ALTERED REGULATION OF APOLIPOPROTEIN A-IV GENE-EXPRESSION IN THE LIVER OF THE GENETICALLY-OBESE ZUCKER RAT

apolipoprotein (apo) A-IV, a structural component of chylomicrons and high-density lipoproteins, may play a role in the catabolism of trigyc eride-rich lipoproteins and in reverse cholesterol transport. To study the regulation of apoA-IV gene expression by genetic and nutritional factors, we determined the effect of a fish oil-rich and a sucrose-ric h diet on apoA-IV gene transcription and nuclear and total cellular ap oA-IV mRNA abundance in livers of genetically obese, hyperlipoproteine mic (fa/fa) Zucker rats and their lean (Fa/-) littermates. In obese ra ts fed chow, hepatic apoA-IV gene expression was more than twofold hig her than in lean rats because of a post-transcriptional mechanism. apo A-1 gene expression and apoC-III mRNA levels, studied as controls, wer e similar in both groups. The fish oil-rich diet reduced total cellula r apoA-IV mRNA abundance transcriptionally to 34+/-4% of basal values in lean rats, but did not alter apoA-IV gene expression in obese rats. In contrast, this diet reduced apoA-1 gene expression in both lean an d obese animals. The sucrose-rich diet increased apoA-IV gene expressi on twofold in both lean and obese rats. Thus, genetic obesity alters t he response of hepatic apoA-IV gene expression to a lipid-lowering die t rich in fish oil by a mechanism affecting transcriptional regulation .