Expression of liver carnitine palmitoyltransferase I and II genes during development in the rat

Abstract

The enzyme activity and the expression (protein and mRNA concentrations) of genes encoding for hepatic carnitine palmitoyl-transferases (CPT) I and II were studied during neonatal development, in response to nutritional state at weaning and during the fed-starved transition in adult rats. The activity, the protein concentration and the level of mRNA encoding CPT I are low in foetal-rat liver and increase 5-fold during the first day of extra-uterine life. The activity and gene expression of CPT I are high during the entire suckling period, in the liver of 30-day-old rats weaned at 20 days on to a high-fat diet and in the liver of 48 h-starved adult rats. The activity and CPT I gene expression are markedly decreased in the liver of rats weaned on to a high-carbohydrate diet. By contrast, the activity, the protein concentration and the level of mRNA encoding CPT II are already high in the liver of term foetuses and remain at this level throughout the suckling period, irrespective of the nutritional state of the animals either at weaning or in the adult.

Role of insulin in hepatic fatty acid partitioning: emerging concepts

“…Incubation of cultured foetal rabbit hepatocytes with long-chain fatty acids also induces the expression of CPT I [64]. Similarly, studies on neonatal-rat liver have shown that the increase in insulin\glucagon concentration ratio that accompanies weaning of the pups on to a highcarbohydrate diet is accompanied by a rapid decline in the CPT I mRNA content, but not in that of CPT II [65]. Interestingly, the expression of CPT I protein showed a much more gradual decline than that of its mRNA, indicating that the protein has a long half-life.…”

Cloning and characterization of the promoter for the liver isoform of the rat carnitine palmitoyltransferase I (L-CPT I) gene

“…The human CPT II promoter contains a TATA box [14] but the mouse gene has no TATA box [13]. However, it would be anticipated that the promoters of the L-CPT I and CPT II genes should be different since the CPT II gene is expressed in all tissues and is not subject to hormonal or developmental control [18,20]. The human M-CPT I promoter also appears to be different as it utilizes two alternatively expressed first exons [10].…”

“…There is considerable evidence for the presence of additional CPT activities in peroxisomes and microsomes based upon cDNA cloning, protein purification and antibody studies [15][16][17]. L-CPT I gene expression and enzyme activity increase dramatically in the liver at birth [18]. With weaning to a high fat diet, transcription of L-CPT I remains high while weaning to a high carbohydrate diet results in diminished L-CPT I expression [18].…”

“…L-CPT I gene expression and enzyme activity increase dramatically in the liver at birth [18]. With weaning to a high fat diet, transcription of L-CPT I remains high while weaning to a high carbohydrate diet results in diminished L-CPT I expression [18]. These observations suggest an important role for hormones and diet in controlling L-CPT I expression.…”

“…Following birth, L-CPT I activity in the heart declines while the abundance of the muscle isoform increases [21]. CPT II is expressed before birth and its activity and mRNA abundance are unchanged by fatty acids or insulin [18,19]. Only clofibrate is able to stimulate CPT II gene expression [19].…”