Study on possible mechanism of orotic acid-induced fatty liver in rats.

OBJECTIVE

The aim of this study was to investigate the possible mechanism of orotic acid-induced fatty liver in rats.

METHODS

Rats were randomly divided into two groups and fed an AIN-93 diet with 1% orotic acid or without orotic acid for 10 d. Hepatic lipid concentrations, such as triacylglycerol, total cholesterol, and phospholipids, were examined. To clarify the mechanism of orotic acid-induced fatty liver, hepatic enzyme activities and mRNA levels of key enzymes related in lipid metabolism and hepatic gene expression of transcription factors were determined.

RESULTS

Orotic acid administration significantly increased hepatic triacylglycerol concentration. The activity and mRNA level of fatty acid synthase were obviously upregulated by orotic acid treatment, whereas the activities and mRNA concentrations of carnitine palmitoyl transferase and microsomal triacylglycerol transfer protein were significantly depressed. Furthermore, orotic acid stimulated the mRNA expression of sterol regulatory element binding protein-1c but did not alter the mRNA concentration of peroxisome proliferator-activated receptor-α in the liver.

CONCLUSION

The stimulation of triacylglycerol synthesis induced by orotic acid is mainly caused by enhancement of sterol regulatory element binding protein-1c and its target gene involved in fatty acid biosynthesis. In contrast, the inhibition of fatty acid β-oxidation and very-low-density lipoprotein secretion were related to the observed lipid accumulation.