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Adenoviral Gene Transfer of Caenorhabditis elegans n-3 Fatty Acid Desaturase Optimizes Fatty Acid Composition in Mammalian Cells
Zhao B. Kang, Yinlin Ge, Zhihong Chen, Joanne Cluette-Brown, Michael Laposata, Alexander Leaf and Jing X. Kang
Proceedings of the National Academy of Sciences of the United States of America
Vol. 98, No. 7 (Mar. 27, 2001), pp. 4050-4054
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3055368
Page Count: 5
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Omega-3 polyunsaturated fatty acids (PUFAs) are essential components required for normal cellular function and have been shown to exert many preventive and therapeutic actions. The amount of n-3 PUFAs is insufficient in most Western people, whereas the level of n-6 PUFAs is relatively too high, with an n-6/n-3 ratio of > 18. These two classes of PUFAs are metabolically and functionally distinct and often have important opposing physiological functions; their balance is important for homeostasis and normal development. Elevating tissue concentrations of n-3 PUFAs in mammals relies on chronic dietary intake of fat rich in n-3 PUFAs, because mammalian cells lack enzymatic activities necessary either to synthesize the precursor of n-3 PUFAs or to convert n-6 to n-3 PUFAs. Here we report that adenovirus-mediated introduction of the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase into mammalian cells can quickly and effectively elevate the cellular n-3 PUFA contents and dramatically balance the ratio of n-6/n-3 PUFAs. Heterologous expression of the fat-1 gene in rat cardiac myocytes rendered cells capable of converting various n-6 PUFAs to the corresponding n-3 PUFAs, and changed the n-6/n-3 ratio from about 15:1 to 1:1. In addition, an eicosanoid derived from n-6 PUFA (i.e., arachidonic acid) was reduced significantly in the transgenic cells. This study demonstrates an effective approach to modifying fatty acid composition of mammalian cells and also provides a basis for potential applications of this gene transfer in experimental and clinical settings.
Proceedings of the National Academy of Sciences of the United States of America © 2001 National Academy of Sciences