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Objective— Anacetrapib (ANA), an inhibitor of cholesteryl ester transfer protein (CETP) activity, increases plasma concentrations of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apoA)-I, apoA-II, and CETP. The mechanisms responsible for these treatment-related increases in apolipoproteins and plasma CETP are unknown. We performed a randomized, placebo (PBO)-controlled, double-blind, fixed-sequence study to examine the effects of ANA on the metabolism of HDL apoA-I and apoA-II and plasma CETP. Approach and Results— Twenty-nine participants received atorvastatin (ATV) 20 mg/d plus PBO for 4 weeks, followed by ATV plus ANA 100 mg/d for 8 weeks (ATV-ANA). Ten participants received double PBO for 4 weeks followed by PBO plus ANA for 8 weeks (PBO-ANA). At the end of each treatment, we examined the kinetics of HDL apoA-I, HDL apoA-II, and plasma CETP after D3-leucine administration as well as 2D gel analysis of HDL subspecies. In the combined ATV-ANA and PBO-ANA groups, ANA treatment increased plasma HDL-C (63.0%; P P P =0.002) without changes in production rate. Although the apoA-II levels increased by 12.6% ( P P P Conclusions— ANA treatment increases HDL apoA-I and CETP levels by decreasing the fractional clearance rate of each protein.

Background According to epidemiological studies, there is no clear relationship between the plasma cholesteryl ester transfer protein (CETP) concentration and the development of atherosclerosis in human populations. Although some studies suggest that increased CETP activity relates to undesirable profiles of plasma lipoproteins, promoting an anti-atherogenic plasma lipoprotein profile by drugs that inhibit CETP has not succeeded in preventing atherosclerosis in humans. Materials and Methods This review describes 28 investigations in human populations dealing with plasma CETP, 11 in mice that express human CETP and seven in animals (six in rabbits and one in mice) in which plasma CETP activity was inhibited by drugs. Results Present review shows that models in mice expressing human CETP are not illuminating because they report increase as well reduction of atherosclerosis. However, investigations in rabbits and mice that develop severe hypercholesterolaemia clearly indicate that impairment of the plasma CETP activity elicits protection against the development of atherosclerosis; in all of these experiments are attained substantial reductions of the atherogenic lipoproteins, namely, plasma apoB containing lipoproteins. Conclusion These models are strong indicators that the benefit in preventing atherosclerosis should be earned in cases of hyperlipidemia by CETP inhibitors.

Repetitive exercise and physical training is well correlated with a reduction of the risk of atherosclerosis, coupled with an increase in serum high density lipoprotein-cholesterol (HDL-C) (Kraus et al. 2002). Plasma apoA-I and HDL-cholesterol levels are also evidently higher in trained athletes than in sedentary age-matched reference people (Sasaki et al. 1988). Regular exercise is known to be advantageous with regard to lipid and lipoprotein metabolism in healthy normolipidemic men and women, and these benefits include an elevation of plasma HDL-cholesterol and a reduction in LDL-cholesterol and plasma cholesteryl ester transfer protein ability (Couillard et al. 2001; Seip et al. 1993).

Plasma cholesteryl ester transfer protein (CETP) inhibitors are currently considered as potential drugs for treating high low-density lipoprotein cholesterol. In this work, we developed a receptor-based quantitative structure–activity relationship (QSAR) models based on a series of tetrahydronaphthyridines derivatives to support the design of new CETP inhibitors. Multivariate adaptive regression spline and adaptive neuro-fuzzy inference system were employed to select the best subset of descriptors and mapping tool. The obtained QSAR model indicates that the inhibitory activity can be described by relative negative charge, Moriguchi octanol–water partition coefficient, topological electronic indices, steric interaction, and hydrogen bonding energies between the receptor and the inhibitors. In addition, the docking analysis showed that the interaction of the inhibitors with residues of the ARG201 and ASP460 residues plays an important role in the activities of the inhibitors. The results of validation and applicability domain techniques show that the models exhibited optimum stability and good predictive power which can be used in prediction of activity of new CETP inhibitors.

High-density lipoprotein (HDL) is an antiatherogenic lipoprotein involved in the reverse cholesterol transport (RCT), which involves cholesterol efflux and its transport back to the liver. HDL has a variety of antiatherogenic functions; however, it can sometimes become dysfunctional. A condition of extremely high serum HDL-cholesterol levels is called “hyperalphalipoproteinemia (HALP).” HALP is a disorder of RCT. The most important genetic basis of HALP is the deficiency of plasma cholesteryl ester transfer protein (CETP). Patients with CETP deficiency demonstrate marked abnormalities in the properties and functions of their lipoproteins. Recent reports indicate that CETP deficiency may not be protected from atherosclerosis. HALP is also caused by abnormalities of molecules involved in RCT such as scavenger receptor class B type I, hepatic lipase, and endothelial lipase. The current review focuses on the molecular mechanisms and clinical significance of HALP.

