Inserted n6 to n3 fat gene alters n3:n6 bal from 1:15 to 1:1
 

For those of you who have been following the "fats" debate. Rat heart cells were gentically modified to allow them to change omega sixes to omega threes and then provided with n3 and n6 in a ratio of about 1:15. This was the result.....

"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."

Is this evidence that at least in the heart the body if left to its own devices might select a omega three six balance of 1:1.

Significant down regulation of eicsanoid products was noted (expression item shown reduced between 4 and five times)

Interesting!

RB



http://www.pnas.org/cgi/content/abst...e2=tf_ipsecsha


ABSTRACT


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



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@mgh.harvard.edu.

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