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, Jing X. Kang

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4050-4054
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number7
DOIs
StatePublished - Mar 27 2001
Externally publishedYes

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Fatty Acid Desaturases
Caenorhabditis elegans
Omega-3 Fatty Acids
Fatty Acids
Unsaturated Fatty Acids
Genes
Fats
Eicosanoids
Dietary Fats
Cardiac Myocytes
Arachidonic Acid
Adenoviridae
Mammals
Homeostasis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Adenoviral gene transfer of Caenorhabditis elegans n-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells. / Kang, Zhao B.; Ge, Yinlin; Chen, Zhihong; Cluette-Brown, Joanne; Laposata, Michael; Leaf, Alexander; Kang, Jing X.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 7, 27.03.2001, p. 4050-4054.

Research output: Contribution to journalArticle

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