We studied the relationship between apo E polymorphism and cholesteryl ester transfer protein (CETP) activity in 127 type 2 diabetic patients who did not take lipid lowering drugs. Furthermore, we studied the relationship between apo E and cholesteryl ester transfer protein (CETP) in modulating plasma triglyceride and HDLcholesterol. Apo E genotypes were determined by PCR-RFLP, and CETP activity was measured using an exogenous way. Our results showed that the CETP activity increased significantly in the E2 carrier group compared to E4 carriers and E3/E3 homozygous (84.7 ± 43.9 vs. 62.5 ± 35.9 vs. 52.6 ± 23.6 nmol CE/ml/2h, respectively; p = 0.015). However, there was no association between apo E polymorphism and lipid parameter variations. Even after adjustment for CETP activity, the results remained unchanged, showing that CETP did not step in the relationship between apo E and lipid parameter variations. In conclusion there is an association between apo E polymorphism and CETP activity, and this association did not affect the relationship between apo E polymorphism and triglyceride and HDLcholesterol concentrations.

IF 4.798; International audience; Introduction: Over recent decades, attempts to ascertain the pro-atherogenic nature of plasma cholesteryl ester transfer protein (CETP) and to establish the relevance of its pharmacological blockade as a promising high density lipoproteins-raising and anti-atherogenic therapy have been disappointing.Areas covered: The current review focuses on CETP as a multifaceted protein, on genetic variations at the CETP gene and on their possible consequences for cardiovascular risk in human populations. Specific attention is given to physiological modulation of endogenous CETP activity by the apoC1 inhibitor. Finally, the rationale behind the need for selection of patients to treat is discussed in the light of recent studies.Expert opinion: At this stage one can only speculate on the clinical outcome of pharmacological CETP inhibitors in high-risk populations, but recent advances give cause to adjust the expectations from now on. The CETP effect is probably largely influenced by the overall metabolic state, and whether CETP blockade may be relevant or not in promoting cholesterol disposal is still questioned. The possible need for a careful stratification of patients to treat with CETP inhibitors is outlined. Finally, manipulation of CETP activity should be considered with caution in the context of sepsis and infectious diseases.

Objective: To determine the effect of short-term weight loss in obese women on concentrations of plasma cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), two new risk factors for cardiovascular disease. Research Methods and Procedures: Plasma CETP and PLTP mass concentrations were measured in 38 obese, non-diabetic women before and after a moderate, 4% weight loss that was obtained by a 1250 kcal/d diet for 4 weeks. Anthropometric and biological parameters were measured before and after weight loss. Results: Plasma CETP concentration decreased substantially after weight loss (2.76 ± 0.79 before and 2.31 ± 0.69 mg/L after; p = 0.000), and the same was true for plasma PLTP concentration (9.01 ± 2.44 mg/L before vs. 8.34 ± 2.57 after; p = 0.043). The HDL profile shifted toward the small-sized range, with significant decreases in the relative abundance of HDL2b and HDL2a at the expense of HDL3b after weight loss. A significant, positive correlation between CETP and PLTP mass concentrations is reported for the first time in obese patients (r = 0.43, p = 0.004), and weight reduction was accompanied by early, concomitant, and parallel decreases in plasma CETP and PLTP levels (r = 0.47, p = 0.003). The significant relationship between CETP and PLTP levels was lost after the dietary intervention (r = 0.27; p = 0.11). Discussion: CETP and PLTP correlate positively and significantly in obese patients. The hypocaloric dietary manipulation constitutes a relevant intervention to reduce rapidly and simultaneously plasma levels of CETP and PLTP. The impact of reduced PLTP activity on HDL size appeared to be more prominent than the impact of concomitant reduction in CETP activity.

