Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice

Chandna Vasandani, Abdallah I. Kafrouni, Antonella Caronna, Yuriy Bashmakov, Michael Gotthardt, Jay D. Horton, David K. Spady

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

We determined the effects of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on parameters of plasma lipoprotein and hepatic lipid metabolism in LDL receptor (LDLr) knockout mice. Dietary n-3 PUFA decreased the rate of appearance and increased the hepatic clearance of IDL/LDL resulting in a marked decrease in the plasma concentration of these particles. Dietary n-3 PUFA increased the hepatic clearance of IDL/LDL through a mechanism that appears to involve apolipoprotein (apo)E but is independent of the LDLr, the LDLr related protein (LRP), the scavenger receptor B1, and the VLDLr. The decreased rate of appearance of IDL/VLDL in the plasma of animals fed n-3 PUFA could be attributed to a marked decrease in the plasma concentration of precursor VLDL. Decreased plasma VLDL concentrations were due in part to decreased hepatic secretion of VLDL triglyceride and cholesteryl esters, which in turn was associated with decreased concentrations of these lipids in liver. Decreased hepatic triglyceride concentrations in animals fed n-3 PUFA were due in part to suppression of fatty acid synthesis as a result of a decrease in sterol regulatory element binding protein-1 (SREBP-1) expression and processing. In conclusion, these studies indicate that n-3 PUFA can markedly decrease the plasma concentration of apoB-containing lipoproteins and enhance hepatic LDL clearance through a mechanism that does not involve the LDLr pathway or LRP.

Original languageEnglish (US)
Pages (from-to)772-784
Number of pages13
JournalJournal of lipid research
Volume43
Issue number5
StatePublished - May 18 2002

Keywords

  • Cholesterol
  • Fish oil
  • Lipoproteins
  • Liver
  • Polyunsaturated fatty acids
  • Triglyceride
  • VLDL

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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    Vasandani, C., Kafrouni, A. I., Caronna, A., Bashmakov, Y., Gotthardt, M., Horton, J. D., & Spady, D. K. (2002). Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice. Journal of lipid research, 43(5), 772-784.