Regulatory effects of the saturated fatty acids 6:0 through 18:0 on hepatic low density lipoprotein receptor activity in the hamster.
The plasma concentration of cholesterol carried in low density lipoproteins is principally determined by the level of LDL receptor activity (Jm) and the LDL-cholesterol production rate (Jt) found in animals or man. This study delineates which saturated fatty acids alter Jm and Jt and so increase the plasma LDL-cholesterol level. Jm and Jt were measured in vivo in hamsters fed a constant level of added dietary cholesterol (0.12%) and triacylglycerol (10%), where the triacylglycerol contained only a single saturated fatty acid varying in chain length from 6 to 18 carbon atoms. After feeding for 30 d, the 12:0, 14:0, 16:0, and 18:0 fatty acids, but not the 6:0, 8:0, and 10:0 compounds, became significantly enriched in the liver total lipid fraction of the respective groups fed these fatty acids. However, only the 12:0, 14:0, and 16:0 fatty acids, but not the 6:0, 8:0, 10:0, and 18:0 compounds, suppressed Jm, increased Jt, and essentially doubled plasma LDL-cholesterol concentrations. Neither the 16:0 nor 18:0 compound altered rates of cholesterol synthesis in the extrahepatic organs, and both lowered the hepatic total cholesterol pool. Thus, the different effects of the 16:0 and 18:0 fatty acids could not be attributed to a difference in cholesterol delivery to the liver. Since these changes in LDL kinetics took place without an apparent alteration in external sterol balance, the regulatory effects of the 12:0, 14:0, and 16:0 fatty acids presumably are mediated through some change in a putative intrahepatic regulatory pool of sterol in the liver.
Woollett
L A
LA
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Spady
D K
DK
Dietschy
J M
JM
D000818:Animals; D008078:Cholesterol, LDL / Q000378:metabolism; D006224:Cricetinae; D005227:Fatty Acids / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D011973:Receptors, LDL / Q000032:analysis*; D014280:Triglycerides / Q000494:pharmacology
D008078:Cholesterol, LDL; D005227:Fatty Acids; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides