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 triglyceride-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-rich diet on apoA-IV gene transcription and nuclear and total cellular apoA-IV mRNA abundance in livers of genetically obese, hyperlipoproteinemic (fa/fa) Zucker rats and their lean (Fa/-) littermates. In obese rats fed chow, hepatic apoA-IV gene expression was more than twofold higher than in lean rats because of a post-transcriptional mechanism. apoA-I gene expression and apoC-III mRNA levels, studied as controls, were similar in both groups. The fish oil-rich diet reduced total cellular 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-I gene expression in both lean and obese animals. The sucrose-rich diet increased apoA-IV gene expression twofold in both lean and obese rats. Thus, genetic obesity alters the response of hepatic apoA-IV gene expression to a lipid-lowering diet rich in fish oil by a mechanism affecting transcriptional regulation.
Strobl
W
W
Department of Pediatrics, University of Vienna, Austria.
Knerer
B
B
Gratzl
R
R
Arbeiter
K
K
Lin-Lee
Y C
YC
Patsch
W
W
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000235:genetics; D001054:Apolipoproteins A / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D004041:Dietary Fats; D005395:Fish Oils; D012333:RNA, Messenger; C022205:apolipoprotein A-IV