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 development. Iron related dysregulation of hepatic genes could play a role in this phenomenon. We previously found that the carbonyl-iron overloaded mouse was a useful model to study the mechanisms involved in the development of hepatic lesions related to iron excess. The aim of the present study was to identify hepatic genes overexpressed in conditions of iron overload by using 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 increased. In addition, we demonstrated that both SCD1 mRNA expression and activity were increased in another iron overload model in mice obtained by a single iron-dextran subcutaneous injection. Moreover, we found, in both models, 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 upregulation was not detected in earlier stages of iron overload. In addition, we found that cellular repartition likely influenced SCD1 mRNA expression. In conclusion, we demonstrated that iron excess in the liver induced both the expression 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 expression and activity of SCD1, an enzyme adding a double bound into saturated fatty 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 unsaturated fatty acids.
Unité d'Etude des Régulations des Equilibres Fonctionnels du Foie Normal et Pathologique, INSERM U522, Rennes, France. christelle.pigeon@rennes.inserm.fr
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C
Pigeon
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Legrand
P
P
Leroyer
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Bouriel
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B
Turlin
P
P
Brissot
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Loréal
D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D054354:Iron Carbonyl Compounds; D019190:Iron Overload / Q000378:metabolism*; D007505:Iron-Dextran Complex; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds; D012333:RNA, Messenger / Q000032:analysis; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D009942:Organometallic Compounds; D012333:RNA, Messenger; D054354:Iron Carbonyl Compounds; D007505:Iron-Dextran Complex; D013230:Stearoyl-CoA Desaturase