Nutritional regulation of apolipoprotein genes: effect of dietary carbohydrates and fatty acids.

The effect of nutritional factors on apolipoprotein gene expression by rat liver were studied. Dietary carbohydrates or fatty acids regulate the expression of apo E gene, by altering either gene transcription or mRNA stability. Conversely, apo AI regulation occurs at a post transcriptional level. In vivo and in vitro experiments gave contradictory results concerning apo B gene expression. The more dramatic changes in plasma lipids and apolipoproteins are obtained under dietary fish oil. Hepatocytes from fish oil-fed rats retain for several days modification in fatty acid metabolism, i.e. a shift in oleic acid channeling towards oxidation at the expense of esterification and a reduced ability to synthesize and secrete triacylglycerol. These modifications are paralleled with a decrease in the synthesis and in the secretion of apo Bs. Hepatocytes from fish oil fed rats secrete degradative forms of apo B which might result from either a sluggish VLDL synthesis and secretion or a more specific effect of n-3 long chain polyunsaturated fatty acid peroxidative products. Hepatocytes from fish oil fed rats exhibit a reduced ability to synthesize cholesterol, associated with a decrease in apo AI synthesis and secretion without any modification in apo AI mRNA. In contrast, the hepatocytes exhibit a concomitent decrease in apo E synthesis and secretion and in cellular apo E mRNA levels.