Long-term Dietary (n-3) Polyunsaturated Fatty Acids Show Benefits to the Lungs of Cftr F508del Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Jun 2

PMID 29856782

Citations 6

Authors

Celine Portal

Valerie Gouyer

Renaud Leonard

Marie-Odile Husson

Frederic Gottrand

Jean-Luc Desseyn

Affiliations

Soon will be listed here.

Abstract

Introduction: The pro-inflammatory status of cystic fibrosis (CF) patients promotes pulmonary colonization with opportunist and pathogenic bacteria, which is favored by a sticky mucus. Oral supplementation with (n-3) long chain polyunsaturated fatty acids (LC-PUFA) has shown anti-inflammatory effects. The aim of this study was to demonstrate the positive effects of a long-term diet enriched in (n-3) LC-PUFA on the lungs of Cftr F508del mice.

Materials And Methods: Breeding CftrΔF508del/+ mice received a control diet or a diet enriched in (n-3) LC-PUFA for 5 weeks before mating, gestation and lactation. After weaning, the offspring were given the same diet as their mother until post-natal day 60. The effects of (n-3) LC-PUFA supplementation on the lungs were evaluated in homozygous Cftr F508del mice and their wild-type littermates after acute lung inflammation induced by Pseudomonas aeruginosa lipopolysaccharide (LPS) inhalation.

Results: (n-3) LC-PUFA enrichment of mothers contributes to enrichment of mammary milk and cell membrane of suckling pups. Cftr F508del mice exhibited growth retardation and lung damage with collapsed alveoli, hyperplasia of bronchial epithelial cells and inflammatory cell infiltration. The (n-3) LC-PUFA diet corrected the growth delay of Cftr F508del mice and decreased hyperplasia of bronchial epithelial cells. Besides decreasing metaplasia of Club cells after LPS inhalation, (n-3) LC-PUFA modulated lung inflammation and restricted lung damage.

Conclusion: Long-term (n-3) LC-PUFA supplementation shows moderate benefits to the lungs of Cftr F508del mice.

Citing Articles

Can Bioactive Food Substances Contribute to Cystic Fibrosis-Related Cardiovascular Disease Prevention?.

Trandafir L, Frasinariu O, Tarca E, Butnariu L, Leon Constantin M, Moscalu M Nutrients. 2023; 15(2).

PMID: 36678185 PMC: 9860597. DOI: 10.3390/nu15020314.

Virtual Drug Repositioning as a Tool to Identify Natural Small Molecules That Synergize with Lumacaftor in F508del-CFTR Binding and Rescuing.

Fossa P, Uggeri M, Orro A, Urbinati C, Rondina A, Milanesi M Int J Mol Sci. 2022; 23(20).

PMID: 36293130 PMC: 9602983. DOI: 10.3390/ijms232012274.

Impact of Altered Gut Microbiota and Its Metabolites in Cystic Fibrosis.

Thavamani A, Salem I, Sferra T, Sankararaman S Metabolites. 2021; 11(2).

PMID: 33671639 PMC: 7926988. DOI: 10.3390/metabo11020123.

CFTR Correctors and Antioxidants Partially Normalize Lipid Imbalance but not Abnormal Basal Inflammatory Cytokine Profile in CF Bronchial Epithelial Cells.

Veltman M, De Sanctis J, Stolarczyk M, Klymiuk N, Bahr A, Brouwer R Front Physiol. 2021; 12:619442.

PMID: 33613309 PMC: 7891400. DOI: 10.3389/fphys.2021.619442.

The Microbiome in Cystic Fibrosis Pulmonary Disease.

Francoise A, Hery-Arnaud G Genes (Basel). 2020; 11(5).

PMID: 32403302 PMC: 7288443. DOI: 10.3390/genes11050536.

References

Bruscia E, Zhang P, Barone C, Scholte B, Homer R, Krause D . Increased susceptibility of Cftr-/- mice to LPS-induced lung remodeling. Am J Physiol Lung Cell Mol Physiol. 2016; 310(8):L711-9. PMC: 4836110. DOI: 10.1152/ajplung.00284.2015. View

Zeiher B, Eichwald E, Zabner J, Smith J, Puga A, McCray Jr P . A mouse model for the delta F508 allele of cystic fibrosis. J Clin Invest. 1995; 96(4):2051-64. PMC: 185844. DOI: 10.1172/JCI118253. View

Bergamini G, Cigana C, Sorio C, Della Peruta M, Pompella A, Corti A . Effects of azithromycin on glutathione S-transferases in cystic fibrosis airway cells. Am J Respir Cell Mol Biol. 2008; 41(2):199-206. DOI: 10.1165/rcmb.2008-0013OC. View

