Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport

Membranes made of molecules called lipids surround every living cell and also form compartments inside the cell. There are hundreds of different lipid molecules that can be found in membranes. The amount of each type within the membrane can vary, which affects the flexibility and other physical properties of the membrane. One type of lipid found in membranes is called arachidonic acid. It is involved in cell communication and other processes, and is required for young animals to grow and develop properly. An enzyme called LPCAT3 is thought to incorporate arachidonic acid into membranes, but this has not yet been proven to occur in living animals. Here, Hashidate-Yoshida, Harayama et al. studied the role of LPCAT3 in newborn mice. The experiments show that this enzyme is found at high levels in the intestine and liver. Mice that lacked LPCAT3 had much lower levels of arachidonic acid compared with normal mice. These mice also showed signs of severe intestinal damage due to the build up of lipids from their mother's milk, and died within a few days of being born. The mice that lacked LPCAT3 had different amounts of another type of lipid—called triacylglycerols—in their intestine and liver. Normally, these lipids would be assembled into larger molecules called lipoproteins that are released into the blood stream and used in the muscles and other parts of the body. However, Hashidate-Yoshida, Harayama et al. found that in the mice missing LPCAT3, the triacylglycerols did not get assembled into lipoproteins and so they accumulated inside the intestine and liver cells. The experiments also show that high levels of arachidonic acid and other similar lipids in the membrane enable triacylglycerol molecules to cluster together, which increases the production of lipoproteins. Hashidate-Yoshida, Harayama et al.'s findings suggest that LPCAT3 incorporates arachidonic acid into the membrane of intestine and liver cells, which enables triacylglycerols to be assembled into lipoproteins. The next challenge will be to find out if LPCAT3 is also important for the production of lipoproteins in humans. If it is, then developing new therapies that alter the activity of this enzyme might be beneficial for patients with abnormal levels of lipids in the blood (known as dyslipidemia).