Stearoyl coenzyme A desaturase 1 expression and activity are increased in the liver during iron overload

In humans, hepatic iron overload can lead to hepatocellular carcinoma devel opment. Iron related dysregulation of hepatic genes could play a role in th is phenomenon. We previously found that the carbonyl-iron overloaded mouse was a useful model to study the mechanisms involved in the development of h epatic lesions related to iron excess. The aim of the present study was to identify hepatic genes overexpressed in conditions of iron overload by usin g this model. A suppressive subtractive hybridization was performed between hepatic mRNAs extracted from control and 3% carbonyl-iron overloaded mice during 8 months. This methodology allowed us to identify stearoyl coenzyme A desaturase 1 (SCD1) mRNA overexpression in the liver of iron loaded mice. The corresponding enzymatic activity was also found to be significantly in creased. In addition, we demonstrated that both SCD1 mRNA expression and ac tivity were increased in another iron overload model in mice obtained by a single iron-dextran subcutaneous injection. Moreover, we found, in both mod els, that SCD1 mRNA was not only influenced by the quantity of iron in the liver but also by the duration of iron overload since SCD1 mRNA upregulatio n was not detected in earlier stages of iron overload. In addition, we foun d that cellular repartition likely influenced SCD1 mRNA expression. In conc lusion, we demonstrated that iron excess in the liver induced both the expr ession of SCD1 mRNA and its corresponding enzymatic activity. The level and duration of iron overload, as well as cellular repartition of iron excess in the liver likely play a role in this induction. The fact that the expres sion and activity of SCD1, an enzyme adding a double bound into saturated f atty acids, are induced in two models of iron overload in mice leads to the conclusion that iron excess in the liver may enhance the biosynthesis of u nsaturated fatty acids. (C) 2001 Elsevier Science B.V. All rights reserved.