Regulatory effects of the saturated fatty acids 6:0 through 18:0 on hepatic low density lipoprotein receptor activity in the hamster

Laura A. Woollett, David K. Spady, John M. Dietschy

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

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 (J(t)) found in animals or man. This study delineates which saturated fatty acids alter Jm and J(t) and so increase the plasma LDL-cholesterol level. Jm and J(t) were measured in vivo in hamsters fee 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 J(t), 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.

Original languageEnglish (US)
Pages (from-to)1133-1141
Number of pages9
JournalJournal of Clinical Investigation
Volume89
Issue number4
DOIs
StatePublished - 1992

Keywords

  • atherosclerosis
  • cholesterol esters
  • saturated fat

ASJC Scopus subject areas

  • Medicine(all)

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