Fatty Acid Desaturase 3 (Fads3) is a singular member of the Fads cluster

Abstract

Since its identification in 2000, no function has been attributed to the Fatty Acid Desaturase 3 (Fads3) gene. This gene is located within the Fads cluster, which also contains Fads1 and Fads2, coding respectively for the Δ5- and Δ6- desaturases. Based on the sequence homology between these three genes, Fads3 may be a new fatty acid desaturase. It is thus essential to understand its involvement in Polyunsaturated Fatty Acid (PUFA) biosynthesis in order to improve our knowledge on lipid metabolism. Gene expression studies provided evidences on the specificity of Fads3 compared to Fads1 and Fads2, concerning the tissue distribution, alternative splicing and regulation. These works also identified possible physiological functions in which Fads3 could be involved. Thus, the Fads3 gene was transcripted in many tissues, and displayed a weak expression in the liver compared to other organs such as the lung or spleen. Fads3 was also showed to be a target gene for NK-κB, MYCN or p63 transcription factors and could consequently be involved in cell survival mechanisms. Polymorphism analysis underlined the possible implication of Fads3 in lipid homeostasis, particularly by modulating cholesterol and triglyceride plasma levels. In terms of proteins, FADS3 has been recently described in rodents. One of the identified isoforms may display the classical structure of a fatty acid desaturase but no enzymatic activity has been observed yet. Therefore, it is essential to consider the desaturase diversity in terms of catalysis and substrates to elucidate the FADS3 function.