Not too much, not too little

How do cells keep the balance of fats in their membranes just right?
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The expression pattern of FLD-1 in a nematode worm. Image credit: Ruiz et al. (CC BY 4.0)

The saying “you are what you eat” is probably closest to the truth when talking about fats. This is because the outer edge of our cells, known as the cell membrane, is built mostly from the fats found in our diet. Yet, there is a possible problem with this situation. Based on their chemical make-up, fats can be classed as saturated or unsaturated. Saturated fats, like those in butter, pack closely together and tend to be solid at room temperature. Unsaturated fats, like oils from vegetables and fish, pack together more loosely, making them runny. This means that eating too much saturated fat can cause our cell membranes to become unhealthily rigid, while too much unsaturated fat may make them too fluid.

To avoid these problems, cells can manage the fat content of their membranes, even as the diet fluctuates. Certain proteins alert cells when the membrane is too rigid, and the cells respond by converting saturated fats in the membrane into unsaturated fats. Previous research has found a few of these proteins in humans and nematode worms, but it was not clear what would happen if these sensors were not present or not working as they should. Could other proteins monitor the membrane too?

To answer this question, Ruiz, Bodhicharla, Svensk et al. took nematode worms that could not make the known sensor proteins and used genetic methods that stop them producing various other proteins too. The mutant worms were then fed a diet rich in saturated fats, and the effect on the fats in the cell membrane was measured. From these experiments, new proteins were found that regulate the composition of fats in cell membranes. In the worms, it turns out that a protein called FLD-1 normally limits the amount of unsaturated fats in the membrane. Stopping the worms from producing this protein made the membrane less rigid. The same applied in human cells with proteins called TLCD1 and TLCD2. More unsaturated fats were incorporated when these two proteins were removed, restoring the membranes to a healthy state despite the cells being grown in the presence of excess saturated fat. Together, these findings suggest that targeting these proteins could potentially lead to new treatments for diseases like diabetes, where cell membranes are too rigid.