Metabolism and functions of highly unsaturated fatty acids: An update

This review briefly examines the recent progress in knowledge about the syn thesis and degradation of highly unsaturated fatty acids (HUFA) and their f unctions. Following the cloning of mammalian Delta6-desaturase (D6D), the D 6D mRNA was found in many tissues, including adult brain, maternal organs, and fetal tissue, suggesting an active synthesis of HUFA in these tissues. The cloning also confirmed the long-postulated hypothesis that the same pat hway is followed in n-6 and n-3 HUFA synthesis. Dietary n-6 and n-3 HUFA bo th induce fatty acid oxidation enzymes in peroxisomes when compared to thei r respective precursor polyunsaturated fatty acids. This suggests that pero xisomes may be the primary site of HUFA degradation when HUFA are supplied in excess from the diet. Peroxisome proliferators strongly induce the enzym es for the HUFA synthesis. The mechanism of this induction is currently unk nown. Recent studies revealed new HUFA functions that are not mediated by e icosanoids. These functions include endocytosis/exocytosis, ion-channel mod ulation, DNA polymerase inhibition, and regulation of gene expression. Thes e new discoveries will enable us to reexamine the underlying mechanisms for the classical symptoms of essential fatty acid deficiency as well as vitam in E deficiency. Progress has also been made in understanding the mechanism by which dietary HUFA reduce body fat deposition. One mechanism is inducti on of genes for fatty acid oxidation, which is mediated by peroxisome proli ferator-activated receptor-alpha. Another likely mechanism is that HUFA sup press genes for fatty acid synthesis by reducing both mRNA and protein matu ration of sterol regulatory element binding protein-1.