Plasma cholesteryl ester transfer protein (CETP) has a profound effect on neutral lipid transfers between HDLs and apolipoprotein B (apoB)-containing lipoproteins when it is expressed in combination with human apoA-I in HuAI/CETP transgenic (Tg) rodents. In the present study, human apoA-I-mediated lipoprotein changes in HuAI/CETPTg rats are characterized by 3- to 5-fold increments in the apoB-containing lipoprotein-to-HDL cholesterol ratio, and in the cholesteryl ester-to-triglyceride ratio in apoB-containing lipoproteins. These changes occur despite no change in plasma CETP concentration in HuAI/CETPTg rats, as compared with CETPTg rats. A number of HDL apolipoproteins, including rat apoA-I and rat apoC-I are removed from the HDL surface as a result of human apoA-I overexpression. Rat apoC-I, which is known to constitute a potent inhibitor of CETP, accounts for approximately two-thirds of CETP inhibitory activity in HDL from wild-type rats, and the remainder is carried by other HDL-bound apolipoprotein inhibitors. It is concluded that human apoA-I overexpression modifies HDL particles in a way that suppresses their ability to inhibit CETP. An apoC-I decrease in HDL of HuAI/CETPTg rats contributes chiefly to the loss of the CETP-inhibitory potential that is normally associated with wild-type HDL.

Background and aim Type 2 diabetes mellitus is associated with atherosclerosis, which has been, in part, ascribed to abnormalities in the reverse cholesterol transport system. Among the key actors involved in this pathway is cholesteryl ester transfer protein (CETP) which mediates the transfer of cholesteryl esters (CE) from HDL to apoB-containing lipoproteins. Methods and results The purpose of this study was to examine CETP activity in 220 patients with type 2 diabetes mellitus (type 2 DM) treated with diet alone or diet and sulphonylurea drugs and to identify the factors that may regulate it in the diabetic state. We also examined the effect of diet on the activity of plasma CETP in a subgroup of type 2 DM women. CETP activity was assessed by measuring plasma-mediated cholesteryl ester transfer (CET) between pooled exogenous HDL and apoB-containing lipoproteins. In 220 patients with type 2 DM, CET was significantly higher in conjunction with higher plasma triglycerides and lower HDL-cholesterol compared to 100 matched healthy controls. Correlation analysis showed that CETP activity was significantly correlated with the HDL-C to apoA1 ratio ( r =−0.205, P =0.003) and to LDL-C to HDL-C ratio in diabetic women ( P =0.010). Furthermore, CETP activity was correlated marginally with total energy intake ( P =0.052) but to a statistically significant extent with the amount of fat consumed daily ( P =0.008). A significant negative correlation was found between plasma CETP activity and MUFA of plasma phospholipids or free PUFA ( P =0.032), especially with ω3-fatty acids ( P =0.001). Conclusion Our findings indicate that CET is accelerated in patients with type 2 DM and that this may be regulated by dietary fatty acids in the diabetic state.

Cholesteryl ester transfer protein (CETP) mediates the bidirectional exchange of cholesteryl esters (CEs) and triglycerides between HDL and LDL (1)⁠. Animal models along with early clinical studies have demonstrated that the impairment of CETP's functionality is important for the efficient treatment of cardiovascular diseases. Despite the pharmacological interest, CETP's lipid transfer mechanism is poorly understood. Recent cryo-electron microscopy studies suggested that CETP penetrates its N-and C-terminal β-barrel domains into HDL and LDL respectively to form a ternary complex (2)⁠. Further it was proposed that the hydrophobic tunnel of CETP can simultaneously interact with the core of HDL and LDL for continuous lipid exchange. However, the detailed lipid transfer process is still inconclusive. In this study, we employed coarse-grained molecular dynamics simulations to illuminate the lipid transfer mechanism of CETP in HDL-CETP-LDL ternary complex. The extent of penetration of CETP into HDL and LDL in our ternary complex model corroborated well with the experimental findings. Further, the results demonstrated that the ejection of C-terminal plug-in phospholipid (PLC) and subsequently the diffusion of CETP-bound CEs into LDL droplet through PLC opening. A detailed analysis on interactions of PLC pocket lining residues with the discharged lipids revealed residues with significant role in CE transfer. The detailed mechanism of lipid transfer by CETP as explored in this study might help designing future CETP research and subsequent CETP therapeutics.References:1. Tall, A.R. Plasma cholesteryl ester transfer protein. J. Lipid Res. 34: 1255–1274 (1993).2. Zhang, L. et al., Structural basis of transfer between lipoproteins by cholesteryl ester transfer protein. Nat. Chem. Biol. 8: 342–349 (2012).

