Nutritional regulation of visceral markers in rat liver and cultured hepatoma cells

Protein malnutrition in humans and other animals is consistently associated with a decreased concentration of circulating serum albumin, transthyretin (TTR), and insulin-like growth factor-I (IGF-I). The molecular mechanisms for regulation of the three polypeptides by dietary protein remain to be completely elucidated. The abundance of albumin, TTR and IGF-I mRNA is decreased in liver of juvenile rats consuming insufficient amounts of protein. Moreover, protein restriction specifically decreases the abundance of albumin and TTR nuclear transcripts, indicating that the reduction in mRNA levels for these two genes is caused at least partly by a decrease in gene transcription. Expression of several other genes transcribed at a high level in the liver is also decreased under conditions of dietary protein restriction, suggesting that the level/functional activity of liver-enriched transcription factor(s) might be decreased under these conditions. Limitation of cultured hepatoma cells for a single amino acid also selectively decreases the mRNA levels of several genes with liver-enriched expression, including albumin and TTR. The decrease in albumin mRNA is caused partly by decreased albumin gene transcription and partly by destabilization of albumin mRNA.