Essential fatty acid deficiency in well nourished young cystic fibrosis patients

Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF. CF (antisense) cells demonstrated decreased levels of LA and DHA compared with wild type (WT, sense) cells expressing normal CFTR. Cellular uptake of LA and DHA was higher in CF cells compared with WT cells at 1 h and 4 h. Subsequent incorporation of LA and DHA into most lipid classes and individual phospholipids was also increased in CF cells. The metabolic conversion of LA to n-6 metabolites, including 18:3n-6 and arachidonic acid, was upregulated in CF cells, indicating increased flux through the n-6 pathway. Supplementing CF cells with DHA inhibited the production of LA metabolites and corrected the n-6 fatty acid defect. In conclusion, the evidence suggests that low LA level in cultured CF cells is due to its increased metabolism, and this increased LA metabolism is corrected by DHA supplementa-

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confidence: 64%

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confidence: 71%

A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA

Al-Turkmani

Andersson

Alturkmani

et al. 2008

“…These alterations include a decrease in circulating essential fatty acids ( 19,20 ), phospholipids, and lysophospholipids ( 21 ); decreased polyunsaturated fatty acids in lung, intestine, and pancreas of mice ( 22,23 ) and nasal cells of patients ( 24 ), mostly associated with an imbalanced n-3/n-6 ratio; and decreased linoleic acid ( 19,25 ) and lipoxin A4 in lung exudates from patients ( 26 ). These alterations have been attributed largely to malabsorption ( 19 ), increased fl ux through the n-6 biosynthetic pathway ( 25,27,28 ), and an alteration in the methionine-homocysteine cycle ( 29,30 ).…”

Section: Lc-msmentioning

confidence: 99%

Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients

Ollero

Astarita

Guerrera

et al. 2011

Cystic fi brosis (CF) is associated with abnormal lipid metabolism. We have recently shown variations in plasma levels of several phosphatidylcholine (PC) and lysophopshatidylcholine (LPC) species related to disease severity in CF patients. Here our goal was to search for blood plasma lipid signatures characteristic of CF patients bearing the same mutation (F508del) and different phenotypes, and to study their correlation with forced expiratory volume in 1 s (FEV1) and Pseudomonas aeruginosa chronic infection, evaluated at the time of testing (t = 0) and three years later (t = 3). Samples from 44 F508del homozygotes were subjected to a lipidomic approach based on LC-ESI-MS. Twelve free fatty acids were positively correlated with FEV1 at t = 0 (n = 29). Four of them (C20:3n-9, C20:5n-3, C22:5n-3, and C22:6n-3) were also positively correlated with FEV1 three years later, along with PC(32:2) and PC(36:4) (n = 31). Oleoylethanolamide (OEA) was negatively correlated with FEV1 progression (n = 17). Chronically infected patients at t = 0 showed lower PC(32:2), PC(38:5), and C18:3n-3 and higher cholesterol, cholesterol esters, and triacylglycerols (TAG). Chronically infected patients at t = 3 showed significantly lower levels of LPC(18:0). These results suggest a potential prognostic value for some lipid signatures in, to our knowledge, the fi rst longitudinal study aimed at identifying lipid biomarkers for CF. -Ollero, M., G. Astarita, I. C. Guerrera, I. Sermet-Gaudelus, S.

“…Current high-fat, hypercaloric nutritional strategies and improved pancreas enzyme replacement therapies can usually maintain patients in optimal nutritional status, thus normalizing EFA status in many CF patients (5). Nonetheless, several reports still indicate the occurrence of EFA deficiency in CF (6)(7)(8). Although some authors have suggested that residual fat malabsorption and increased EFA turnover in CF may compromise EFA status (9,10), the exact pathophysiology of EFA deficiency in CF patients has not been elucidated.…”

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confidence: 99%

No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis

Werner¹,

Bongers²,

Bijvelds

et al. 2004

A deficiency of essential fatty acids (EFA) is frequently described in cystic fibrosis (CF), but whether this is a primary consequence of altered EFA metabolism or a secondary phenomenon is unclear. It was suggested that defective long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes to the CF phenotype. To establish whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects LCPUFA synthesis, we quantified EFA metabolism in cftr ؊ / ؊ CAM and cftr ؉ / ؉ CAM mice. Effects of intestinal phenotype, diet, age, and genetic background on EFA status were evaluated in cftr ؊ / ؊ CAM mice, ⌬ F508/ ⌬ F508 mice, and littermate controls. EFA metabolism was measured by 13 C stable isotope methodology in vivo. EFA status was determined by gas chromatography in tissues of cftr ؊ / ؊ CAM mice, ⌬ F508/ ⌬ F508 mice, littermate controls, and C57Bl/6 wild types fed chow or liquid diet. After enteral administration of [ 13 C]EFA, arachidonic acid (AA) and docosahexaenoic acid (DHA) were equally 13 C-enriched in cftr ؊ / ؊ CAM and cftr ؉ / ؉ CAM mice, indicating similar EFA elongation/desaturation rates. LA, ALA, AA, and DHA concentrations were equal in pancreas, lung, and jejunum of chow-fed cftr ؊ / ؊ CAM and ⌬ F508/ ⌬ F508 mice and controls. LCPUFA levels were also equal in liquid diet-weaned cftr ؊ / ؊ CAM mice and littermate controls, but consistently higher than in age-and diet-matched C57Bl/6 wild types. We conclude that cftr ؊ / ؊ CAM mice adequately absorb and metabolize EFA, indicating that CFTR dysfunction does not impair LCPUFA synthesis. A membrane EFA imbalance is not inextricably linked to the CF genotype. EFA status in murine CF models is strongly determined by genetic background. -Werner, A., M. E. J. Bongers, M. J. Bijvelds, H. R. de Jonge, and H. J. Verkade. No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis.