Trans-9-octadecenoic acid is biologically neutral and does not regulate the low density lipoprotein receptor as the cis isomer does in the hamster.
The concentration of cholesterol carried in low density lipoproteins (LDL-C) is primarily determined by the rate at which LDL-C is produced (Jt) and the rate at which the liver takes up this particle through receptor-dependent transport (Jm). The accumulation of specific dietary fatty acids in the liver profoundly alters these kinetic parameters and will either increase hepatic receptor activity or further suppress Jm, depending upon the particular fatty acid that enriches the various lipid pools. This study tests the thesis that the cellular effects of each fatty acid are determined by the ability of that lipid to act as an effective substrate for cholesteryl ester formation by examining the metabolic effects of either cis-9-octadecenoic acid (18:1(9c)), the preferred substrate for esterification, or trans-9-octadecenoic acid (18:1(9t)), a poor substrate for this reaction. When fed to hamsters for 30 days, the steady-state concentration of cholesteryl esters was markedly increased by the 18:1(9c), as compared to the 18:1(9t), compound. In animals receiving the 18:1(9c) fatty acid, hepatic receptor activity was significantly increased, LDL-C production was suppressed, and the steady-state LDL-C concentration was reduced. In contrast, the 18:1(9t) fatty acid did not significantly alter Jm, Jt, or the plasma LDL-C level from those values found in the control animals fed an isocaloric amount of a biologically neutral fatty acid, octanoic acid. Despite these different effects on the parameters of LDL metabolism, neither the cis nor trans fatty acid altered net cholesterol delivery to the liver from de novo sterol synthesis in any tissue in the body or from uptake of dietary cholesterol across the intestine. Therefore, these studies provide strong support for the thesis that fatty acids exert regulatory effects on hepatic LDL receptor activity by altering the distribution of cholesterol in the hepatocyte between a putative regulatory pool and the inert pool of cholesteryl esters. The direction and magnitude of the effects of specific fatty acids on receptor-dependent LDL transport appear to relate directly to the capacity of specific fatty acids to either promote or inhibit cholesteryl ester formation.
Woollett
L A
LA
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8887.
Daumerie
C M
CM
Dietschy
J M
JM
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D006224:Cricetinae; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008954:Models, Biological; D019301:Oleic Acid; D009829:Oleic Acids / Q000737:chemistry / Q000494:pharmacology*; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013261:Sterols / Q000378:metabolism; D013329:Structure-Activity Relationship
D008078:Cholesterol, LDL; D004041:Dietary Fats; D009829:Oleic Acids; D011973:Receptors, LDL; D013261:Sterols; D019301:Oleic Acid; D002784:Cholesterol