+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Polyunsaturated fatty acid supplementation reverses cystic fibrosis-related fatty acid abnormalities in CFTR-/- mice by suppressing fatty acid desaturases



Polyunsaturated fatty acid supplementation reverses cystic fibrosis-related fatty acid abnormalities in CFTR-/- mice by suppressing fatty acid desaturases



Journal of Nutritional Biochemistry 26(1): 36-43



Cystic fibrosis patients and model systems exhibit consistent abnormalities in metabolism of polyunsaturated fatty acids that appear to play a role in disease pathophysiology. Recent in vitro studies have suggested that these changes are due to overexpression of fatty acid desaturases that can be reversed by supplementation with the long-chain polyunsaturated fatty acids docosahexaenoate and eicosapentaenoate. However, these findings have not been tested in vivo. The current study aimed to test these results in an in vivo model system, the CFTR(-/-) knockout mouse. When compared with wild-type mice, the knockout mice exhibited fatty acid abnormalities similar to those seen in cystic fibrosis patients and other model systems. The abnormalities were confined to lung, ileum and pancreas, tissues that are affected by the disease. Similar to in vitro models, these fatty acid changes correlated with increased expression of Δ5- and Δ6-desaturases and elongase 5. Dietary supplementation with high-dose free docosahexaenoate or a combination of lower-dose docosahexaenoate and eicosapentaenoate in triglyceride form corrected the fatty acid abnormalities and reduced expression of the desaturase and elongase genes in the ileum and liver of knockout mice. Only the high-dose docosahexaenoate reduced histologic evidence of disease, reducing mucus accumulation in ileal sections. These results provide in vivo support for the hypothesis that fatty acid abnormalities in cystic fibrosis result from abnormal expression and activity of metabolic enzymes in affected cell types. They further demonstrate that these changes can be reversed by dietary n-3 fatty acid supplementation, highlighting the potential therapeutic benefit for cystic fibrosis patients.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058572939

Download citation: RISBibTeXText

PMID: 25448610

DOI: 10.1016/j.jnutbio.2014.09.001


Related references

A specific combined long-chain polyunsaturated fatty acid supplementation reverses fatty acid profile alterations in a mouse model of chronic asthma. Lipids in Health and Disease 18(1): 16, 2019

Polyethen oid fatty acid metabolism. 2. Deposition of polyunsaturated fatty acids in fat-deficient rats upon single fatty acid supplementation. Arch. Biochem 25: 1-12, 1950

T1019 A Randomized, Masked, Controlled Study of Omega-3 Polyunsaturated Fatty Acid vs Monounsaturated Fatty Acid Diet Supplementation for the Treatment of Nonalcoholic Fatty Liver Disease. Gastroenterology 136(5): A-847-A-848, 2009

Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances. Nutrients 8(1):, 2016

Significance of fatty acid supplementation on profiles of cell growth, fatty acid, and gene expression of three desaturases in Mucor rouxii. Applied Microbiology and Biotechnology 80(3): 499-506, 2008

Decreased Fatty Acid β-Oxidation Is the Main Cause of Fatty Liver Induced by Polyunsaturated Fatty Acid Deficiency in Mice. Tohoku Journal of Experimental Medicine 242(3): 229-239, 2017

Fatty acid alterations and n-3 fatty acid supplementation in cystic fibrosis. Prostaglandins Leukotrienes and Essential Fatty Acids 77(5-6): 309-318, 2007

Hypothesis: vitamin E complements polyunsaturated fatty acids in essential fatty acid deficiency in cystic fibrosis. Journal of the American College of Nutrition 22(4): 253-257, 2003

Specific phospholipid fatty acid composition of brain regions in mice. Effects of n-3 polyunsaturated fatty acid deficiency and phospholipid supplementation. Journal of Lipid Research 41(3): 465-472, 2000

Transgenic expression of delta-6 and delta-15 fatty acid desaturases enhances omega-3 polyunsaturated fatty acid accumulation in Synechocystis sp. PCC6803. Biotechnology for Biofuels 7(1): 32, 2014

Dietary fatty acid intakes and polyunsaturated fatty acid to saturated fatty acid ratios in a population sample of women with different coronary risks. Clinical Science 78(4): 25P-26P, 1990

Differential effects of saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid on chylomicron metabolism in the small intestine. Atherosclerosis Suppl.s 9(2): 85-86, 2008

Joint effects of fatty acid desaturase 1 polymorphisms and dietary polyunsaturated fatty acid intake on circulating fatty acid proportions. American Journal of Clinical Nutrition 107(5): 826-833, 2018

Fatty aldehyde dehydrogenase is up-regulated by polyunsaturated fatty acid via peroxisome proliferator-activated receptor alpha and suppresses polyunsaturated fatty acid-induced endoplasmic reticulum stress. Febs Journal 276(23): 6956-6970, 2009

Modeled replacement of traditional soybean and canola oil with high-oleic varieties increases monounsaturated fatty acid and reduces both saturated fatty acid and polyunsaturated fatty acid intake in the US adult population. American Journal of Clinical Nutrition 108(3): 594-602, 2018