Apolipoprotein C-III inhibition to lower triglycerides: one ring to rule them all?
Abstract
Metabolic choke points are shown at which apolipoprotein (apo) C-III—depicted in two-dimensional semi-circular form—probably affects triglyceride (TG)-rich lipoprotein metabolism. Circled plus (+) and minus (−) signs indicate metabolic steps that apo C-III either promotes or inhibits, respectively. Starting at the upper left (A), dietary fat from the intestine is packaged into chylomicrons (B), which include apo C-III on their surface; apo C-III may promote chylomicron secretion. On the right, TG of endogenous (i.e. hepatic) origin is packaged into very-low-density lipoprotein (VLDL), whose secretion is almost certainly promoted by apo C-III (E). In the plasma space, apo C-III inhibits: (i) lipoprotein lipase (LPL)—indicated in monomeric cartoon form—by impairing the hydrolysis of chylomicrons (C) into chylomicron remnants (D) and of VLDL (F) into intermediate-density lipoprotein (IDL) (G), which is ultimately remodelled into LDL; and (ii) hepatic uptake of TG-rich remnants (D). Interfering with apo C-III production reverses these effects, i.e. reduces secretion of TG-rich lipoproteins (E), increases hydrolysis of TG-rich lipoproteins by LPL (C and F) and permits hepatic removal of TG-rich remnants (D). Metabolic choke points are shown at which apolipoprotein (apo) C-III—depicted in two-dimensional semi-circular form—probably affects triglyceride (TG)-rich lipoprotein metabolism. Circled plus (+) and minus (−) signs indicate metabolic steps that apo C-III either promotes or inhibits, respectively. Starting at the upper left (A), dietary fat from the intestine is packaged into chylomicrons (B), which include apo C-III on their surface; apo C-III may promote chylomicron secretion. On the right, TG of endogenous (i.e. hepatic) origin is packaged into very-low-density lipoprotein (VLDL), whose secretion is almost certainly promoted by apo C-III (E). In the plasma space, apo C-III inhibits: (i) lipoprotein lipase (LPL)—indicated in monomeric cartoon form—by impairing the hydrolysis of chylomicrons (C) into chylomicron remnants (D) and of VLDL (F) into intermediate-density lipoprotein (IDL) (G), which is ultimately remodelled into LDL; and (ii) hepatic uptake of TG-rich remnants (D). Interfering with apo C-III production reverses these effects, i.e. reduces secretion of TG-rich lipoproteins (E), increases hydrolysis of TG-rich lipoproteins by LPL (C and F) and permits hepatic removal of TG-rich remnants (D).
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Elevated levels of apolipoprotein C-III lead to chylomicronemia and severe hypertriglyceridemia by inhibiting LPL activity, inhibiting hepatic uptake of triglyceride-rich lipoproteins, and increasing hepatic secretion of triglyceride-rich lipoproteins.
“In contrast, elevated levels of apolipoprotein C-III lead to chylomicronemia and severe hypertriglyceridemia by inhibiting LPL activity, 21 inhibiting hepatic uptake of triglyceride-rich lipoproteins, 22 and increasing hepatic secretion of triglyceride-rich lipoproteins. 21”
From Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome (2024) · cites this paper as [21]
Conventional triglyceride-lowering agents such as fibrates and omega-3 fatty acids have not been effective in lowering triglyceride levels in patients with familial chylomicronemia syndrome.
“and these agents have not been effective in lowering triglyceride levels in patients with familial chylomicronemia syndrome. 21,34”
From Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome (2024) · cites this paper as [21]
The reduction in apolipoprotein C-III levels by conventional triglyceride-lowering agents such as fibrates and omega-3 fatty acids is modest (10 to 40%).
