Cited by 339Lipid metabolism and disordersCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

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Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia.

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Mann, C J, Yen, F T, Grant, A M, Bihain, B E·1991·Journal of Clinical Investigation

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Abstract

Plasma net cholesteryl ester (CE) transfer and optimum cho- lesteryl ester transfer protein (CETP) activity were determined in primary hypertriglyceridemic (a = 11) and normolipidemic (a = 15) individuals.The hypertriglyceridemic group demon- strated threefold greater net CE transfer leading to enhanced accumulation of CE in VLDL.This increased net transfer was not accompanied by a change in CETP activity.In normolipide- mia, but not in hypertriglyceridemia, net CE transfer correlated with VLDL triglyceride (r = 0.92, P < 0.001).In contrast, net CE transfer in hypertriglyceridemia, but not in normolipide- mia, correlated with CETP activity (r = 0.73, P < 0.01).Correc- tion of hypertriglyceridemia with bezafibrate reduced net CE transfer towards normal and restored the correlation with VLDL triglyceride (r = 0.90, P < 0.005) while suppressing the correlation with CETP activity.That net CE transfer depends on VLDL concentration was confirmed by an increase ofnet CE transfer in normolipidemic plasma supplemented with purified VLDL.Supplementation of purified CETP to normolipidemic plasma did not stimulate net CE transfer.In contrast, net CE transfer was enhanced by addition of CETP to both plasma supplemented with VLDL and hypertriglyceridemic plasma.Thus, in normal subjects, VLDL concentration determines the rate of net CE transfer.CETP becomes rate limiting as VLDL concentration increases, i.e, in hypertriglyceridemia. (J.Clin.Invest.1991.88:2059-2066.)Key words: cholesteryl ester transfer protein * very low density lipoprotein -high density lipoprotein -cardiovascular disease * reverse cholesterol trans- port MO.Bezafibrate (2-[4-[2-[(4-chlorobenzoyl)amino]-ethyl]phenoxy]-2methylpropanoic acid) was obtained from Boehringer Mannheim (for- merly MCP Pharmaceuticals), Livingstone, Scotland. Cholesteryl Ester Transfer in Hypertriglyceridemia 2059

