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Low density lipoprotein from humans supplemented with n-3 fatty acids depresses both LDL receptor activity and LDLr mRNA abundance in HepG2 cells.
J Lipid Res. 1992 May; 33(5):647-58.JL

Abstract

Fish oil supplementation in humans is often associated with an expanded low density lipoprotein (LDL) pool that is not thought to reflect increased production. Since data on clearance of LDL after fish oil supplementation (FO-LDL) are equivocal, normal volunteers (four men and three women) received ten capsules containing 3.6 g eicosapentaenoic acid and 2.9 g docosahexaenoic acid (approximately 2.5% total calories as methyl esters) for 2 weeks. Total plasma cholesterol was unchanged, but triglycerides decreased 30%. Low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were unchanged. Analysis of the LDL particles revealed that increased esterified cholesterol caused the FO-LDL core/surface ratio to be greater than baseline LDL (BL-LDL), resulting in a shift in mean LDL density from 1.060 to 1.056. N-3 fatty acids in FO-LDL were also increased greater than 40% at the expense of n-6 and n-9 fatty acids. Human hepatoma HepG2 cells were used to study the effects of FO-LDL on LDL receptor activity and mRNA abundance for the LDL receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and various apolipoproteins associated with cholesterol metabolism. In this system FO-LDL reduced LDL receptor activity compared to BL-LDL. Scatchard analysis revealed that LDL receptor number (Bmax) was reduced to one-third normal (P less than 0.001) whereas particle binding affinity was unchanged. The mRNA abundance for the LDL receptor and apoA-I were also depressed, even by low concentrations (10 micrograms/ml and 20 micrograms/ml LDL protein) of FO-LDL as compared to BL-LDL. HepG2 cells incubated with FO-LDL had decreased cellular free cholesterol but increased cholesteryl esters. Thus, moderate supplementation with fish oil n-3 fatty acids in normal humans enriches their LDL particles in cholesteryl esters and n-3 fatty acids. These particles depress both LDL receptor activity and LDL receptor mRNA abundance in HepG2 cells.

Authors+Show Affiliations

Foster Biomedical Research Laboratory, Brandeis University, Waltham, MA 02254.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1535648

Citation

Lindsey, S, et al. "Low Density Lipoprotein From Humans Supplemented With N-3 Fatty Acids Depresses Both LDL Receptor Activity and LDLr mRNA Abundance in HepG2 Cells." Journal of Lipid Research, vol. 33, no. 5, 1992, pp. 647-58.
Lindsey S, Pronczuk A, Hayes KC. Low density lipoprotein from humans supplemented with n-3 fatty acids depresses both LDL receptor activity and LDLr mRNA abundance in HepG2 cells. J Lipid Res. 1992;33(5):647-58.
Lindsey, S., Pronczuk, A., & Hayes, K. C. (1992). Low density lipoprotein from humans supplemented with n-3 fatty acids depresses both LDL receptor activity and LDLr mRNA abundance in HepG2 cells. Journal of Lipid Research, 33(5), 647-58.
Lindsey S, Pronczuk A, Hayes KC. Low Density Lipoprotein From Humans Supplemented With N-3 Fatty Acids Depresses Both LDL Receptor Activity and LDLr mRNA Abundance in HepG2 Cells. J Lipid Res. 1992;33(5):647-58. PubMed PMID: 1535648.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low density lipoprotein from humans supplemented with n-3 fatty acids depresses both LDL receptor activity and LDLr mRNA abundance in HepG2 cells. AU - Lindsey,S, AU - Pronczuk,A, AU - Hayes,K C, PY - 1992/5/1/pubmed PY - 1992/5/1/medline PY - 1992/5/1/entrez SP - 647 EP - 58 JF - Journal of lipid research JO - J Lipid Res VL - 33 IS - 5 N2 - Fish oil supplementation in humans is often associated with an expanded low density lipoprotein (LDL) pool that is not thought to reflect increased production. Since data on clearance of LDL after fish oil supplementation (FO-LDL) are equivocal, normal volunteers (four men and three women) received ten capsules containing 3.6 g eicosapentaenoic acid and 2.9 g docosahexaenoic acid (approximately 2.5% total calories as methyl esters) for 2 weeks. Total plasma cholesterol was unchanged, but triglycerides decreased 30%. Low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were unchanged. Analysis of the LDL particles revealed that increased esterified cholesterol caused the FO-LDL core/surface ratio to be greater than baseline LDL (BL-LDL), resulting in a shift in mean LDL density from 1.060 to 1.056. N-3 fatty acids in FO-LDL were also increased greater than 40% at the expense of n-6 and n-9 fatty acids. Human hepatoma HepG2 cells were used to study the effects of FO-LDL on LDL receptor activity and mRNA abundance for the LDL receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and various apolipoproteins associated with cholesterol metabolism. In this system FO-LDL reduced LDL receptor activity compared to BL-LDL. Scatchard analysis revealed that LDL receptor number (Bmax) was reduced to one-third normal (P less than 0.001) whereas particle binding affinity was unchanged. The mRNA abundance for the LDL receptor and apoA-I were also depressed, even by low concentrations (10 micrograms/ml and 20 micrograms/ml LDL protein) of FO-LDL as compared to BL-LDL. HepG2 cells incubated with FO-LDL had decreased cellular free cholesterol but increased cholesteryl esters. Thus, moderate supplementation with fish oil n-3 fatty acids in normal humans enriches their LDL particles in cholesteryl esters and n-3 fatty acids. These particles depress both LDL receptor activity and LDL receptor mRNA abundance in HepG2 cells. SN - 0022-2275 UR - https://www.unboundmedicine.com/medline/citation/1535648/Low_density_lipoprotein_from_humans_supplemented_with_n_3_fatty_acids_depresses_both_LDL_receptor_activity_and_LDLr_mRNA_abundance_in_HepG2_cells_ L2 - http://www.jlr.org/cgi/pmidlookup?view=long&pmid=1535648 DB - PRIME DP - Unbound Medicine ER -