Cadmium suppresses Δ9 desaturase activity in rat hepatocytes

Abstract

The effects of cadmium (Cd) on the fatty acid composition and Δ9 desaturation activity were studied in hepatocytes which had been cultured in serum-free medium. The aim of this study was to determine whether the inhibition of Δ9 desaturase seen in Cd-treated rat liver (Kudo et al. (1991) Toxicology, 68, 133–142) is the direct effect of Cd or not. When hepatocytes were cultured in serum-free medium, increases in the proportions of monounsaturated fatty acids such as oleic acid (18:1) were observed in the phospholipid (PL) and triacylglycerol (TG) fractions of hepatocytes, suggesting that Δ9 desaturase was induced. By contrast, essential fatty acids such as linoleic acid (18:2) and arachidonic acid (20:4) decreased. These changes were similar to those seen in the livers of essential fatty acid (EFA)-deficient rats. When hepatocytes were cultured in the presence of CdCl 2, the changes in the fatty acid composition were suppressed. The effect of CdCl 2 was concentration-dependent. The rate of the conversion of 18:0 to 18:1, which is catalyzed by Δ9 desaturase, was reduced by treatment with Cd, whereas the rate of conversion of 18:2 to 20:4, which is catalyzed by Δ6 desaturase, was slightly increased. Cd did not inhibit liver microsomal Δ9 desaturase activity in vitro. We concluded that Cd suppressed the induction of Δ9 desaturase in cultured hepatocytes. These phenomena can explain the selective inhibition of Δ9 desaturase in the livers of Cd-treated rats.