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Published online on March 20, 2001, 10.1073/pnas.061040198
PNAS | March 27, 2001 | vol. 98 | no. 7 | 4050-4054


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Medical Sciences
 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-Browndagger , Michael Laposatadagger , Alexander Leaf*, and Jing X. Kang*,Dagger

Departments of * Medicine and dagger  Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114

Contributed by Alexander Leaf, January 24, 2001

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.

Dagger To whom reprint requests should be addressed at: Massachusetts General Hospital, Room 4433, 149 13th Street, Charlestown, MA 02129. E-mail: kang.jing{at}mgh.harvard.edu.

www.pnas.org/cgi/doi/10.1073/pnas.061040198
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