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Nutrition and Disease

Increased Tissue Arachidonic Acid and Reduced Linoleic Acid in a Mouse Model of Cystic Fibrosis Are Reversed by Supplemental Glycerophospholipids Enriched in Docosahexaenoic Acid^1,2,3

⁴ INSERM, U 476 Nutrition Humaine et Lipides, Marseille, F-13385, France ⁵ INRA, UMR1260 Nutriments Lipidiques et Prévention des Maladies Métaboliques, Marseille, F-13385, France ⁶ Université de la Méditerranée Aix-Marseille 2, Faculté de Médecine, Marseille, F-13385 France ⁷ Clinical Chemistry, Université Catholique de Louvain, B-1200 Brussels, Belgium ⁸ Cell Physiology, Université Catholique de Louvain, B-1200 Brussels, Belgium ⁹ Paediatric Pulmonology, Université Catholique de Louvain, B-1200 Brussels, Belgium

An imbalance in (n-6)/(n-3) PUFA has been reported in cystic fibrosis (CF) patients. Glycerophospholipids enriched in docosahexaenoic acid (GPL-DHA) have been shown to regulate the (n-6)/(n-3) fatty acid ratio in the elderly. Here, we tested the effect of GPL-DHA supplementation on PUFA status in F508del homozygous CF mice. GPL-DHA liposomes were administrated by gavage (60 mg DHA/kg daily, i.e. at maximum 1.4 mg DHA/d) to 1.5-mo-old CF mice (CF+DHA) and their corresponding wild-type (WT) homozygous littermates (WT+DHA) for 6 wk. The PUFA status of different tissues was determined by GC and compared with control groups (CF and WT). There was an alteration in the (n-6) PUFA pathway in several CF-target organs in CF compared with WT mice, as evidenced by a higher level of arachidonic acid (AA) in membrane phospholipids or whole tissue (21 and 39% in duodenum-jejunum, 32 and 38% in ileum, and 19 and 43% in pancreas). Elevated AA levels were associated with lower linoleic acid (LA) and higher dihomo--linolenic acid levels. No DHA deficiency was observed. GPL-DHA treatment resulted in different PUFA composition changes depending on the tissue (increase in LA, decrease in elevated AA, DHA increase, increase in (n-6)/(n-3) fatty acid ratio). However, the DHA/AA ratio consistently increased in all tissues in CF+DHA and WT+DHA mice. Our study demonstrates the effectiveness of an original oral DHA formulation in counter-balancing the abnormal (n-6) fatty acid metabolism in organs of CF mice when administrated at a low dose and highlights the potential of the use of GPL-DHA as nutritherapy for CF patients.

^* To whom correspondence should be addressed. E-mail: thierry.coste{at}univmed.fr.

Manuscript received 3 June 2009. Initial review completed 30 June 2009. Revision accepted 2 October 2009.