Wetenschap - 1 december 2010

Protein protects against deadly fat

A special protein appears to protect us against the damaging effects of saturated fat. Wageningen research has revealed how this works for the first time.

Angpt14 is the unpronounceable name of the protein that protects most of us from considerable harm. It was known that this substance inhibits fat absorption, but the role of Angpt14 turns out to be bigger than that. Without this protein, in fact, saturated fat gives off a deadly toxin. This was discovered by Sander Kersten and fellow researchers at the department of Human Nutrition. In their research they gave mice that did not make this protein food rich in saturated fat. 'Over the course of several weeks, the animals developed serious infections and eventually died', says the researcher. Kersten and colleagues published their findings in the prominent journal Cell Metabolism at the end of November.
They took their research further than this, though. Noting the serious consequences of the absence of Angptl14, the researchers wanted to know what this would mean at cell and molecular level. Their detective work brought to light a distinction between the effect of 'common' saturated fats and a smaller group known as medium chain saturated fats.

Enormous fat concentrations
Whereas the mice that were given common saturated fats became very ill, the mice that ate medium chain saturated fats stayed healthy. The difference between the two types of fat lies mainly in the absorption route, says Kersten: 'The classic saturated fats are wrapped up in a sort of protein coating in the intestines and enter the blood through the lymphatic system. The medium chain fats are not wrapped up like that and enter the blood directly.' The researchers guessed then that the lymphatic system played a key role in the infections.
Microscopic research on the infected lymph glands revealed a surprising picture. Kersten points to a microscopic photo of an infected lymph gland: 'We couldn't place these enormous cells at first. Look, you can see that they are filled with something; that is fat.' The team discovered that the large cells were fused macrophages. Macrophages are white blood cells that specialize in mopping up things like bacteria. In this case they were melted together by the massive concentration of fat passing through the lymph glands and they ate unlimited fat, which caused an infection. 'The infected lymph gland is full of these 'foam cells', and this was the start of an inflammatory response that eventually went right out of control', says Kersten. 'The role of the Angpt14 protein is much clearer now: it prevents the macrophages from gorging themselves on fat and thereby inhibits the inflammatory response.'

Very important
Although unsaturated fats also get transported into the blood via the lymphatic system, surprisingly, they do not cause an inflammatory response. Kersten thinks this has to do with the stimulating effect of these fats on the formation of the protective Angpt14 protein. Also, the intake of unsaturated fats by macrophages does not set off an inflammatory response.
Kersten believes his research is of great significance to humans, because humans have the Angpt14 protein too, and it protects them against saturated fats just as it does mice. In about three percent of the population, however, the protein exhibits only half the normal activity levels, and in one in ten thousand people it is entirely absent. 'A diet low in saturated fats would be suitable for them.'

Hans Wolkers