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Journal of Lipid Research, Vol 37, 2310-2323, Copyright © 1996 by Lipid Research, Inc.
VA Mustad, JL Ellsworth, AD Cooper, PM Kris-Etherton and TD Etherton
The present study was conducted to determine the effects of dietary fatty
acids on hepatic LDL receptor (LDLr) protein abundance and mRNA levels.
Sixty pigs were randomized into 10 groups and fed corn-soybean meal diets
containing three cholesterol levels (0.25%, 0.5%, and 1.0%, w/w) with no
added fat, or fats rich (30% of calories) in palmitic acid or linoleic
acid. A control group was fed the base diet with no added fat. After 30
days, plasma LDL-cholesterol (LDL-C) levels increased as the dietary
cholesterol increased (P < 0.05); however, there was no significant
effect of either fatty acid. Dietary fatty acids, however, had distinctly
different effects on hepatic LDLr protein (analyzed by ELISA) and mRNA
(analyzed by Northern blot) abundance. When pigs consumed diets containing
0.25% cholesterol, linoleic acid increased hepatic LDLr protein 40% whereas
palmitic acid reduced it 40% (P < 0.05). These changes in LDLr protein
abundance were accompanied by parallel changes in hepatic LDLr mRNA;
linoleic acid increased LDLr mRNA 2-fold (P < 0.01), whereas palmitic
acid decreased it 60% (P < 0.01). The differential effects of fatty
acids on LDLr expression were only observed at 0.25% cholesterol,
suggesting that higher intakes of cholesterol have a dominant and
repressive effect on regulation of LDLr expression. Cholesterol intake
increased hepatic total cholesterol levels (P < 0.01) while dietary
fatty acids had no effect on hepatic sterols. In summary, our results
indicate that dietary linoleic acid and palmitic acid have markedly
different effects on hepatic LDLr protein abundance that are mediated by
differential effects on LDLr mRNA and protein levels. Further studies are
needed to fully elucidate the molecular mechanisms by which fatty acids
regulate LDLr mRNA and protein levels.
ARTICLES
Dietary linoleic acid increases and palmitic acid decreases hepatic LDL receptor protein and mRNA abundance in young pigs
Graduate Program in Nutrition, Pennsylvania State University, University Park 16802, USA.
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