Microplastics impair liver function and increase fat in mice

Microplastics appear capable of significantly impairing the function of phagocytes in the liver, at least in mice. In turn, this disrupts the metabolism of this vital organ and increases the build-up of fat inside it. These are the key findings from a joint German-Austrian study led by the University of Bonn, details of which have now been published in the journal "Nature Metabolism."

Phagocytes, literally "eating cells", or "macrophages" to give them their scientific name, are immune cells that reside in virtually every organ of the body. They play an important protective role, looking out for bacteria, diseased cells and traces of foreign matter, engulfing them and breaking them down into their component parts. In addition, they help the organs they live in to function properly.

From working with cell cultures, we've known for several years that macrophages also take up microplastics. We wanted to know whether that's also the case in a living organism and, if so, what effect it has."

Professor Elvira Mass, LIMES Institute, University of Bonn

To this end, Mass joined forces with a number of other research groups from the University of Bonn and the University Hospital Bonn (UKB) to focus on a specific group of macrophages known as Kupffer cells. These reside in the sinusoids, the smallest blood vessels of the liver, where they monitor the blood arriving from the gut. Plastic particles that humans or animals swallow and that enter the bloodstream via the gut therefore have to pass by them.

We may ingest up to a credit card's worth of plastic every week

And we are talking about quite a lot of particles: Experts estimate that adults ingest up to five grams of plastic a week, which is about the weight of a credit card. With young mice tipping the scale at a mere 20 grams, the researchers scaled down the dose accordingly. "We administered microplastics to the animals orally once a week," says Mass, who is also speaker for the Life and Health Transdisciplinary Research Area (TRA) and a member of the steering committee for the ImmunoSensation3 Cluster of Excellence. The individual particles were about the same diameter as an average bacterium.

Twelve weeks later, the researchers examined the animals. "We were able to show that the Kupffer cells had taken up large amounts of microplastics," explains Dr. Nikola Makdissi, who ran many of the experiments with his colleague Dr. Maria Francesca Viola. Macrophages usually digest what they engulf and recycle its component parts. Plastic, however, cannot be broken down and instead clogs up the macrophages' "stomachs", the so-called lysosomes. "On the one hand, this means they can no longer take up pathogens or defective cells," Makdissi explains. "On the other hand, they lack important building blocks that they need for their metabolism."

Microplastics clog up the macrophages' "stomachs"

The macrophages react by producing more apolipoproteins, proteins that normally help to transport fats in the body. Here, they act as a kind of molecular stress signal. "The surrounding liver cells detect this signal and respond by storing more fat," Mass says. In other words, the disruption to the macrophages' function in turn leads to a metabolic imbalance in the liver.

Plastic particles that are a similar size to bacteria appear to be particularly harmful to the liver. When the researchers instead gave the mice particles that were ten times smaller, they observed different effects: The "clogging" of the macrophages was now much less pronounced, and liver metabolism remained largely unchanged. Instead, the plastic nanoparticles accumulated in the brown adipose tissue ("brown fat"). Unlike its white counterpart, brown adipose tissue does not primarily store fat but "burns" it to generate heat.

In the mice, the nanoplastics activated the brown adipose tissue and stimulated this heat production. The researchers now want to investigate this effect in more detail.

Institutions involved and funding:

The University of Bonn and University Hospital Bonn were involved in the study alongside the Tulln campus of BOKU University (Austria), Friedrich-Alexander-Universität Erlangen-Nürnberg, the University of Vienna (Austria) and the University of Hamburg. The work was funded by several organizations, including the German Research Foundation, the European Research Council, the Jürgen Manchot Stiftung, the Boehringer Ingelheim Fonds, the German Academic Scholarship Foundation, the European Molecular Biology Organization and the Austrian Science Fund.