We investigated the effects of HMG-CoA reductase inhibitors (statins) on the activity and concentration of plasma cholesterol ester transfer protein (CETP) in 30 hypercholesterolemic patients. Patients were divided into three groups according to TaqIB polymorphism of the CETP gene. The activity (158 +/- 23% control, mean +/- SEM) and concentration (4.1 +/- 1.0 mg/l) of plasma CETP were significantly (p < 0.005) higher in the subjects with the B1B1 genotype than B2B2 genotype (106 +/- 25% and 2.5 +/- 1.1 mg/l, respectively). Plasma CETP activity and concentration levels in the B1B2 group were intermediate between those of the B1B1 and B2B2 groups, and significantly (p < 0.05) low compared with the B1B1 group.Both the activity and concentration of plasma CETP were positively correlated with the LDL-cholesterol concentration (r = 0.608, p < 0.0005 and r = 0.552, p < 0.005, respectively). The administration of statins significantly reduced not only the activity (p < 0.01) but also the concentration (p < 0.05) of plasma CETP in hypercholesterolemic patients. Taken together, we confirmed that statins would be effective in increasing HDL levels in Japanese B1B1 carriers, because of a lower concentration of HDL cholesterol and higher level of plasma CETP compared to the other genotypes. The genetic variation in the CETP gene may be one important factor in designing better treatments.

Objectives: Cholesteryl ester transfer protein (CETP) mediates the transfer of HDL cholesterol to apoB-containing lipoproteins. Its mass and activity are increased in several pro-atherogenic conditions. The objective of this study is to develop a cost- and time-effective sandwich ELISA for plasma CETP concentration. Design and methods: Monoclonal anti-CETP, TP20, was used as the capture antibody, while the other biotinylated monoclonal anti-CETP, TP2, was used for detection. The results were expressed in an arbitrary unit, ng biotin-TP2 bound per μl plasma. Plasma CETP concentrations, activities and their relationship were assessed in 35 IDDM children. Results: The assay had an intra-assay CV of 8.75% and an inter-assay CV under 10%. Plasma CETP concentration of these subjects ranged from 0.36–1.89 ng biotin-TP2/μL. CETP concentration was significantly correlated with CETP activity (r = 0.51, p < 0.01). Conclusion: The sandwich ELISA we have developed carried sufficient sensitivity for assaying plasma CETP concentration in human.

Plasma cholesteryl ester transfer protein (CETP) concentrations were measured in Japanese subjects by an ELISA with two different monoclonal antibodies that were raised against rabbit CETP and cross-reacted against human CETP. Among 63 patients who consecutively underwent coronary angiography, the plasma CETP of 37 patients with luminal stenosis ≥50% in their coronary arteries was not significantly different from that of the 26 patients with luminal stenosis

Plasma cholesteryl ester transfer protein facilitates the transfer of cholesteryl ester from HDL to apolipoprotein B-containing lipoproteins, and is a key protein in the reverse cholesterol transport system. The importance of plasma cholesteryl ester transfer protein in lipoprotein metabolism was highlighted by the discovery of deficient individuals with a marked hyper-HDL-cholesterolemia. Cholesteryl ester transfer protein deficiency causes various abnormalities in the concentration, composition, and functions of both HDL and LDL. Its significance in atherosclerosis is still controversial. However, in-vitro evidence shows large cholesteryl ester-rich HDL particles in cholesteryl ester transfer protein deficiency are defective in cholesterol efflux. Recent epidemiological studies have demonstrated an increased incidence of coronary atherosclerosis in deficient patients. The current review will also focus on the molecular genetics of the protein.

In many individuals, LDL-cholesterol levels rise following increased consumption of dietary cholesterol or saturated and trans-monounsaturated fatty acids. In others, a reduction of cholesterogenesis fully compensates for these effects. In responding individuals, much of the increase in LDL-cholesterol observed may result directly from an increase in plasma cholesteryl ester transfer protein activity whose effect is not mediated by hepatic LDL receptors.

The effects of palmitic and stearic acid-enriched diets on serum lipids, lipoproteins, apolipoproteins (apo) A-I and B, and plasma cholesteryl ester transfer protein (CETP) activity were examined in 12 healthy young women. Subjects followed the two experimental diets for 4 weeks according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 weeks. The diets provided 37% of total energy intake (E%) as fat, and differed only with respect to fatty acid composition. There was a substitution of 5E% of palmitic acid or stearic acid in the experimental diets for 5E% of monounsaturated fatty acids in the baseline diet. After the palmitic acid diet, serum total and high-density lipoprotein (HDL) cholesterol and apo A-I concentrations were higher (8%, P = .015, 9%, P = .040, and 11%,P = .011, respectively) and mean serum low-density lipoprotein (LDL) cholesterol concentration tended to be higher (8%, P = .077) as compared with values after the stearic acid diet. Plasma CETP activity increased in the palmitic acid diet as compared with the stearic acid diet (12%, P = .006). In conclusion, palmitic acid and stearic acid-enriched diets had different effects on serum lipids and lipoproteins and also on plasma CETP activity in young healthy women.

