DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity
Patients and models of cystic fibrosis (CF) exhibit consistent abnormalities of polyunsaturated fatty acid composition, including decreased linoleate (LA) and docosahexaenoate (DHA) and variably increased arachidonate (AA), related in part to increased expression and activity of fatty acid desaturas...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520407837 |
| _version_ | 1818930795543265280 |
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| author | Sarah W. Njoroge Michael Laposata Waddah Katrangi Adam C. Seegmiller |
| author_facet | Sarah W. Njoroge Michael Laposata Waddah Katrangi Adam C. Seegmiller |
| author_sort | Sarah W. Njoroge |
| collection | DOAJ |
| description | Patients and models of cystic fibrosis (CF) exhibit consistent abnormalities of polyunsaturated fatty acid composition, including decreased linoleate (LA) and docosahexaenoate (DHA) and variably increased arachidonate (AA), related in part to increased expression and activity of fatty acid desaturases. These abnormalities and the consequent CF-related pathologic manifestations can be reversed in CF mouse models by dietary supplementation with DHA. However, the mechanism is unknown. This study investigates this mechanism by measuring the effect of exogenous DHA and eicosapentaenoate (EPA) supplementation on fatty acid composition and metabolism, as well as on metabolic enzyme expression, in a cell culture model of CF. We found that both DHA and EPA suppress the expression and activity of Δ5- and Δ6-desaturases, leading to decreased flux through the n-3 and n-6 PUFA metabolic pathways and decreased production of AA. The findings also uncover other metabolic abnormalities, including increased fatty acid uptake and markedly increased retroconversion of DHA to EPA, in CF cells. These results indicate that the fatty acid abnormalities of CF are related to intrinsic alterations of PUFA metabolism and that they may be reversed by supplementation with DHA and EPA. |
| first_indexed | 2024-12-20T04:06:23Z |
| format | Article |
| id | doaj.art-eeaf711532da4cea837a8a2948269d9d |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T04:06:23Z |
| publishDate | 2012-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-eeaf711532da4cea837a8a2948269d9d2022-12-21T19:54:01ZengElsevierJournal of Lipid Research0022-22752012-02-01532257265DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activitySarah W. Njoroge0Michael Laposata1Waddah Katrangi2Adam C. Seegmiller3Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TNDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TNDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TNTo whom correspondence should be addressed; To whom correspondence should be addressed; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TNPatients and models of cystic fibrosis (CF) exhibit consistent abnormalities of polyunsaturated fatty acid composition, including decreased linoleate (LA) and docosahexaenoate (DHA) and variably increased arachidonate (AA), related in part to increased expression and activity of fatty acid desaturases. These abnormalities and the consequent CF-related pathologic manifestations can be reversed in CF mouse models by dietary supplementation with DHA. However, the mechanism is unknown. This study investigates this mechanism by measuring the effect of exogenous DHA and eicosapentaenoate (EPA) supplementation on fatty acid composition and metabolism, as well as on metabolic enzyme expression, in a cell culture model of CF. We found that both DHA and EPA suppress the expression and activity of Δ5- and Δ6-desaturases, leading to decreased flux through the n-3 and n-6 PUFA metabolic pathways and decreased production of AA. The findings also uncover other metabolic abnormalities, including increased fatty acid uptake and markedly increased retroconversion of DHA to EPA, in CF cells. These results indicate that the fatty acid abnormalities of CF are related to intrinsic alterations of PUFA metabolism and that they may be reversed by supplementation with DHA and EPA.http://www.sciencedirect.com/science/article/pii/S0022227520407837fatty acid metabolismgene expressionomega-3 fatty acidsdocosapentaenoateeicosapentaenoate |
| spellingShingle | Sarah W. Njoroge Michael Laposata Waddah Katrangi Adam C. Seegmiller DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity Journal of Lipid Research fatty acid metabolism gene expression omega-3 fatty acids docosapentaenoate eicosapentaenoate |
| title | DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity |
| title_full | DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity |
| title_fullStr | DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity |
| title_full_unstemmed | DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity |
| title_short | DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity |
| title_sort | dha and epa reverse cystic fibrosis related fa abnormalities by suppressing fa desaturase expression and activity |
| topic | fatty acid metabolism gene expression omega-3 fatty acids docosapentaenoate eicosapentaenoate |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520407837 |
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