Va. Mustad et al., DIETARY LINOLEIC-ACID INCREASES AND PALMITIC ACID DECREASES HEPATIC LDL RECEPTOR PROTEIN AND MESSENGER-RNA ABUNDANCE IN YOUNG-PIGS, Journal of lipid research, 37(11), 1996, pp. 2310-2323
The present study was conducted to determine tile effects of dietary f
atty acids on hepatic LDL receptor (LDLr) protein abundance and mRNA l
evels. 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 ac
id or linoleic acid. A control group was fed the base diet with no add
ed fat. After 30 days, plasma LDL-cholesterol (LDL-C) levels increased
as the dietary cholesterol increased (P < 0.05); however, there was n
o significant effect of either fatty acid. Dietary fatty acids, howeve
r, had distinctly different effects on hepatic LDLr protein (analysed
by ELISA) and mRNA (analysed by Northern blot) abundance. When pigs co
nsumed diets containing 0.25% cholesterol, linoleic acid increased hep
atic 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 dif
ferential effects of fatty acids on LDLr expression were only observed
at 0.25% cholesterol, suggesting that higher intakes of cholesterol h
ave 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 sum
mary, our results indicate that dietary linoleic acid and palmitic aci
d have markedly different effects on hepatic LDLr protein abundance th
at are mediated by differential effects on LDLr mRNA levels. Further s
tudies are needed to fully elucidate the molecular mechanisms by which
fatty acids regulate LDLr mRNA and protein levels.