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Platelets contribute significantly to fatty liver and liver cancer
Until recently, platelets, known in the technical sense as platelets, were only known as guarantors of blood clotting and wound healing. But researchers have now been able to show that these smallest cells in the blood are also crucially involved in the development of fatty liver, non-alcoholic fatty liver inflammation and liver cancer.
No effective drug therapy
Health experts say that non-alcoholic fatty liver is one of the most common chronic liver diseases in western industrialized nations and is also increasing rapidly in emerging countries. Around a third of Germans are affected. There is currently no effective drug therapy. However, everyone can do something about it themselves. Since the disease is often triggered by a lack of exercise and an unhealthy diet, a change in diet and more exercise are usually recommended for treatment.
Risk factors for fatty liver
The most important risk factors for fatty liver are overweight - especially in connection with excessive fat deposition in the abdomen - and type 2 diabetes.
However, nutrition and lack of exercise are only one aspect of the event, as a team of researchers led by Mathias Heikenwälder at the German Cancer Research Center (DKFZ) and colleagues led by Achim Weber from the University Hospital and the University of Zurich discovered.
Because for a fatty liver to grow into an inflammation, certain immune cells have to migrate into the liver. But what attracts them?
"We have now shown for the first time that platelets play a crucial role in this," Heikenwälder said in a message.
Platelets are known as guarantors of blood clotting and wound healing
Platelets, called platelets in technical terms, are the smallest cells in the blood. Until recently, they were known only as guarantors of blood clotting and wound healing.
But researchers are increasingly discovering that they are involved in numerous pathological processes and also in the development of cancer.
Heikenwälder and colleagues have now shown that platelets in the liver are increasingly found in mice on a high-fat diet. They observed similar things in people with non-alcohol-related fatty liver.
The results of the study were recently published in the journal "Nature Medicine".
Inflammation of the liver weakened
If the mice were treated with the anticoagulants aspirin and clopidogrel, which also act on the platelets, over a period of twelve months in addition to their fatty food, both the number of immigrated platelets and the number of inflammatory immune cells in the liver were reduced.
The researchers achieved the same effect when they gave their experimental animals another blood thinner that specifically only inhibits the function of platelets (ticagrelor).
"Although the mice became overweight, they had no fatty liver or liver cancer," said Heikenwälder.
The researchers identified Kupffer cells, special phagocytes (macrophages) of the liver, as responsible for attracting platelets into the liver.
It also seems to play a crucial role that the immigrant platelets dock with the Kupffer cells of the liver. This can happen via two different molecular “docking points”.
According to the experts, the glycoprotein GPIbα on the surface of the platelets plays a particularly important role in this docking maneuver.
If the scientists blocked GPIbα with an antibody, the number of messenger substances in the liver that attract inflammatory immune cells decreased. As a result, the inflammation of the liver also decreased.
New approaches for the therapy of the disease
The research team is not only on the trail of a better understanding of fatty liver with its work. "From our results, we now want to develop new approaches for the treatment of fatty liver, which we have already shown in the mice," said Heikenwälder.
It is conceivable to reduce the number of active blood platelets in fatty liver or to prevent them from sticking and thus preventing the recruitment of inflammatory immune cells. This could be achieved, for example, by using anticoagulants or antibodies against GPIbα.
In a pilot study, the scientists found that when people with fatty liver are treated with blood thinners, the amount of fat in the liver decreases, as does the size of the organ.
Heikenwälder has the vision of specifically influencing and protecting the liver as the central organ for metabolism.
"If we succeed in breaking the cycle of inflammatory processes, we can help affected people to lower their risk of fatty liver-induced liver cancer."
Effects on the entire metabolism
As the DKFZ explains in the message, fatty liver is increasingly stored in liver cells. Affected people usually do not notice this at first, but it is anything but harmless.
Because fatty liver can develop into liver inflammation with pathological changes, the so-called non-alcohol-related steatohepatitis (NASH), which in turn can lead to cirrhosis of the liver.
The cells of the metabolic organ perish, the liver scars and shrinks until it is no longer able to fulfill its task. At the same time, the risk of liver cancer is growing.
In addition, fatty liver affects the entire metabolism and increases the risk of type 2 diabetes and cardiovascular diseases. (ad)