Primary rodent hepatocytes and
hepatoma cell lines are commonly used as model systems to elucidate and study potential drug targets for
metabolic diseases such as
obesity and
atherosclerosis. However, if
therapies are to be developed, it is essential that our knowledge gained from these systems is translatable to that of human. Here, we have characterized
lipid and
lipoprotein metabolism in primary human hepatocytes for comparison to rodent primary hepatocytes and human
hepatoma cell lines. Primary human hepatocytes were maintained in
collagen coated dishes in confluent monolayers for up to 3 days. We found primary human hepatocytes were viable, underwent
lipid synthesis, and were able to secret
lipoproteins up to 3 days in culture. Furthermore, the
lipoprotein profile secreted by primary human hepatocytes was comparable to that found in human plasma; this contrasts with primary rodent hepatocytes and human
hepatoma cells. We also investigated the pharmacological effects of
nicotinic acid (
niacin, NA), a potent dyslipidemic drug, on hepatic
lipid synthesis and
lipoprotein secretion. We found NA increased the expression of
ATP-binding cassette transporter A1 in primary human hepatocytes, which may potentially explain how NA increases plasma
high-density lipoproteins in humans. In conclusion, primary human hepatocytes are a more relevant model to study
lipid synthesis and
lipoprotein secretion than
hepatoma cells or rodent primary hepatocyte models. Further research needs to be done to maintain liver specific functions of primary human hepatocytes in prolonged cultures for these cells to be a viable model.