Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions.
Open accessAbstract
The atherogenicity theory for triglyceride-rich lipoproteins (TRLs; VLDL + intermediate density lipoprotein) generally cites the action of apolipoprotein C-III (apoC-III), a component of some TRLs, to retard their metabolism in plasma. We studied the kinetics of multiple TRL and LDL subfractions according to the content of apoC-III and apoE in 11 hypertriglyceridemic and normolipidemic persons. The liver secretes mainly two types of apoB lipoproteins: TRL with apoC-III and LDL without apoC-III. Approximately 45% of TRLs with apoC-III are secreted together with apoE. Contrary to expectation, TRLs with apoC-III but not apoE have fast catabolism, losing some or all of their apoC-III and becoming LDL. In contrast, apoE directs TRL flux toward rapid clearance, limiting LDL formation. Direct clearance of TRL with apoC-III is suppressed among particles also containing apoE. TRLs without apoC-III or apoE are a minor, slow-metabolizing precursor of LDL with little direct removal. Increased VLDL apoC-III levels are correlated with increased VLDL production rather than with slow particle turnover. Finally, hypertriglyceridemic subjects have significantly greater production of apoC-III-containing VLDL and global prolongation in residence time of all particle types. ApoE may be the key determinant of the metabolic fate of atherogenic apoC-III-containing TRLs in plasma, channeling them toward removal from the circulation and reducing the formation of LDLs, both those with apoC-III and the main type without apoC-III.
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In hypertriglyceridemia, more VLDL particles, as measured by apoB, and larger and more triglyceride- and apoC-III-enriched lipoproteins are found.
“In hypertriglyceridemia, more VLDL particles, as measured by apoB, and larger and more triglyceride-and apoC-III-enriched lipoproteins are found (39,64,65).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [64]
The Results report higher VLDL apoB and VLDL apoC-III concentrations in hypertriglyceridemic participants. The section on slow TRL metabolism also reports increased secretion of light VLDL, supporting a shift toward larger particles. However, the cited passages do not establish that individual lipoprotein particles are more triglyceride- and apoC-III-enriched in hypertriglyceridemia; the reported triglyceride content per particle compares particles with and without apoC-III across participants. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNearly all VLDL particles containing APOC-III undergo intravascular triglyceride lipolysis, generating LDL particles that also contain APOC-III.
“Studies have shown that nearly all VLDL particles containing APOC-III undergo intravascular triglyceride lipolysis, generating LDL particles that also contain APOC-III [25–27].”
From The Efficacy and Safety of Plozasiran on Lipid Profile in Dyslipidemic Disorders: A Systematic Review and Meta-Analysis (2026) · cites this paper as [26]
The Results section on TRLs with apoC-III but not apoE reports that lipolysis can produce LDL that retains apoC-III. But it reports that only 70% of those TRLs reach LDL, with just 20% producing apoC-III-containing LDL; the Results section on TRLs containing both apoE and apoC-III says only 10% reach LDL. The claim overstates both how many apoC-III-containing particles become LDL and how often the resulting LDL retains apoC-III. (LLM, conf=0.92)
Experimental — accuracy not yet measuredClearance of VLDL from the circulation is reduced in many patients with hypertriglyceridemia, in part due to saturation of triglyceride clearance.
“Clearance of VLDL from the circulation is reduced in many patients with hypertriglyceridemia (64, 65, 73), in part due to saturation of triglyceride clearance (74).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [64]
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- Authors
- Chunyu, Z., Christina, K., Katsunori, I., & Sacks, F. M.
- Affiliations
- Harvard University (US)
- Jikei University School of Medicine (JP)
- Corresponding author
- Sacks, Frank M.
- ORCID
- Sacks, Frank M.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 48
- Issue
- 5
- Pages
- 1190-1203
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2099054337
- Cited by
- 95
- References
- 51
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 11 · 2015: 8 · 2014: 6 · 2013: 3 · 2012: 4
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (5r01hl034980-07, RR‐02635)
- National Heart, Lung, and Blood Institute (R01HL56210, R01HL056210, RR-02635, R01HL-34980)
- National Center for Research Resources (RR02635, M01RR002635)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein C-III, triglyceride-rich lipoproteins, VLDL, intermediate density lipoprotein, LDL subfractions, apolipoprotein E, lipoprotein turnover, lipoprotein clearance, hypertriglyceridemia, atherogenic lipoproteins, VLDL production
- MeSH terms
- Apolipoproteins E, Female, Humans, Cholesterol, LDL, Liver, Male, Middle Aged, Time Factors, Triglycerides, Hypertriglyceridemia, Cholesterol, VLDL, Apolipoprotein C-III
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