“Moreover, the reduction in apolipoprotein C-III levels by the conventional triglyceride-lowering agents, such as fibrates and omega-3 fatty acids, is modest (10 to 40%)”
From Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome (2024) · cites this paper as [21]
Cites
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz962 · Cited by 1,601 · see citing works
Self-citationVolanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome
Witztum, J. L., Gaudet, D., Freedman, S. D., Alexander, V. J., Digenio, A., Williams, K. R., Yang, Q., Hughes, S. G., Geary, R. S., Arca, M., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1715944 · Cited by 669 · see citing works
Clinical review on triglycerides
Laufs, U., Parhofer, K. G., Ginsberg, H. N., & Hegele, R. A. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz785 · Cited by 544 · see citing works
Self-citationPradhan, A. D., Paynter, N. P., Everett, B. M., Glynn, R. J., Amarenco, P., Elam, M., Ginsberg, H., Hiatt, W. R., Ishibashi, S., Koenig, W., et al. (2018) · American Heart Journal · doi:10.1016/j.ahj.2018.09.011 · Cited by 319 · see citing works
Marston, N. A., Giugliano, R. P., Im, K., Silverman, M. G., O’Donoghue, M. L., Wiviott, S. D., Ference, B. A., & Sabatine, M. S. (2019) · Circulation · doi:10.1161/circulationaha.119.041998 · Cited by 301 · cited 6× · see citing works
“175 mg/dL); furthermore, 1:500 has TG. 10 mmol/L (.”
BackgroundInfluentialGenetics of hypertriglyceridemia
Dron, J. S., & Hegele, R. A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00455 · Cited by 244 · see citing works
Self-citationGouni-Berthold, I., Alexander, V. J., Yang, Q., Hurh, E., Steinhagen-Thiessen, E., Moriarty, P. M., Hughes, S. G., Gaudet, D., Hegele, R. A., O'Dea, L. S. L., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00046-2 · Cited by 232 · see citing works
Self-citationTardif, J.-C., Karwatowska-Prokopczuk, E., Amour, E. S., Ballantyne, C. M., Shapiro, M. D., Moriarty, P. M., Baum, S. J., Hurh, E., Bartlett, V. J., Kingsbury, J., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehab820 · Cited by 210 · see citing works
The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans
Borén, J., Packard, C. J., & Taskinen, M.-R. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00474 · Cited by 196 · see citing works
Boden, W. E., Bhatt, D. L., Toth, P. P., Ray, K. K., Chapman, M. J., & Lüscher, T. F. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz778 · Cited by 81 · see citing works
ApoCIII: A multifaceted protein in cardiometabolic disease
D’Erasmo, L., Costanzo, A. D., Gallo, A., Bruckert, É., & Arca, M. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154395 · Cited by 52 · see citing works
Hypertriglyceridemia: new approaches in management and treatment
Wolska, A. T., Yang, Z., & Remaley, A. T. (2020) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000710 · Cited by 50 · see citing works
Volanesorsen for treatment of familial chylomicronemia syndrome
Lazarte, J., & Hegele, R. A. (2021) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2021.1955348 · Cited by 25 · see citing works
Self-citation2019 George Lyman Duff Memorial Lecture
Hegele, R., & Dron, J. (2020) · Arteriosclerosis, Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.313065 · Cited by 14 · see citing works
Self-citationGanda, O. P. (2020) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000694 · Cited by 11 · see citing works
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Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome
Stroes, E. S. G., Alexander, V. J., Karwatowska-Prokopczuk, E., Hegele, R. A., Arca, M., Ballantyne, C. M., Soran, H., Prohaska, T. A., Xia, S., Ginsberg, H. N., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2400201 · Cited by 271 · see citing works
Self-citationKamrul-Hasan, A. B. M., Dutta, D., Nagendra, L., Mondal, S., Bhattacharya, S., & Kalra, S. (2024) · Endocrine Practice · doi:10.1016/j.eprac.2024.08.013 · Cited by 17 · see citing works
- Authors
- Hegele, R. A.
- Affiliations
- Western University (CA)
- Corresponding author
- Hegele, Robert A.
- ORCID
- Hegele, Robert A.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-02-17
- Volume
- 43
- Issue
- 14
- Pages
- 1413-1415
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W4206010204
- Cited by
- 29
- References
- 15
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 3 · 2022: 6
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Jacob J. Wolfe Distinguished Medical Research Chair
- the Edith Schulich Vinet Research Chair
- the Martha G. Blackburn Chair
- Canadian Institutes of Health Research
- Heart and Stroke Foundation of Ontario (G-21-0031455)
- Academic Medical Association of Southwestern Ontario (INN21-011)
- 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, triglyceride metabolism, lipoprotein lipase inhibition, chylomicrons, chylomicron remnants, hypertriglyceridemia, lipoprotein metabolism, hepatic lipase
- MeSH terms
- Humans, Triglycerides, Hypertriglyceridemia, Apolipoprotein C-III
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