Conversion of hexadecanoic acid to hexadecenoic acid by rat 6-desaturase

A higher content of C16:1 n-10 has recently been reported in the preputial gland of mice with a targeted disruption of the gene encoding stearoyl-CoA desaturase 1 (SCD1 / mice) when compared with wild-type mice. This result has provided the first physiological evidence for the presence and regulation of a palmitoyl-CoA 6-desaturase in mammals. To investigate the putative involvement of the known 6-desaturase (FADS2) in this process, COS-7 cells expressing rat 6-desaturase were incubated with C16:0. Transfected cells were able to synthesize C16:1 n-10, while nontransfected cells did not produce any C16:1 n-10. Evidence is therefore presented that the rat 6-desaturase, which acts on the 18and 24-carbon fatty acids of the n-6 and n-3 series, is also able to catalyze palmitic acid 6-desaturation. —Guillou, H., V. Rioux, D. Catheline, J-N. Thibault, M. Bouriel, S. Jan, S. D’Andrea, and P. Legrand. Conversion of hexadecanoic acid (palmitic acid, C16:0) to hexadecenoic acid (C16:1 n-10) by rat 6-desaturase. J. Lipid Res. 2003. 44: 450–454. Supplementary key words desaturation • saturated fatty acids • FADS2 • animal The presence of a palmitoyl-CoA 6-desaturase has recently been described in mice (1). This unexpected 6-desaturase activity was found in mice deficient for stearoyl-CoA desaturase 1 (SCD1 / mice). However, this palmitoyl-CoA 6-desaturase activity has not yet been ascribed to any known desaturase gene. The 6-desaturase (FADS2) has been cloned in several mammalian species (2, 3). In a previous work (4), we reported that recombinant rat 6-desaturase expressed in COS-7 cells acts on 18and 24-carbon fatty acids of the n-3 and n-6 series in polyunsaturated fatty acid (PUFA) biosynthesis. This result, consistent with experiments performed in yeast (5) and the PUFA biosynthetic pathway initially proposed by Sprecher and coworkers (6), illustrated the broad chain length specificity of the 6-desaturase. In the present work, we investigated the putative involvement of FADS2 protein in the 6-desaturation of palmitic acid. We established that C16:0 is desaturated to C16:1 n-10 by COS-7 cells when expressing rat 6-desaturase. Moreover, coexpression of both 6-desaturase and SCD1 resulted in both 6and 9-desaturation of palmitic acid. Therefore, this study reports for the first time that a single gene encodes a mammalian 6-desaturase that acts on one saturated fatty acid in addition to act on PUFAs. MATERIALS AND METHODS