The expression of Apoc3 mRNA is regulated by HNF4α and COUP‐TFII levels, but not retinoid treatments, in rat primary hepatocytes and hepatoma cells

Abstract

Retinoic acid (RA) treatment induces hyperlipidemia in humans and animals. This has been attributed to the induction of Apolipoprotein CIII (gene, Apoc3), which inhibits lipoprotein lipase activity. We have shown that vitamin A status and retinoid treatment regulate hepatic lipogenic gene expression, suggesting that the induction of lipogenic genes, but not Apoc3, may contribute to hyperlipidemia. To test this, we analyzed the expression levels of Apoc3 mRNA in response to retinoid treatments or adenovirus‐mediated over‐expression of nuclear receptors mediating RA responses in primary rat hepatocytes and HL1C rat hepatoma cells using real‐time PCR. We report that retinoids did not induce Apoc3 mRNA expression in these cells. The over‐expression of HNF4α or COUP‐TFII significantly induced or inhibited the Apoc3 mRNA level, respectively, whereas RXRα or RARα over‐expression had no effect. We conclude that RA treatment could not directly induce Apoc3 mRNA levels in rat hepatocytes. Instead, the hepatic expression of Apoc3 mRNA is regulated by the expression levels of HNF4α and COUP‐TFII. Therefore, RA‐induced hyperlipidemia may not be attributed to the direct induction of Apoc3 mRNA level in hepatocytes.Sponsor: Dr. Guoxun Chen, 1215 W. Cumberland Ave. 229 Jessie Harris Building, Knoxville, TN, 37996