How Is Fat Bad For You?

Dov Michaeli

First posted 7/22/11 on The Doctor Weighs In

Since today is Friday, and we are already in a semi relaxed weekend mode, we’ll keep it short.

Yesterday’s column dealt with a saturated fat, choline (and its precursor lecithin), and demonstrated on the molecular level how it causes the formation of atherosclerotic plaque. What was missing from that neat picture was one component that we know is important in diabetes and atherosclerosis: inflammation. In the last few years scientists have become more and more convinced that the fundamental process of these diseases is inflammatory. But how exactly do saturated fats cause inflammation?

In an April 14, 2011 paper in Nature, Jenny Ting and her team at the University of North Carolina at Chapel Hill described an important part of the story. Macrophages are cells of the immune system. They contain a complex of inflammatory proteins that are called the inflammasome. They did something quite simple: they exposed the macrophages to palmitate, a saturated fatty acid that is commonly present in animal fats. Palmitate stimulated the inflammasome, causing the macrophages to release a powerful inflammatory protein called IL-1β (interleukin-1β). This protein blocked insulin signaling in cultured liver cells. They went further and fed mice for 12 weeks with a high fat diet. Result: the mice developed insulin resistance in the liver, fat and muscle tissue. This is the hallmark of diabetes type 2.

Like any careful scientist, we should ask 2 critical questions: what’s the proof that it was the saturated fatty acid that triggered the inflammasome, and not any old fatty acid? They answered this question by exposing the macrophages to unsaturated fatty acids, which are present in fat of plant origin. No activation of the inflammasome occurred. The other question we should ask: how do we know that the inflammasome was the culprit, and not just an innocent bystander?  They created macrophages that lacked the genes for the inflammasome, and those cells failed to release IL-1β.

Q.E.D.

This study is a wonderful example of how careful science is done. But it goes beyond “inside baseball”: it actually has some potentially important practical consequences. It opens up two possible points of attack on inflammation, diabetes type2 and heart disease. I am sure that the laboratories of drug companies are already hard at work screening drugs that can inhibit activation of the inflammasome, and release of IL-1β.

Until now we saw correlations between high-fat diet and insulin resistance, diabetes and heart disease. But correlation is not causation. This work uncovered the molecular secret of how saturated fats cause the cascade that ends up in inflammation and its daughters, diabetes and heart disease.

Bravo to the investigators. And you, dear reader, eat your peas and stay away from bacon –it’s not Kosher, in more ways than one.

Dov Michaeli MD PhD is a basic researcher who blogs on The Doctor Weighs In.