Mimoun M, Coste T, Lebacq J, Lebecque P, Wallemacq P, Leal T . Increased tissue arachidonic acid and reduced linoleic acid in a mouse model of cystic fibrosis are reversed by supplemental glycerophospholipids enriched in docosahexaenoic acid. J Nutr. 2009; 139(12):2358-64. DOI: 10.3945/jn.109.110999. View

Tiesset H, Bernard H, Bartke N, Beermann C, Flachaire E, Desseyn J . (n-3) long-chain PUFA differentially affect resistance to Pseudomonas aeruginosa infection of male and female cftr-/- mice. J Nutr. 2011; 141(6):1101-7. DOI: 10.3945/jn.110.134585. View

Freedman S, Katz M, Parker E, Laposata M, Urman M, Alvarez J . A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr(-/-) mice. Proc Natl Acad Sci U S A. 1999; 96(24):13995-4000. PMC: 24179. DOI: 10.1073/pnas.96.24.13995. View

Byard P . Early childhood growth in patients with cystic fibrosis. Ann Hum Biol. 1990; 17(6):483-99. DOI: 10.1080/03014469000001262. View

Legssyer R, Huaux F, Lebacq J, Delos M, Marbaix E, Lebecque P . Azithromycin reduces spontaneous and induced inflammation in DeltaF508 cystic fibrosis mice. Respir Res. 2006; 7:134. PMC: 1637104. DOI: 10.1186/1465-9921-7-134. View

Viera A, Garrett J . Understanding interobserver agreement: the kappa statistic. Fam Med. 2005; 37(5):360-3. View

10.

Tetaert D, Pierre M, Demeyer D, Husson M, Beghin L, Galabert C . Dietary n-3 fatty acids have suppressive effects on mucin upregulation in mice infected with Pseudomonas aeruginosa. Respir Res. 2007; 8:39. PMC: 1899493. DOI: 10.1186/1465-9921-8-39. View

11.

Wu H, Yang J, Su E, Li L, Zhao C, Yang X . Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice. PLoS One. 2014; 9(3):e93003. PMC: 3966846. DOI: 10.1371/journal.pone.0093003. View

12.

Freedman S, Blanco P, Zaman M, Shea J, Ollero M, Hopper I . Association of cystic fibrosis with abnormalities in fatty acid metabolism. N Engl J Med. 2004; 350(6):560-9. DOI: 10.1056/NEJMoa021218. View

13.

Husson M, Ley D, Portal C, Gottrand M, Hueso T, Desseyn J . Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids. J Infect. 2016; 73(6):523-535. DOI: 10.1016/j.jinf.2016.10.001. View

14.

Freedman S, Weinstein D, Blanco P, Martinez-Clark P, Urman S, Zaman M . Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid. J Appl Physiol (1985). 2002; 92(5):2169-76. DOI: 10.1152/japplphysiol.00927.2001. View

15.

Sinaasappel M, Stern M, Littlewood J, Wolfe S, Steinkamp G, Heijerman H . Nutrition in patients with cystic fibrosis: a European Consensus. J Cyst Fibros. 2004; 1(2):51-75. DOI: 10.1016/s1569-1993(02)00032-2. View

16.

Meyer M, Huaux F, Gavilanes X, van den Brule S, Lebecque P, Lo Re S . Azithromycin reduces exaggerated cytokine production by M1 alveolar macrophages in cystic fibrosis. Am J Respir Cell Mol Biol. 2009; 41(5):590-602. DOI: 10.1165/rcmb.2008-0155OC. View

17.

Bilsborough J, Chadwick E, Mudri S, Ye X, Henderson Jr W, Waggie K . TACI-Ig prevents the development of airway hyperresponsiveness in a murine model of asthma. Clin Exp Allergy. 2008; 38(12):1959-68. DOI: 10.1111/j.1365-2222.2008.03099.x. View

18.

Dhooghe B, Noel S, Huaux F, Leal T . Lung inflammation in cystic fibrosis: pathogenesis and novel therapies. Clin Biochem. 2014; 47(7-8):539-46. DOI: 10.1016/j.clinbiochem.2013.12.020. View

19.

Hecker M, Behnk A, Morty R, Sommer N, Vadasz I, Herold S . PPAR-α activation reduced LPS-induced inflammation in alveolar epithelial cells. Exp Lung Res. 2015; 41(7):393-403. DOI: 10.3109/01902148.2015.1046200. View

20.

Tirkos S, Newbigging S, Nguyen V, Keet M, Ackerley C, Kent G . Expression of S100A8 correlates with inflammatory lung disease in congenic mice deficient of the cystic fibrosis transmembrane conductance regulator. Respir Res. 2006; 7:51. PMC: 1456967. DOI: 10.1186/1465-9921-7-51. View