PEROXISOMAL DYSFUNCTION ASSOCIATED WITH E SSENTIAL FATTY-ACID DEFICIENCY

Peroxisomes are intracellular organelles responsible for several essen tial metabolic functions. Peroxisomal dysfunction may be secondary to defects in the biogenesis and/or assembly of peroxisomes, but it may a lso be secondary to metabolic disorders. Having shown that nearly half of our pediatric Cystic Fibrosis (CF) population had biochemical evid ence of essential fatty acid (EFA) deficiency, we then noted from the phospholipid analysis of red cells an increase in very long chain fatt y acids as as a decrease in plasmalogens, two markers suggestive of a disorder in the integrity of peroxisomes. These results then led us to create an EFA deficient animal model which enabled us to reproduce th ese indices of peroxisomal dysfunction. Finally, beta-carotene supplem entation (15 mg t.i.d.) in twelve CF patients, not only corrected lipi d peroxidation, secondary to an imbalance between pro- and anti-oxydan ts but also peroxisomal function while improving the EFA status. These data raise the hypothesis that lipid peroxidation may be in part resp onsible for EFA deficiency and may lead to peroxisomal dysfunction. Th e understanding of these mechanisms has important clinical implication s since it may lead to new therapeutic strategies.