of Bonn. “They instruct the surrounding liver cells on what to do. In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”

But in the offspring of heavier-weight mothers, these instructions change. Something tweaks the conductor’s baton. The Kupffer cells tell liver cells to soak up fat. Fat they don’t need. Fat that eventually causes disease.

Liver gets fatty even without bad diet

In experiments with mice, the team saw a strange thing. Even pups fed a normal diet developed fatty livers if their mothers were classified as obese. That raised a red flag.

“We were able to show that the offspring of obese mothers frequently developed a fatty liver shortly after birth,” said study co-author Dr. Hao Huang from the University of Bonn. “And this happened even when the young animals were fed a completely normal diet.”

How? The Kupffer cells got reprogrammed. They remembered the womb. They carried forward a message: hold onto fat. Even when there was no need.

“Figuratively speaking, they no longer conduct one of Beethoven’s symphonies but rather a piece by Vivaldi,” said Huang.

Pregnancy triggers lasting liver change

What changes these cells? Metabolic signals from the mother. They flip a molecular switch in the Kupffer cells, a switch called HIF1α. Once flipped, this switch changes how the cells behave long term.

These Kupffer cells no longer burn fuel like before. They shift from efficient energy use to a fast and dirty mode: glycolysis. That shift activates genes that push the liver toward storing fat.

When the researchers removed this switch during pregnancy, something amazing happened. No fatty liver. The offspring grew up healthy. Their livers stayed lean.

Cells ignite disease after birth

There’s more. These reprogrammed Kupffer cells start churning out proteins like APOE and APOA1. These are usually part of lipid transport, but here they act like little fat magnets.

In the lab, when scientists exposed liver cells to these proteins, fat started to pile up fast.

Within four hours, fat droplets formed. That’s how strong these signals are. And they don’t just cause fat buildup. They stir inflammation too.

Fat plus inflammation equals trouble. Over time, inflamed livers develop scars. Fibrosis. That damage limits function and can lead to cancer. All from a signal passed on before birth.

Liver carries lifelong memory of obesity

The team went deeper. They studied the epigenetics, how genes are packaged and read. Kupffer cells from heavier-weight pregnancies looked different at that level too.

Their chromatin, the wrapping around DNA, had changed. That meant different genes stayed active, even long after birth. The cells remembered. They carried a permanent record of their developmental environment.

Clusters of these programmed Kupffer cells appeared. They glowed with active genes for lipid metabolism, inflammation, and immune regulation. None of this happened in control mice.

Cell reset soon after birth

Maybe. The researchers tried two things. First, they wiped out Kupffer cells right after birth and let new ones grow in. The new cells didn’t carry the memory. The mice didn’t develop fatty liver.

Second, they turned off the HIF1α switch during pregnancy. Again, the liver stayed healthy. That gives hope.

The idea that we could reset or avoid these developmental instructions opens a new path. Instead of treating liver disease years later, we could prevent it before birth or shortly after.

Obesity likely impacts human babies

While the study used mice, the implications don’t stop there. Maternal obesity in humans is rising. So is childhood fatty liver disease. The patterns match. It’s likely that a similar mechanism operates in people too.

“It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage,” says Mass. “Our study is one of the few to explain in detail how this early programming can happen.”

This isn’t just a mouse story. It’s a message about how deeply early life matters. About how immune cells, once programmed, can carry out instructions that last for decades.

Resetting early disease signals

This project brought together teams from Bonn, Vienna, Ghent, and Shanghai. Funding came from major European and German research groups.

Together, they mapped a hidden pathway from maternal obesity to liver disease in the next generation.

For now, it’s a warning. But it could become an opportunity. If researchers can find ways to reprogram or reset Kupffer cells, they might cut off fatty liver at its source.

The study is published in the journal Nature.

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