Cited by 276Lipid metabolism and disordersLipoproteins and Cardiovascular HealthCholesterol and Lipid Metabolism

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ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors

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Gordts, Philip L.S.M., Nock, Ryan, Son, Ni-Huiping, Ramms, Bastian, Lew, Irene, Gonzales, Jon C., Thacker, Bryan E., Basu, Debapriya, Lee, Richard G., Mullick, Adam E., Graham, Mark J., Goldberg, Ira J., Crooke, Rosanne M., Witztum, Joseph L., Esko, Jeffrey D.·2016·Journal of Clinical Investigation

DOI 10.1172/jci86610PMC PMC4966320

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Abstract

Hypertriglyceridemia is an independent risk factor for cardiovascular disease, and plasma triglycerides (TGs) correlate strongly with plasma apolipoprotein C-III (ApoC-III) levels. Antisense oligonucleotides (ASOs) for ApoC-III reduce plasma TGs in primates and mice, but the underlying mechanism of action remains controversial. We determined that a murine-specific ApoC-III-targeting ASO reduces fasting TG levels through a mechanism that is dependent on low-density lipoprotein receptors (LDLRs) and LDLR-related protein 1 (LRP1). ApoC-III ASO treatment lowered plasma TGs in mice lacking lipoprotein lipase (LPL), hepatic heparan sulfate proteoglycan (HSPG) receptors, LDLR, or LRP1 and in animals with combined deletion of the genes encoding HSPG receptors and LDLRs or LRP1. However, the ApoC-III ASO did not lower TG levels in mice lacking both LDLR and LRP1. LDLR and LRP1 were also required for ApoC-III ASO-induced reduction of plasma TGs in mice fed a high-fat diet, in postprandial clearance studies, and when ApoC-III-rich or ApoC-III-depleted lipoproteins were injected into mice. ASO reduction of ApoC-III had no effect on VLDL secretion, heparin-induced TG reduction, or uptake of lipids into heart and skeletal muscle. Our data indicate that ApoC-III inhibits turnover of TG-rich lipoproteins primarily through a hepatic clearance mechanism mediated by the LDLR/LRP1 axis.

