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The fat metabolism can now be monitored down to the individual liver cell



  Liver cells full of fat

Image of liver cells full of fat droplets (orange). The cell nuclei are shown in blue. Picture credits: © K. Piotrowitz / AG Thiele

Tracking of "Fat Packages" in the Body: Researchers at the University of Bonn have shown that highly sensitive methods can "track" lipid metabolism.

Nothing works without fat The body: These substances serve as sources of energy and important building blocks ̵

1; also for the envelope of living cells. Numerous disorders are associated with disorders of lipid metabolism such as obesity or cancer. Researchers at the LIMES Institute of the University of Bonn are now demonstrating how the lipid metabolism can be monitored with maximum sensitivity right down to the individual liver cell of a mouse. This opens up various possibilities, for example minimizing the side effects of new drugs on fat metabolism. The scientists published their study on October 14, 2019 in the journal Nature Methods .

Many people think of the padding of their stomach or hips when they hear the term "body fat" No human could survive without lipids, as these substances are called in chemistry, "says Prof. Dr. med. Christoph Thiele from the LIMES Institute of the University of Bonn. Because fats are important energy stores. For example, if fat metabolism in cancer patients is disturbed, it results in dramatic weight loss. In addition, lipids often serve as building blocks for the envelope of living cells, such as brain cells. Therefore, disorders can also lead to neurological diseases.

  Klaus Wunderling, Philipp Leyendecker and Prof. Dr. med. Christoph Thiele

In the lab: (from left) Klaus Wunderling, Philipp Leyendecker and Prof. Dr. med. Christoph Thiele at the LIMES Institute of the University of Bonn. Photo credits: © Photo: Barbara Frommann / University of Bonn

Scientists are therefore looking for methods that enable them to track the path from ingesting fats through metabolism in the body to elimination with a kind of "tracking" procedure – Similar to A Discontinued Package that can be tracked en route to your destination. So far, the researchers used radioactive substances, fluorescent dyes or heavy isotopes of hydrogen-2 (deuterium) to mark the "fat particles".

"The problem with this is that the labeled compounds can not be completely differentiated from the unlabeled compounds," explains Thiele. This means that only a few labeled main compounds are detectable and quite large amounts of substance are required.

Decay reactions lead to strong signals during the measurement.

Together with his teammates Klaus Wunderling and Philipp Leyendecker, the biochemist has now shown how fats in the body of mice can be traced using a much more sensitive and effective method. They added to the liver cells of the mice fatty acids which were labeled with an additional triple bond, a so-called alkyne group. Subsequently, the metabolites are bound to special so-called reporter molecules. In a further step, the compounds collided with gas molecules while their weight was measured in the mass spectrometer, causing them to decompose into certain substances on which the labels eventually became visible. "This decay reaction produces very strong signals for the labeled lipids in the mass spectrometer," said Thiele. This allows a clearer distinction between labeled and unlabelled lipids and the measurements are about 1000 times more sensitive than with conventional methods. It also goes much faster: the results take minutes instead of hours.

"Around 100 differently labeled lipids can actually be traced back to individual liver cells," explains the biochemist. This makes it possible to examine in detail both the normal metabolic pathway and pathological deviations. Examination of mouse liver cells was a natural choice for the researchers, as the liver is the "main junction" for lipid metabolism.

However, this method is not yet suitable for human nutrition experiments. "We still do not know exactly what the fatty acids coupled to alkyne groups in the human body do when ingested with food," says Thiele. Nevertheless, the researcher is convinced that this method could be used to investigate and possibly significantly reduce the side effects of drugs on lipid metabolism. Since human consumption trials are currently not possible, the side effects could be tested on cell cultures or organoids. Thiele: "This makes it easy to see how the lipid metabolism is changed by the active ingredients."

Nature Methods .
DOI: 10.1038 / s41592-019-0593-6


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