Metabolism of very long chain fatty acids and pathophysiological role of fatty acid elongase -1 (ELOVL1)

<p>Many human pathologies are closely associated with lipid disorders. Very long chain fatty acids (VLCFA) are responsible for stiffening cell membranes and act as neural signalling molecules. Their deficiency may cause cell disintegration, neurodegenerative diseases, muscle atrophy, and optic atrophy. In 2017, our research team discovered a new genetic disorder in paediatric patients caused by the p.Ser165Phe mutation in the gene encoding fatty acid elongase 1 (ELOVL1), called IKSHD (ichthyosis keratoderma, spasticity, mild hypomyelination, and dysmorphic features). This mutation results in a reduction of VLCFA, including C24:0–C28:0 and C26:1, as well as the accumulation of shorter VLCFA, such as C20:0 and C22:0, which may result from altered substrate specificity of the mutated enzyme. The ELOVL1 mutation leads to hypomyelination of the nervous system and progressive disturbances of its function, as well as skin diseases due to abnormalities in sphingolipids, of which VLCFA are significant components. The data above suggest a vital role for VLCFA and ELOVL1 in human pathophysiology. Therefore, this project aims to discover the pathophysiological significance of alterations in VLCFA levels and ELOVL1 gene expression. For this purpose, a knock-in mouse model with the ELOVL1 p.Ser165Phe mutation was generated.</p>