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Nordestgaard, B. G., & Varbo, A. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61177-6 · Cited by 1,419
Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management
Chapman, M. J., Ginsberg, H. N., Amarenco, P., Andreotti, F., Borén, J., Catapano, A. L., Descamps, O. S., Fisher, E., Kovanen, P. T., Kuivenhoven, J. A., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr112 · Cited by 1,227
Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
The TG and HDL Working Group of the Exome Sequencing Project, N. H. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1307095 · Cited by 1,071
Loss-of-Function Mutations in APOC3 and Risk of Ischemic Vascular Disease
Jørgensen, A. B., Frikke-Schmidt, R., Nordestgaard, B. G., & Tybjærg-Hansen, A. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1308027 · Cited by 919
A Null Mutation in Human APOC3 Confers a Favorable Plasma Lipid Profile and Apparent Cardioprotection
Pollin, T. I., Damcott, C. M., Shen, H., Ott, S. H., Shelton, J., Horenstein, R. B., Post, W., McLenithan, J. C., Bielak, L. F., Peyser, P. A., et al. (2008) · Science · doi:10.1126/science.1161524 · Cited by 688
The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management
Hegele, R. A., Ginsberg, H. N., Chapman, M. J., Nordestgaard, B. G., Kuivenhoven, J. A., Averna, M., Borén, J., Bruckert, E., Catapano, A. L., Descamps, O. S., et al. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70191-8 · Cited by 635
Hypertriglyceridemia as a Result of Human apo CII Gene Expression in Transgenic Mice
Ito, Y., Azrolan, N., O'Connell, A., Walsh, A., & Breslow, J. L. (1990) · Science · doi:10.1126/science.2167514 · Cited by 539
Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia
Gaudet, D., Alexander, V. J., Baker, B. F., Brisson, D., Tremblay, K., Singleton, W., Geary, R. S., Hughes, S. G., Viney, N. J., Graham, M. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1400283 · Cited by 528
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Inhibition of lipoprotein lipase by an apoprotein of human very low density lipoprotein
Brown, W. V., & Baginsky, M. L. (1972) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(72)80149-9 · Cited by 493
Targeting APOC3 in the familial chylomicronemia syndrome
Gaudet, D., Brisson, D., Tremblay, K., Alexander, V. J., Singleton, W., Hughes, S. G., Geary, R. S., Baker, B. F., Graham, M. J., Crooke, R. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400284 · Cited by 491
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“It also delays clearance of triglyceride-rich lipoproteins by hepatocytes [12].”
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“It also has a negative effect on TRL clearance through the reduction of their uptake by members of the LDL receptor family in the liver, an LPL-independent pathway [88].”
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Rodia, C. N., Li, D., Tambini, N. S., Johnson, Z. K., Jellison, E. R., Vella, A. T., & Kohan, A. B. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/823690 · Cited by 3
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Yamauchi, J., Kim, D. H., & Dong, H. H. (2017) · Springer eBooks · doi:10.1007/978-3-319-67199-4_634 · Cited by 3
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Alterman, J. F., Gross, K. Y., & Khvorova, A. (2026) · Nucleic Acid Therapeutics · doi:10.1177/21593337261435980 · Cited by 2
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Goldberg, I. J., Young, M. E., Schulze, P. C., & Drosatos, K. (2026) · Circulation Research · doi:10.1161/circresaha.126.327471 · Cited by 3
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Saum, K. L., Pennathur, S., & Kanter, J. E. (2026) · Circulation Research · doi:10.1161/circresaha.126.327361 · Cited by 3
Human apolipoprotein CIII levels; evaluation of three assay methods
Sandin, Å., Olofsson, C., Strålfors, A., Ekberg, N. R., Brismar, K., Juntti‐Berggren, L., & Eggertsen, G. (2020) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2020.1725976 · Cited by 2
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Okajima, F., Kurihara, O., & Takano, M. (2019) · Aging · doi:10.18632/aging.101969 · Cited by 2
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Chen, Z., Triatin, R. D., Luo, L., Snieder, H., Schmidt, A. F., Ditmarsch, M., Kastelein, J. J. P., Dullaart, R. P. F., Kuivenhoven, J. A., & Thio, C. H. L. (2026) · Cardiovascular Diabetology · doi:10.1186/s12933-026-03209-w · Cited by 1
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Wu, M. J., Yang, C., Wu, S., Devlin, G. W., Lin, F., Asokan, A., & Neher, S. B. (2026) · Disease Models & Mechanisms · doi:10.1242/dmm.052897 · Cited by 1
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Khan, I., Meenakshi, S., Abubakar, M., Kumar, N., Gaikwad, V. L., Rai, A., & Murti, K. (2026) · Endocrine · doi:10.1007/s12020-026-04686-5 · Cited by 1
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Dedousis, N. L., Teng, L., & Kohan, A. B. (2022) · Journal of Visualized Experiments · doi:10.3791/64338 · Cited by 2
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Ueda, M. (2024) · Translational Pediatrics · doi:10.21037/tp-24-131 · Cited by 2
“Beside the process described above, several diagnostic algorithms of FCS have been published (79-81).”
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Liu, Y., Ko, J., Skudder‐Hill, L., Shamaitijiang, X., Sequeira, I. R., & Petrov, M. S. (2025) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2025.104280 · Cited by 1
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Titov, V. N., Ta, R., Ивановна, К. В., & Alchinova, I. B. (2019) · Russian Clinical Laboratory Diagnostics · doi:10.18821/0869-2084-2019-64-1-4-13 · Cited by 1
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Colaco, I. B., Araújo, F., Aguiar, P., Cruz, D., Bourbon, M., Duarte, J. S., & Veríssimo, M. T. (2021) · Medicina Interna · doi:10.24950/rspmi.r.92.4.2021 · Cited by 1
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Vitali, C., Stankov, S. G., Khetarpal, S. A., Millar, J. S., Mayne, L. C., Englander, S. W., Hand, N. J., Lund‐Katz, S., Phillips, M. C., & Rader, D. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.02.183178 · Cited by 1
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Rodríguez, M. M., Rehues, P., Iranzo, V., Mora, J. D., Balsells, C., Guardiola, M., & Ribalta, J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.15.298802 · Cited by 1