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Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment
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Background
Plasma lipoproteins from patients with poorly controlled diabetes mellitus and "in vitro" glycation of lipoproteins enhance the transfer rate of cholesteryl ester from HDL to apo-B-containing lipoproteins
Passarelli, M., Catanozi, S., Nakandakare, E. R., Rocha, J. C., Morton, R. E., Shimabukuro, A. F. M., & Quintão, E. C. R. (1997) · Diabetologia · doi:10.1007/s001250050791 · Cited by 52
Cholesteryl Ester Transfer Protein in Metabolic Syndrome
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Postprandial hyperglycemia and hyperlipidemia-generated glycoxidative stress: its contribution to the pathogenesis of diabetes complications.
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“It seems that regulation of CETP activity depends on TG levels, with a positive relationship with net CE transfer evident only in the presence of high TG [39].”
Background
Increased plasma cholesteryl ester transfer activity in obese children
Hayashibe, H., Asayama, K., Nakane, T., Uchida, N., Kawada, Y., & Nakazawa, S. (1997) · Atherosclerosis · doi:10.1016/s0021-9150(96)06014-5 · Cited by 48
“The reciprocal decrease in HDL-C occasionally found in the presence of hypertriglyceridemia may be due to an enhanced lipid transfer reaction [28].”
Background
Increased Serum Cholesteryl Ester Transfer Protein in Obese Children
Asayama, K., Hayashibe, H., Dobashi, K., Uchida, N., Nakane, T., Kodera, K., & Shirahata, A. (2002) · Obesity Research · doi:10.1038/oby.2002.61 · Cited by 48
“In hypertriglyceridemia, excessive TG changes the structure of TG-rich lipoproteins and then retards cholesterol transfer from HDL, leading to a compensatory increase in CETP and the reciprocal decrease in HDLC (”
Background
Plasma lipoprotein abnormalities in type 1 (insulin-dependent) diabetes mellitus
Dullaart, R. P. F. (1995) · The Netherlands Journal of Medicine · doi:10.1016/0300-2977(94)00048-e · Cited by 47
Postprandial lipid metabolism in relation to coronary heart disease
Karpe, F. (1997) · Proceedings of The Nutrition Society · doi:10.1079/pns19970067 · Cited by 47
“Furthermore, Mann et al. (1991) have shown that the exchange of cholesteryl esters is enhanced with increasing plasma triacylglycerol levels in normotriacylglycerolaemic plasma, in contrast to hypertriacylglycerolaemic plasma, in which the excess of acceptor lipoprotein is sufficient to allow CETP…”
Background
Lipoprotein profile and cholesteryl ester transfer protein in neonates
Kaser, S., Ebenbichler, C. F., Wolf, H. J., Sandhofer, A., Stanzl, U., Ritsch, A., & Patsch, J. R. (2001) · Metabolism · doi:10.1053/meta.2001.23307 · Cited by 46
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“Indeed, elevated total plasma TRL levels have been shown to increase CE mass transfer from HDL.21,24 Moreover, according to the observation of Mann et al,21 who reported elevated CETP activity in hypertriglyceridemic subjects due to a marked (fourfold) increase in VLDL levels, postprandial lipemia would be expected to…”
BackgroundInfluential
Regulation of lipid transfer between lipoproteins by an endogenous plasma protein: selective inhibition among lipoprotein classes.
Morton, R. E., & Greene, D. J. (1994) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39178-1 · Cited by 46
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“We have proposed that this increased CETP activity on HDL happens because plasma TG, not CETP, is rate-limiting for net lipid transfer in normal plasma (6, 7).”
Background
Estrogen-induced small low density lipoprotein particles may be atherogenic in postmenopausal women
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Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in Type II diabetics and normal controls
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“These normal functions of CETP may be impaired, since E0 and LDLr0 mice do not have hypertriglyceridemia (13–15), which normally drives the cholesteryl ester transfer process (31, 32).”
Background
Sex-Dependent Association of a Genetic Polymorphism of Cholesteryl Ester Transfer Protein with High-Density Lipoprotein Cholesterol and Macrovascular Pathology in Type II Diabetic Patients
Durlach, A., Clavel, C., Girard-Globa, A., & Durlach, V. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6064 · Cited by 43
“... suggests that genetic variability of the CETP gene is likely to also have an impact on the lipid profile of NIDDM patients, but reports on the subject are few (8, 9). We have addressed the issue in a series of 406 unrelated male and female NIDDM patients explored for micro- and macrovascular complications, with pa…”
Background
Higher high density lipoprotein cholesterol associated with moderate alcohol consumption is not related to altered plasma lecithin: cholesterol acyltransferase and lipid transfer protein activity levels
Riemens, S. C., van Tol, A., Hoogenberg, K., van Gent, T., Scheek, L. M., Sluiter, W. J., & Dullaart, R. P. F. (1997) · Clinica Chimica Acta · doi:10.1016/s0009-8981(96)06451-0 · Cited by 42
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“In line with earlier observations (24, 25), a higher CET was observed in HTG patients than in normolipidemic”
Result
Treatment options for hypertriglyceridemia: From risk reduction to pancreatitis
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Polyacrylamide Gradient Gel Electrophoresis of Lipoprotein Subclasses
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Orth, M., Weng, W., Funke, H., Steinmetz, A., Assmann, G., Nauck, M., Dierkes, J., Ambrosch, A., Weisgraber, K. H., Mahley, R. W., et al. (1999) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.19.5.1306 · Cited by 42
Beneficial properties of olive oil
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“Simply stated, higher levels of TG in apoB-containing particles drives increased CETP activity by increasing availability of TG substrate [37].”
Background
