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 Citations (Scopus)

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 - 2002

Fingerprint

LDL Receptors
Omega-3 Fatty Acids
Knockout Mice
Up-Regulation
Plasmas
Liver
Lipoproteins
Animals
Low Density Lipoprotein Receptor-Related Protein-1
Sterol Regulatory Element Binding Protein 1
Scavenger Receptors
Cholesterol Esters
Apolipoproteins B
Apolipoproteins E
oxidized low density lipoprotein
Lipid Metabolism
Triglycerides
Fatty Acids
Lipids
Processing

Keywords

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

ASJC Scopus subject areas

  • Endocrinology

Cite this

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.

Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice. / Vasandani, Chandna; Kafrouni, Abdallah I.; Caronna, Antonella; Bashmakov, Yuriy; Gotthardt, Michael; Horton, Jay D.; Spady, David K.

In: Journal of Lipid Research, Vol. 43, No. 5, 2002, p. 772-784.

Research output: Contribution to journalArticle

Vasandani, C, Kafrouni, AI, Caronna, A, Bashmakov, Y, Gotthardt, M, Horton, JD & Spady, DK 2002, 'Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice', Journal of Lipid Research, vol. 43, no. 5, pp. 772-784.
Vasandani C, Kafrouni AI, Caronna A, Bashmakov Y, Gotthardt M, Horton JD et al. Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice. Journal of Lipid Research. 2002;43(5):772-784.
Vasandani, Chandna ; Kafrouni, Abdallah I. ; Caronna, Antonella ; Bashmakov, Yuriy ; Gotthardt, Michael ; Horton, Jay D. ; Spady, David K. / Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice. In: Journal of Lipid Research. 2002 ; Vol. 43, No. 5. pp. 772-784.
@article{f0f40141a0884b6da9db0550d8afc83a,
title = "Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice",
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.",
keywords = "Cholesterol, Fish oil, Lipoproteins, Liver, Polyunsaturated fatty acids, Triglyceride, VLDL",
author = "Chandna Vasandani and Kafrouni, {Abdallah I.} and Antonella Caronna and Yuriy Bashmakov and Michael Gotthardt and Horton, {Jay D.} and Spady, {David K.}",
year = "2002",
language = "English (US)",
volume = "43",
pages = "772--784",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "5",

}

TY - JOUR

T1 - Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice

AU - Vasandani, Chandna

AU - Kafrouni, Abdallah I.

AU - Caronna, Antonella

AU - Bashmakov, Yuriy

AU - Gotthardt, Michael

AU - Horton, Jay D.

AU - Spady, David K.

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Cholesterol

KW - Fish oil

KW - Lipoproteins

KW - Liver

KW - Polyunsaturated fatty acids

KW - Triglyceride

KW - VLDL

UR - http://www.scopus.com/inward/record.url?scp=0036244839&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036244839&partnerID=8YFLogxK

M3 - Article

C2 - 11971949

AN - SCOPUS:0036244839

VL - 43

SP - 772

EP - 784

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 5

ER -