Apolipoprotein b transcription is driven by ornithine in hepatoma cell lines

The liver is a central metabolic organ, and nutritional status, such as protein/amino acid malnutrition, significantly affects metabolic homeostasis. When animals are fed an amino acid-restricted diet, triglyceride-rich very low-density lipoprotein (VLDL) secretion is lowered, leading to fatty liver development. Therefore, we have explored the effects of amino acids on the expression of Apolipoprotein b (Apob), the main VLDL component, using a hepatoma cell culture model. When H4IIE rat hepatoma cells were cultured in an amino acid-depleted medium, Apob mRNA levels were significantly lower than those in control cells. In addition, when cells were cultured in media deprived of a single amino acid, aspartic or glutamic acid deprivation decreased Apob mRNA levels, whereas depletion of lysine, histidine, threonine, leucine, or isoleucine increased it. To understand the interrelationship between these extracellular amino acids and Apob transcription, metabolome analysis of these cells was performed. The intracellular methionine, adenine, and ornithine levels were positively correlated with Apob mRNA levels. Among them, only ornithine significantly enhanced Apob transcription, when added to the amino acid-depleted medium. In summary, these results suggest that ornithine plays a key role in Apob transcriptional regulation, corresponding to changes in extracellular amino acid concentrations.