Fatty acids regulate hepatic low density lipoprotein receptor activity through redistribution of intracellular cholesterol pools.
When the intake of dietary cholesterol in the hamster is constant, feeding the saturated 14:0 fatty acid (n-tetradecanoic acid) elevates the plasma low density lipoprotein (LDL) cholesterol concentration from 72 to 204 mg/dl, while the monounsaturated 18:1 fatty acid (cis-9-octadecenoic acid) lowers this level to 28 mg/dl. The 14:0 fatty acid lowers the hepatic cholesteryl ester concentration from 12 to 5 mg/g, while the abundance of this fatty acid in the ester fraction is increased 13-fold. Hepatic LDL receptor activity is depressed to 41% of control, while the LDL cholesterol production rate is increased to 132%. These changes account for the 3-fold increase in the plasma LDL cholesterol concentration. In contrast, feeding the 18:1 fatty acid increases hepatic cholesteryl ester concentration to 21 mg/g, and the abundance of this acid in the esters is increased 1.4-fold. Hepatic receptor activity is increased to 145%, while the production rate is suppressed to 68% of control. These changes account for the decrease in plasma LDL cholesterol level to 28 mg/dl. Despite these marked changes in LDL metabolism, however, the 14:0 and 18:1 fatty acids cause no change in net cholesterol balance across the liver. These results suggest that there are two fundamentally different mechanisms regulating hepatic LDL metabolism. One involves changes in net sterol balance across the liver brought about by alterations in the rate of cholesterol or bile acid absorption across the intestine, while the second is articulated through a redistribution of the putative sterol regulatory pool within the hepatocyte that is dictated by the type of long-chain fatty acid that reaches the liver.
Daumerie
C M
CM
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8887.
Woollett
L A
LA
Dietschy
J M
JM
D000818:Animals; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000378:metabolism*; D006224:Cricetinae; D004041:Dietary Fats / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D011973:Receptors, LDL / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis; D014280:Triglycerides / Q000378:metabolism
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D005227:Fatty Acids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D013261:Sterols; D014280:Triglycerides; D002784:Cholesterol