Cited by 133Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthLipid metabolism and disorders

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Elevated Triglyceride Content Diminishes the Capacity of High Density Lipoprotein to Deliver Cholesteryl Esters via the Scavenger Receptor Class B Type I (SR-BI)

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Greene, Diane J., Skeggs, Josephine W., Morton, Richard E.·2001·Journal of Biological Chemistry

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Abstract

The selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE) by the scavenger receptor class B type I (SR-BI) is well documented. However, the effect of altered HDL composition, such as occurs in hyperlipidemia, on this important process is not known. This study investigated the impact of variable CE and triglyceride (TG) content on selective uptake. CE selective uptake by Y1 and HepG2 cells was strongly affected by modification of either the CE or TG content of HDL. Importantly, TG, like CE, was selectively taken up by a dose-dependent, saturable process in these cells. As shown by ACTH up-regulation and receptor overexpression experiments, SR-BI mediated the selective uptake of both CE and TG. With in vitro modified HDLs of varying CE and TG composition, the selective uptake of CE and TG was dependent on the abundance of each lipid within the HDL particle. Furthermore, total selective uptake (CE + TG) remained constant, indicating that these lipids competed for cellular uptake. These data support a novel mechanism whereby SR-BI binds HDL and mediates the incorporation of a nonspecific portion of the HDL lipid core. In this way, TG directly affects the ability of HDL to donate CE to cells. Processes that raise the TG/CE ratio of HDL will impair the delivery of CE to cells via this receptor and may compromise the efficiency of sterol balancing pathways such as reverse cholesterol transport.

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“Consistent with these findings, HDL capacity to deliver CE to hepatic cells through interaction with SR-BI diminishes as a result of HDL enrichment in TG (Greene et al., 2001).”
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Authors: Greene, D. J., Skeggs, J. W., & Morton, R. E.
Affiliations: Cleveland Clinic (US)
Corresponding author: Morton, Richard E.
ORCID: Morton, Richard E.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2001-02
Volume: 276
Issue: 7
Pages: 4804-4811
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m008725200
OpenAlex: W2053088392
Cited by: 133
References: 52
Citations by year: 2025: 3 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 12 · 2012: 8
FWCI: 7.54
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7191 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL060934, HL60934)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: high-density lipoprotein, scavenger receptor class B type I, cholesteryl ester uptake, triglyceride content, HDL lipid composition, selective uptake, reverse cholesterol transport, sterol balance, hyperlipidemia, receptor overexpression
MeSH terms: Animals, Biological Transport, Cell Line, Cholesterol Esters, Humans, Lipoproteins, HDL, Membrane Proteins, Receptors, Immunologic, Substrate Specificity, Transfection, Triglycerides, Receptors, Lipoprotein, CD36 Antigens, COS Cells, Receptors, Scavenger, Scavenger Receptors, Class B

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Elevated Triglyceride Content Diminishes the Capacity of High Density Lipoprotein to Deliver Cholesteryl Esters via the Scavenger Receptor Class B Type I (SR-BI)

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