Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein

Different dietary fatty acids exert specific effects on plasma lipids but the mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol diets containing triacylglycerols enriched in specific saturated fatty acids, and effects on plasma lipids and the expression of genes involved in hepatic lipoprotein metabolism were measured. Trimyristin and tripalmitin caused significant rises in low-density lipoprotein (LDL) cholesterol which were accompanied by significant reductions in hepatic LDL receptor mRNA levels. Tripalmitin also increased hepatic expression of the apolipoprotein B gene, implying an increased production of LDL via very-low-density lipoprotein (VLDL) and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not vary significantly between the groups. Compared with triolein, tristearin had little effect on hepatic gene expression or total plasma cholesterol. However, it caused a marked decrease in VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary stearate. The differential changes in plasma lipids and hepatic mRNA levels induced by specific dietary fats suggests a role for fatty acids or a metabolite thereof in the regulation of the expression of genes involved in lipoprotein metabolism.

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Low Density Lipoprotein Metabolism and ?3 Fatty Acids

Effects of Fatty Acids and Lipids in Health and Disease - World Review of Nutrition and Dietetics ◽

10.1159/000423984 ◽

2015 ◽

pp. 30-33

Author(s):

K. C. Hayes

Keyword(s):

Fatty Acids ◽

Low Density Lipoprotein ◽

Lipoprotein Metabolism ◽

Density Lipoprotein ◽

Low Density

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The role of fatty acid saturation on plasma lipids, lipoproteins, and apolipoproteins: II. The plasma total and low-density lipoprotein cholesterol response of individual fatty acids

Metabolism ◽

10.1016/0026-0495(93)90183-o ◽

1993 ◽

Vol 42 (1) ◽

pp. 130-134 ◽

Cited By ~ 42

Author(s):

Janice Derr ◽

P.M. Kris-Etherton ◽

Thomas A. Pearson ◽

Frances H. Seligson

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Plasma Lipids ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Fatty Acid Saturation

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Effect of simvastatin on plasma lipid and lipoprotein concentrations and low-density lipoprotein metabolism in the nephrotic syndrome

Clinical Science ◽

10.1042/cs0820701 ◽

1992 ◽

Vol 82 (6) ◽

pp. 701-708 ◽

Cited By ~ 15

Author(s):

G. L. Warwick ◽

C. J. Packard ◽

L. Murray ◽

D. Grierson ◽

J. P. Stewart ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Apolipoprotein B ◽

Cholesterol Synthesis ◽

Low Density Lipoprotein ◽

Plasma Lipid ◽

Lipoprotein Metabolism ◽

Density Lipoprotein ◽

Cholesterol Concentration ◽

Low Density ◽

Coa Reductase

1. The effect of inhibiting the rate-limiting enzyme (3-hydroxy-3-methylglutaryl-CoA reductase, EC 1.1.1.88) in cholesterol synthesis on plasma lipid and lipoprotein concentrations was investigated in 16 patients with primary glomerular disease, heavy proteinuria, well-preserved renal function and hypercholesterolaemia. 2. Detailed studies of low-density lipoprotein metabolism were performed on eight patients before and after 12 weeks of simvastatin therapy. Radioiodinated tracers were used to quantify the fractional catabolic rate of low-density lipoprotein by apolipoprotein B/E receptors and alternative pathways. 3. Simvastatin produced consistent reductions in total plasma cholesterol concentration (median 36.9%), plasma low-density lipoprotein-cholesterol concentration (43.6%) and apolipoprotein B pool size (29.9%). 4. In contrast, the changes in kinetic parameters of low-density lipoprotein metabolism showed no clear pattern. Although an increase in the receptor-mediated catabolism of low-density lipoprotein was demonstrated in five patients, no change or a slight decrease was seen in three patients. Production rates were not significantly altered, although there was a slight decrease in the median value (from 12.4 to 9.7 mg day−1 kg−1). Plasma lathosterol concentration was reduced in all eight patients (range 34–71%), indirectly confirming significant inhibition of cholesterol synthesis. 5. These results suggest that, as in patients with primary moderate hyperlipidaemia, the significant cholesterol-lowering effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in the nephrotic syndrome is accompanied by variable changes in lipoprotein metabolism. The reasons for this heterogeneous response are unclear. This reflects our limited understanding of the metabolic basis of nephrotic hyperlipidaemia and the relationship between hepatic sterol synthesis and plasma lipoprotein kinetics.

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