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Altering liver's fat metabolism could help prevent diabetes without dietary changes

Altering liver's fat metabolis...
Altering the fat metabolism in the liver could reduce the chances of diabetes even while still eating a high-fat diet
Altering the fat metabolism in the liver could reduce the chances of diabetes even while still eating a high-fat diet
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(Left) Liver cells with high levels of fat deposits, compared to those (right) that have had ceramide synthase 6 blocked, which reduces the fat build-up in the liver, despite eating the same diet
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(Left) Liver cells with high levels of fat deposits, compared to those (right) that have had ceramide synthase 6 blocked, which reduces the fat build-up in the liver, despite eating the same diet
Altering the fat metabolism in the liver could reduce the chances of diabetes even while still eating a high-fat diet
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Altering the fat metabolism in the liver could reduce the chances of diabetes even while still eating a high-fat diet

No matter what the latest fad diet tells us to do, we already know the general gist of how to stay healthy – eating too much sugar and fat leads to weight gain and metabolic diseases. But what if you could stay healthier without changing your diet? In mouse tests conducted at the Max Planck Institute for Metabolism Research, researchers have now found a way to alter the fat metabolism in the liver, reducing the chances of diabetes without changing a high-fat diet.

Our bodies store fat in adipose tissue, but after eating high amounts of the stuff over a long period of time it begins to build up in more important places like the liver. That in turn can lead to fatty liver disease, which can then reduce the body's response to insulin and eventually bring on type 2 diabetes.

A group of fats known as ceramides have long been associated with these metabolic diseases, and plenty of research has in the past focused on lowering their levels by blocking the proteins that create them – ceramide synthases. Unfortunately, it hasn't always gone to plan.

"Other research groups have already shown that blocking ceramide production in mice prevents the development of insulin resistance," says Philipp Hammerschmidt, first author of the new study. "However, this is associated with a large number of side effects. If, for example, ceramide synthesis is completely inhibited it can adversely affect the development of the animals."

So the researchers tried to get more specific. Since ceramide is created by several different synthases, the team investigated which ones contribute to insulin resistance. In mouse tests, the team found that the ceramide molecules accumulating in the liver tended to be of a certain length, which indicated that they were being created by ceramide synthases 5 and 6.

(Left) Liver cells with high levels of fat deposits, compared to those (right) that have had ceramide synthase 6 blocked, which reduces the fat build-up in the liver, despite eating the same diet
(Left) Liver cells with high levels of fat deposits, compared to those (right) that have had ceramide synthase 6 blocked, which reduces the fat build-up in the liver, despite eating the same diet

Although the ceramides themselves looked identical, switching off each synthase in turn produced very different effects. Nothing changed when ceramide synthase 5 was blocked, but when they did the same to ceramide synthase 6, the mice stayed slimmer, had less fatty livers, and their glucose metabolism improved.

"This was very surprising, as these two synthases produce exactly the same ceramide product but have completely different effects on the metabolism of the mice," says Hammerschmidt.

On further examination, the researchers found that the key came down to where in the cell the proteins were active. Ceramide synthase 6 regulates those fat molecules inside the mitochondria, and it seems that accumulation of fats there is partly responsible for many of the health problems.

The team says that this research could eventually lead to new therapies for diabetes in humans, but as with any mouse study, there's no guarantee that the results will translate.

The research was published in the journal Cell.

Source: Max Planck Society

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