Srebp Expression On Fatty Acid Metabolism In Vitamin A deficient liver

QUIROGA, C.; ANZULOVICH A.C.; BONOMI M.R.; OLIVEROS L; GIMÉNEZ MS

Mar del Plata, Bs. As.

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

SAIB

We know that vit A deficiency decreases liver Acetyl CoA Carboxylase (ACC-L) activity, which is involved in malonyl-CoA formation. Here we determine the mRNA levels of ACC-L, Fatty Acid Synthetase (FAS), Carnitine Palmitoyltransferase I (CPT-I), a key enzyme in fatty acid beta-oxidación, and SREBP-1c, a key transcription factor that regulates lipid enzyme genes. Also, mitochondrial CPT-I activity was measured.Wistar female rats at 21 d age were weaned onto either a vitAdeficient diet (-A) or the same diet with 8 mg retinol/kg diet (control). They were fed for 3 months. Also, a -A group was refed for 15 days with control diet (-A refed). Serum and liver VitAwas measured by HPLC. Liver mRNAlevels were determined by RT-PCR, and CPT-I activity, by using [ C]carnitine as substrate. Statistical analysis was performed by ANOVA. In -A rats the mRNAexpression of SREBP-1c decreased, compared to control. This was associated to a decrease in ACC and FAS mRNA levels (p< 0.01) due to SREBP-1c regulation of gene expression . Vit A deficiency increased the mRNA levels and activity of CPT-I (p< 0.001). Vit A restitution to the diet reversed mRNA levels and enzyme activity. The changes in ACC suggest a low availability of malonyl-CoA, endogenous inhibitor of CPT I, that could produce a stimulation of the fatty acid -oxidation process. Vit A regulates hepatic fatty acids synthesis and degradation.