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Cited by 56Fatty Acid Research and HealthCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

Low density lipoprotein from humans supplemented with n-3 fatty acids depresses both LDL receptor activity and LDLr mRNA abundance in HepG2 cells.

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Lindsey, S, Pronczuk, A, Hayes, KC·1992·Journal of Lipid Research
DOI 10.1016/s0022-2275(20)41429-4
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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.

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Authors
Lindsey, S., Pronczuk, A., & Hayes, K.
Affiliations
Brandeis University (US)
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
1992-05
Volume
33
Issue
5
Pages
647-658
ISSN
0022-2275 (ISSN-L)
DOI
10.1016/s0022-2275(20)41429-4
OpenAlex
W2337906510
Cited by
56
References
57
Citations by year
2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 3
FWCI
4.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
fish oil supplementation, omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, LDL receptor, LDL receptor mRNA, LDL cholesterol, cholesterol esters, free cholesterol, HMG-CoA reductase, apolipoprotein A-I, LDL clearance, HepG2 cells, cholesterol metabolism
MeSH terms
Apolipoproteins, Cholesterol, Chromatography, Gas, Chromatography, High Pressure Liquid, Docosahexaenoic Acids, Female, Fish Oils, Humans, Hydroxymethylglutaryl CoA Reductases, Lipoproteins, HDL, Lipoproteins, LDL, Lipoproteins, VLDL, Male, Receptors, LDL, RNA, Messenger, Tumor Cells, Cultured, Vitamin E, Eicosapentaenoic Acid, Fatty Acids, Omega-3

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