Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.
The concentration of LDL in plasma is strongly influenced by the amount and the type of lipid in the diet. Recent studies in the hamster have shown that dietary fatty acids differentially affect circulating LDL levels primarily by altering receptor-dependent LDL uptake in the liver. To investigate the mechanistic basis of this effect, rates of receptor-dependent LDL transport in the liver were correlated with LDL receptor protein and mRNA levels in hamsters fed safflower oil or coconut oil and varying amounts of cholesterol. Hepatic LDL receptor activity was significantly lower in animals fed coconut oil than in animals fed safflower oil at all levels of cholesterol intake (26, 53, and 61% lower at cholesterol intakes of 0, 0.06, and 0.12%, respectively). These fatty acid-induced changes in hepatic LDL receptor activity were accompanied by parallel changes in hepatic LDL receptor protein and mRNA levels, suggesting that dietary fatty acids regulate the LDL receptor pathway largely at the mRNA level.
Horton
J D
JD
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Cuthbert
J A
JA
Spady
D K
DK
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000097:blood; D000074263:Coconut Oil; D006224:Cricetinae; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010938:Plant Oils / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D011973:Receptors, LDL / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012450:Safflower Oil / Q000494:pharmacology
D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D004041:Dietary Fats; D005227:Fatty Acids; D008077:Lipoproteins, LDL; D009838:Oligodeoxyribonucleotides; D010938:Plant Oils; D012333:RNA, Messenger; D011973:Receptors, LDL; D012450:Safflower Oil; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D000074263:Coconut Oil