Differing Effects of Pancreas-kidney Transplantation With Systemic Versus Portal Venous Drainage on Cholesteryl Ester Transfer in IDDM Subjects
Bagdade, J. D., Ritter, M. C., Kitabchi, A. E., Huss, E., Thistlethwaite, R. J., Gaber, A. O., & Lambeth, H. (1996) · Diabetes Care · doi:10.2337/diacare.19.10.1108 · Cited by 40
“The CETP substrates that have been shown to exert a strong positive influence on the rate of CET are the concentrations of the CE acceptor lipoproteins VLDL (10) and LDL (21).”
Background
Alterations in composition and concentration of lipoproteins and elevated cholesteryl ester transfer in non-insulin-dependent diabetes mellitus (NIDDM)
Elchebly, M., Porokhov, B., Pulcini, T., Berthézène, F., & Ponsin, G. (1996) · Atherosclerosis · doi:10.1016/0021-9150(95)05789-7 · Cited by 39
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“The triglyceride and esterified cholesterol contained in VLDL particles are transferred to other lipoprotein species by cholesteryl ester transfer protein (CETP).(32) Hence, hypertriglyceridaemia leads to an increase in the production of triglyceride-rich VLDL, and an increase in the transfer of triglyceride to circul…”
Background
Induction of net mass lipid transfer reactions in plasma by wine consumption with dinner
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Relationship between cholesteryl ester transfer protein and LDL heterogeneity in familial hypercholesterolemia
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“tabolism, specifically LDL remodeling (29, 30).”
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Normolipidemic Subjects With Low HDL Cholesterol Levels Have Altered HDL Subpopulations
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Taq1B polymorphism of cholesteryl ester transfer protein (CETP) gene in primary combined hyperlipidaemia.
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Lipid Transfer Inhibitor Protein Defines the Participation of Lipoproteins in Lipid Transfer Reactions
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Plasma lipoprotein distribution and lipid transfer activities in patients with type IIb hyperlipidemia treated with simvastatin
Lagrost, L., Athias, A., Lemort, N., Richard, J.-L., Desrumaux, C. M., Châtenet-Duchêne, L., Courtois, M., Farnier, M., JACOTOT, B., Braschi, S., et al. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(98)00299-8 · Cited by 36
“[41], CETP mass levels would be in excess in plasma from patients with moderate hypertriglyceridemia, and net mass lipid transfers, which are susceptible to alter the distribution of lipid species between various lipoprotein fractions, would be largely dependent on triglyceride levels.”
Background
Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes
Dullaart, Riemens, Scheek, & van Tol, A. (1999) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1999.00521.x · Cited by 36
Postprandial cholesteryl ester transfer and high density lipoprotein composition in normotriglyceridemic non-insulin-dependent diabetic patients
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Acute and chronic effects of a 24-hour intravenous triglyceride emulsion challenge on plasma lecithin: cholesterol acyltransferase, phospholipid transfer protein, and cholesteryl ester transfer protein activities
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Variants in the cholesterol ester transfer protein and lipoprotein lipase genes are predictors of plasma cholesterol response to dietary change
Wallace, A. J., Mann, J. I., Sutherland, W. H. F., Williams, S., Chisholm, A. W., Skeaff, C. M., Gudnason, V. G., Talmud, P. J., & Humphries, S. E. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(99)00490-6 · Cited by 35
“Plasma CETP concentration does not appear to be rate-limiting for cholesteryl ester transfer when plasma triglyceride levels are below about 3 mmol/l [39].”
Background
Lipid Regulation in Lipodystrophy Versus the Obesity-Associated Metabolic Syndrome: The Dissociation of HDL-C and Triglycerides
Joseph, J., Shamburek, R. D., Cochran, E. K., Görden, P., & Brown, R. J. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1878 · Cited by 34
“The resultant triglyceride-rich HDL-C is a good substrate for hydrolysis by hepatic lipase, which has increased activity in insulin resistance (16), and is cleared rapidly from the circulation (17, 18).”
Background
HbA1c negatively correlates with LCAT activity in type 2 diabetes
Nakhjavani, M., Esteghamati, A., Esfahanian, F., Ghanei, A., Rashidi, A., & Hashemi, S. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.01.018 · Cited by 34
“However, plasma triglycerides can confound any potential association because they are a major determinant of cholesterol esterification rate [10,18,19].”
Background
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Authors: Mann, C. J., Yen, F. T., Grant, A. M., & Bihain, B. E.
Affiliations: Louisiana State University (US)
ORCID: Yen, F T
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1991-12-01
Volume: 88
Issue: 6
Pages: 2059-2066
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci115535
OpenAlex: W2114689977
Cited by: 339
References: 30
Citations by year: 2024: 5 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 10 · 2013: 1 · 2012: 2
FWCI: 17.17
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p01hl025596-15)
National Heart, Lung, and Blood Institute (HL255-96)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Keywords: cholesteryl ester transfer, cholesteryl ester transfer protein, hypertriglyceridemia, VLDL, VLDL triglycerides, reverse cholesterol transport, CETP activity, bezafibrate, lipoprotein metabolism, rate-determining step
MeSH terms: Adult, Bezafibrate, Biological Transport, Carrier Proteins, Cholesterol Esters, Glycoproteins, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Lipoproteins, VLDL, Triglycerides, Hypertriglyceridemia, Cholesterol Ester Transfer Proteins

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Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia.

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