Zb. Kang et al., Adenoviral gene transfer of Caenorhabditis elegans n-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells, P NAS US, 98(7), 2001, pp. 4050-4054
Citations number
27
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Omega-3 polyunsaturated fatty acids (PUFAs) are essential components requir
ed for normal cellular function and have been shown to exert many preventiv
e 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 funct
ions; their balance is important for homeostasis and normal development. El
evating tissue concentrations of n-3 PUFAs in mammals relies on chronic die
tary intake of fat rich in n-3 PUFAs, because mammalian cells lack enzymati
c activities necessary either to synthesize the precursor of n-3 PUFAs or t
o convert n-6 to n-3 PUFAs. Here we report that adenovirus-mediated introdu
ction of the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid d
esaturase into mammalian cells can quickly and effectively elevate the cell
ular n - 3 PUFA contents and dramatically balance the ratio of n-6/n-3 PUFA
s, Heterologous expression of the fat-1 gene in rat cardiac myocytes render
ed cells capable of converting various n-6 PUFAs to the corresponding n-3 P
UFAs, 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 sign
ificantly in the transgenic cells. This study demonstrates an effective app
roach to modifying fatty acid composition of mammalian cells and also provi
des a basis for potential applications of this gene transfer in experimenta
l and clinical settings.