Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species[S]
Enhanced production of monounsaturated fatty acids (FA) derived from carbohydrate-enriched diets has been implicated in the development of obesity and insulin resistance. The FA elongases Elovl-5 and Elovl-6 are regulated by nutrient and hormone status, and have been shown using intact yeast and mam...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-07-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520371091 |
| _version_ | 1828938058902274048 |
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| author | Christopher D. Green Cansel G. Ozguden-Akkoc Yun Wang Donald B. Jump L. Karl Olson |
| author_facet | Christopher D. Green Cansel G. Ozguden-Akkoc Yun Wang Donald B. Jump L. Karl Olson |
| author_sort | Christopher D. Green |
| collection | DOAJ |
| description | Enhanced production of monounsaturated fatty acids (FA) derived from carbohydrate-enriched diets has been implicated in the development of obesity and insulin resistance. The FA elongases Elovl-5 and Elovl-6 are regulated by nutrient and hormone status, and have been shown using intact yeast and mammalian microsome fractions to be involved in the synthesis of monounsaturated FAs (MUFA). Herein, targeted knockdown and overexpression of Elovl-5 or Elovl-6 was used to determine their roles in de novo synthesis of specific MUFA species in mammalian cells. Treatment of rat insulinoma (INS)-1 cells with elevated glucose increased de novo FA synthesis and the ratio of MUFAs to saturated FAs. Elovl-5 knockdown decreased elongation of 16:1,n-7. Elovl-5 overexpression increased synthesis of 18:1,n-7; however, this increase was dependent on stearoyl-CoA desaturase–driven 16:1,n-7 availability. Knockdown of Elovl-6 decreased elongation of 16:0 and 16:1,n-7, resulting in accumulation of 16:1,n-7. Elovl-6 overexpression preferentially drove synthesis of 16:0 elongation products 18:0 and 18:1,n-9 but not 18:1,n-7. These findings demonstrate that coordinated induction of FA elongase and desaturase activity is required for balanced synthesis of specific n-7 versus n-9 MUFA species. Given the relative abundance of 16:0 to 16:1,n-7 and the specificity of Elovl-6 for 16:0, Elovl-6 is a major elongase for 18:1,n-9 production. |
| first_indexed | 2024-12-14T02:36:37Z |
| format | Article |
| id | doaj.art-b013ed97b06c4d96adf6e3290255e3a4 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T02:36:37Z |
| publishDate | 2010-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-b013ed97b06c4d96adf6e3290255e3a42022-12-21T23:20:07ZengElsevierJournal of Lipid Research0022-22752010-07-0151718711877Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species[S]Christopher D. Green0Cansel G. Ozguden-Akkoc1Yun Wang2Donald B. Jump3L. Karl Olson4Departments of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824Department of Physiology, Michigan State University, East Lansing, MI 48824Department of Physiology, Michigan State University, East Lansing, MI 48824Department of Nutrition and Exercise Sciences, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331To whom correspondence should be addressed; Department of Physiology, Michigan State University, East Lansing, MI 48824Enhanced production of monounsaturated fatty acids (FA) derived from carbohydrate-enriched diets has been implicated in the development of obesity and insulin resistance. The FA elongases Elovl-5 and Elovl-6 are regulated by nutrient and hormone status, and have been shown using intact yeast and mammalian microsome fractions to be involved in the synthesis of monounsaturated FAs (MUFA). Herein, targeted knockdown and overexpression of Elovl-5 or Elovl-6 was used to determine their roles in de novo synthesis of specific MUFA species in mammalian cells. Treatment of rat insulinoma (INS)-1 cells with elevated glucose increased de novo FA synthesis and the ratio of MUFAs to saturated FAs. Elovl-5 knockdown decreased elongation of 16:1,n-7. Elovl-5 overexpression increased synthesis of 18:1,n-7; however, this increase was dependent on stearoyl-CoA desaturase–driven 16:1,n-7 availability. Knockdown of Elovl-6 decreased elongation of 16:0 and 16:1,n-7, resulting in accumulation of 16:1,n-7. Elovl-6 overexpression preferentially drove synthesis of 16:0 elongation products 18:0 and 18:1,n-9 but not 18:1,n-7. These findings demonstrate that coordinated induction of FA elongase and desaturase activity is required for balanced synthesis of specific n-7 versus n-9 MUFA species. Given the relative abundance of 16:0 to 16:1,n-7 and the specificity of Elovl-6 for 16:0, Elovl-6 is a major elongase for 18:1,n-9 production.http://www.sciencedirect.com/science/article/pii/S0022227520371091fatty acid synthesisstearoyl-CoA desaturasepalmitoleateoleatevaccinatepalmitate |
| spellingShingle | Christopher D. Green Cansel G. Ozguden-Akkoc Yun Wang Donald B. Jump L. Karl Olson Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species[S] Journal of Lipid Research fatty acid synthesis stearoyl-CoA desaturase palmitoleate oleate vaccinate palmitate |
| title | Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species[S] |
| title_full | Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species[S] |
| title_fullStr | Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species[S] |
| title_full_unstemmed | Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species[S] |
| title_short | Role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species[S] |
| title_sort | role of fatty acid elongases in determination of de novo synthesized monounsaturated fatty acid species s |
| topic | fatty acid synthesis stearoyl-CoA desaturase palmitoleate oleate vaccinate palmitate |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520371091 |
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