[Nutritional regulation of apolipoprotein genes. Effect of dietary carbohydrates and fatty acids]. / Régulation nutritionnelle des gènes d'apolipoprotéines. Effet des hydrates de carbone et des acides gras alimentaires.

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 A1 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 A1 synthesis and secretion without any modification in apo A1 mRNA. In contrast, the hepatocytes exhibit a concomitent decrease in apo E synthesis and secretion and in cellular apo E mRNA levels.

Effect of dietary fish oil and corn oil on lipid metabolism and apolipoprotein gene expression by rat liver.

A 3-week fish oil diet induced in weanling rats a decrease in plasma lipids and liver triacylglycerol, and an increase in insulinemia, compared to a corn oil diet. At the same time, plasma apolipoprotein (apo) A-I was slightly lower and plasma heavy apo B/light apo B ratio was higher in fish-oil-fed than in corn-oil-fed rats. Hepatocytes obtained from fish-oil-fed and corn-oil-fed rats were used to examine how fish oil affects lipid and apolipoprotein synthesis and secretion. Primary culture of hepatocytes from fish-oil-fed rats displayed a lower ability to synthesize and secrete triacylglycerol than hepatocytes from corn-fed rats, as measured by mass determination or [U-14C]glycerol incorporation. Hepatocytes from fish-oil-fed rats exhibited a lower synthesis of cholesterol, measured by [14C]acetate incorporation, than hepatocytes from corn-oil-fed rats. This impairment was associated with an increase in beta-oxidation, a higher channeling of oleic acid into phospholipids, and a lower triacylglycerol/diacylglycerol ratio in hepatocytes from fish-oil-fed rats than in hepatocytes from corn-oil-fed rats. Incorporation of [35S]methionine into secreted apoB was reduced in hepatocytes from fish-oil-fed rats, but was not paralleled by a decrease in apo B mRNA. The appearance of degradative forms of apo B suggest an increase in apo B degradation in hepatocytes from fish-oil-fed rats. Incorporation of [35S]methionine into cellular and secreted apo A-I was lower in hepatocytes from fish-oil-fed rats than in hepatocytes from corn-oil-fed rats, and was not paralleled by any difference in the apo A-I mRNA level. Finally, [35S]methionine incorporation into cellular and secreted forms of apo E and apo A-I mRNA were reduced in hepatocytes from fish-oil-fed rats, compared with hepatocytes from corn-oil-fed rats. These combined data show that fish oil diet reduces triacylglycerol synthesis and secretion and affects apo B synthesis at a post-transcriptional level, and reduces cholesterol synthesis and affects apo E and apo A-I synthesis at a transcriptional and a post-transcriptional level.