“Our results show that Apo CIII0b and Apo CIII1d proteoforms are negatively associated with TG and TRL levels in healthy young men and remained associated after adjusting for total Apo C-III concentrations.”
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Ljunggren, S. (2016) · Linköping University medical dissertations · doi:10.3384/diss.diva-131643
“Another protein preferentially located in HDL2 is apoC-III, which is an 11 kDa protein that acts as an inhibitor of lipoprotein lipase, and also interferes with lipoprotein binding to hepatic receptors [Gordts et al. 2016].”
Background
Key Differences Between Hepatic and Intestinal apoC3 Regulation and Expression, and Implications for Cardiovascular Disease Risk
West, G. (2017) · OpenCommons - UConn (University of Connecticut)
Pathways for kidney triglyceride accumulation
Scerbo, D. A. (2017) · doi:10.7916/d8wh32kv
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Kovrov, O. (2019) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Lipoproteins in the postprandial state: Studies on the metabolism of triglyceride-rich lipoproteins using multicompartmental models
Björnson, E. (2021) · Gothenburg University Publications Electronic Archive (Gothenburg University)
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Wang, Y. E., Kirschke, C. P., Woodhouse, L. R., Bonnel, E. L., Stephensen, C. B., Bennett, B. J., Newman, J. W. I., Keim, N. L., & Huang, L. (2020) · doi:10.21203/rs.3.rs-94525/v1
“APOC3 can significantly reduce the clearance rate of APOB-containing lipoprotein particles by inhibiting the receptor-mediated endocytosis [14].”
Background
SNPs in Apolipoproteins Contribute to Sex-dependent Differences in Blood Lipids Before and After a High-fat Dietary Challenge in Healthy U.S. AdultsPreprint
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Bobik, A., Cohen, N. D., Jenkins, A. J., Kyaw, T. S., SULLIVAN, D. R., Wu, X., Yu, X.-Y., & Little, P. J. (2023) · Contemporary diabetes · doi:10.1007/978-3-031-26681-2_30
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Additional file 1 of Apolipoprotein C3 is negatively associated with estrogen and mediates the protective effect of estrogen on hypertriglyceridemia in obese adults
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Additional file 2 of Apolipoprotein C3 is negatively associated with estrogen and mediates the protective effect of estrogen on hypertriglyceridemia in obese adults
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Cariño‐Cortés, R., Manuel, M.-P. V., Ortiz, M. I., Luis, J.-S., Fernández‐Martínez, E., & Fernanda, V.-C. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-27370-4.00005-6
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Additional file 3 of SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults
Wang, Y. E., Kirschke, C. P., Woodhouse, L. R., Bonnel, E. L., Stephensen, C. B., Bennett, B. J., Newman, J. W., Keim, N. L., & Huang, L. (2022) · Figshare · doi:10.6084/m9.figshare.20782248
Additional file 2 of SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults
Wang, Y. E., Kirschke, C. P., Woodhouse, L. R., Bonnel, E. L., Stephensen, C. B., Bennett, B. J., Newman, J. W., Keim, N. L., & Huang, L. (2022) · Figshare · doi:10.6084/m9.figshare.20782245
Additional file 4 of SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults
Wang, Y. E., Kirschke, C. P., Woodhouse, L. R., Bonnel, E. L., Stephensen, C. B., Bennett, B. J., Newman, J. W., Keim, N. L., & Huang, L. (2022) · Figshare · doi:10.6084/m9.figshare.20782251
Additional file 1 of SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults
Wang, Y. E., Kirschke, C. P., Woodhouse, L. R., Bonnel, E. L., Stephensen, C. B., Bennett, B. J., Newman, J. W., Keim, N. L., & Huang, L. (2022) · Figshare · doi:10.6084/m9.figshare.20782242
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Self-citation
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“Among these, apoC-II and apoC-III, both primarily synthesized in the liver, play opposing roles: apoC-II activates LPL, whereas apoC-III inhibits LPL activity and delays the clearance of triglyceride-rich lipoproteins (Gordts et al., 2016; Kinnunen et al., 1977; Taskinen et al., 2022).”
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“It inhibits LPL-mediated TRL lipolysis and reduces hepatic uptake of TRL remnant particles, thereby impairing TRL clearance [ 427 ].”
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Authors: Gordts, P. L. S. M., Nock, R., Son, N.-H., Ramms, B., Lew, I., Gonzales, J. C., Thacker, B. E., Basu, D., Lee, R. G., Mullick, A. E., Graham, M. J., Goldberg, I. J., Crooke, R. M., Witztum, J. L., & Esko, J. D.
Affiliations: University of California San Diego (US)
NYU Langone Health (US)
Bielefeld University (DE)
Ionis Pharmaceuticals (United States) (US)
Corresponding author: Gordts, Philip L.S.M.
Esko, Jeffrey D.
ORCID: Gordts, Philip L.S.M.
Son, Ni-Huiping
Ramms, Bastian
Lew, Irene
Thacker, Bryan E.
Basu, Debapriya
Lee, Richard G.
Mullick, Adam E.
Goldberg, Ira J.
Witztum, Joseph L.
Esko, Jeffrey D.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2016-07-11
Volume: 126
Issue: 8
Pages: 2855-2866
ISSN: 0021-9738 (ISSN-L)
1558-8238
DOI: 10.1172/jci86610
PMC: PMC4966320
OpenAlex: W2471143596
Cited by: 274
References: 47
Citations by year: 2026: 32 · 2025: 20 · 2024: 24 · 2023: 19 · 2022: 27 · 2021: 35 · 2020: 35 · 2019: 30 · 2018: 21 · 2017: 22 · 2016: 8
FWCI: 22.27
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health
National Heart, Lung, and Blood Institute (R01HL045095, P01HL092969, P01HL107150, R37HL045095, P01HL088093)
National Institute of General Medical Sciences (R01GM033063, R37GM033063)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords: apolipoprotein C-III, antisense oligonucleotides, triglyceride-rich lipoproteins, LDL receptor, hypertriglyceridemia, heparan sulfate proteoglycans, lipoprotein lipase, high-fat diet, cardiovascular risk
MeSH terms: Animals, Female, Genotype, Heparin, Ketones, Lipoproteins, Liver, Male, Mice, Inbred C57BL, Mice, Transgenic, Myocardium, Receptors, LDL, Risk Factors, Triglycerides, Hepatocytes, Tumor Suppressor Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Mice, Apolipoprotein C-III

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ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors

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