Fatty Acid Transport Proteins

Fatty acid transport proteins (FATPs) are a group of proteins that play a critical role in moving fatty acids throughout the body. Some FATPs deliver fatty acids to cells of organs such as muscle or heart, while other FATPs move fatty acids around within the cell to specific organelles such as the mitochondria or the nucleus. Once inside the cell, fatty acids may be used for many cellular activities including making energy or affecting gene expression. Traditionally, it was believed that fatty acids entered a cell by diffusion (without any help). However, over the course of the last decade, FATPs were discovered and their critical role is beginning to be fully understood. They are often considered to be a rate-limiting step in fatty acid metabolism. Only the liver and fat tissue can synthesize fatty acids, a process known as de novo synthesis, and thus all other organs, such as the heart, kidneys and muscle depend on fatty acids to be delivered which highlight the critical role that FATPs play in metabolism.

There are many different types of FATPs. Some of these include fatty acid translocase (FAT/CD36), FATP, fatty acid binding protein-plasma membrane (FATPpm), fatty acid-binding protein-cellular (FATPc), and Acyl CoA synthase. FAT/CD36 is located within the cell membrane and plays a critical role in transporting fatty acids inside a cell. It is necessary for normal fat and sugar metabolism in the body. There have been six FATPs discovered to date in humans that are known as FATP1–FATP6, respectively. They also are responsible for bring fatty acids inside a cell. It is believed that they change the structure of the fatty acid, which allows it to pass through the cell membrane easier. FATPpm helps facilitate the movement of fatty acids through the cell membrane, while FATPc helps move fatty acids within the cell to their target (i.e., the nucleus or mitochondria). Acyl-CoA synthase is an enzyme that was primarily believed to play a role in making fatty acids. Recent studies have found that it may also have a role in transporting fatty acids within the cell.

There are some known medical conditions that may be related to abnormal FATPs. Some studies that have removed FATPs in mice have been used to identify several metabolic defects. Mice that do not have any FAT/CD36 cannot perform fat oxidation and tire out very quickly during exercise. Conversely, mice that have extra FAT/CD36 levels (through genetic alterations) can sustain exercise for longer time than mice that have normal FAT/CD36 levels. Mice that lack FAT/CD36 are also less likely to become obese while consuming a high-fat diet. In humans, FAT/CD36 deficiencies exist at high levels in some populations. Three to 10 percent of Asians and 5 to 18.5 percent of African Americans have a deficiency of FAT/CD36, while only 0.3 percent of Caucasians are [Page 268]deficient. The lack of FAT/CD36 is associated with abnormal fat metabolism in these patients and increase risk for heart disease (including enlarged heart), insulin resistance, and Type 2 diabetes mellitus.