We studied the effects of simvastatin treatment on plasma cholesterylester transfer protein (CETP) activity and lipid levels in patients with type IIa hypercholesterolemia. We treated 24 patients, 4 men and 20 women aged 49 to 81 years (mean age, 64.5 ± 8.5 years), with simvastatin at a daily dose of 5 mg for 4 weeks. Simvastatin treatment significantly decreased plasma total cholesterol (262 ± 28 mg/dL vs 220 ± 28 mg/dL) and low-density lipoprotein cholesterol (LDL-C)(181 ± 26 mg/dL vs 135 ± 28 mg/dL) and significantly increased high-density lipoprotein cholesterol (HDL-C) (57.2 ± 8.4 mg/dL vs 62.8 ± 10.5 mg/dL. CETP activity significantly decreased after 4 weeks of treatment (11.2 ± 3.8%/10 μL/3 h vs 8.9 ± 3.8% 10 μL/3 h. These results suggest that one of the lipid-lowering effects of simvastatin is due to decreased CETP activity, which results in decreased LDL-C and increased HDL-C concentrations.

ApoA-I-containing lipoproteins exist in plasma in two main forms: one contains only apoA-I (LpA-I) while the other contains both apoA-I and apoA-II (LpA-I/A-II). We characterized structural and functional changes of these lipoproteins in six patients with cholesteryl ester transfer protein (CETP) deficiency. In these patients, the amount of LpA-I and LpA-I/A-II had increased significantly. Sixty-five percent of plasma apoA-I was associated with LpA-I/A-II, which indicated that LpA-I/A-II was predominant. The chemical composition of both LpA-I and LpA-I/A-II was characterized by increased ratios of neutral to polar lipid, compared with findings in normal subjects. Particle sizes of these lipoproteins shifted to larger diameter ranges, as compared to the size seen in normal subjects. Incubation of patients' LpA-I and LpA-I/A-II with CETP markedly corrected the chemical and physical abnormalities in these lipoproteins. Cholesterol-reducing capacities of these lipoproteins from macrophage foam cells were significantly lower than in normal controls. Cholesterol esterification rates in LpA-I, LpA-I/A-II, and plasma were significantly lower in patients than in normal controls. We propose that the structure and function of LpA-I and LpA-I/A-II are severely affected in the presence of CETP deficiency.

Clinical trials using cholesteryl ester transfer protein (CETP) inhibitors to raise high-density lipoprotein cholesterol (HDL-C) concentrations reported an 'off-target' blood pressure (BP) raising effect. We evaluated the relations of baseline plasma CETP activity and longitudinal BP change.One thousand, three hundred and seven Framingham Study participants free of cardiovascular disease attending consecutive examinations 4 years apart (mean age 48 years) had baseline plasma CETP activity related to change in BP over the 4-year interval, adjusting for standard risk factors. Systolic BP increased [median +2 mmHg, 95% confidence interval (CI) -16,+23 mmHg], whereas diastolic BP decreased (median -3 mmHg, 95% CI -15,+11 mmHg). Plasma CETP activity was not related to change in diastolic BP, but was inversely related to change in systolic BP that was borderline significant (P=0.09). On multivariable analyses, plasma CETP activity was inversely related to change in pulse pressure (PP; beta per SD increment= -0.71 mmHg, P=0.005). When dichotomized at the median, plasma CETP activity above the median was associated with a 1 mmHg lower PP on follow-up (P=0.045).Decreasing plasma CETP activity was modestly related to increasing PP on follow-up in our community-based sample, suggesting that inhibition of intrinsic CETP activity itself is likely associated with minimal changes in BP.

Studies were conducted in rabbits and rats to investigate the effects of diets rich in oleic (CIS diet), palmitic (SAT diet) and trans fatty acids (TRANS diet) on plasma lipids and lipoprotein metabolism. An important difference between these species is that rabbits possess plasma cholesteryl ester transfer protein (CETP) activity while rats are devoid of transfer activity. In the presence of dietary cholesterol (0.2% w/w) the change in plasma low density lipoprotein-cholesterol (LDL-C) concentration from baseline was significantly higher in rabbits fed the TRANS diet compared with those fed the CIS diet (P0.01). Despite this difference, the hepatic LDL-receptor activity was similar in all groups. Also, the fatty acid composition of hepatic phospholipids was affected by diet with lower proportion of palmitic (11%) and higher (19%) linoleic acid despite a similar content in the diet. These effects may represent the maintenance of membrane fluidity within narrow limits to ensure optimal function. The studies in rats showed that the plasma total cholesterol concentration was 20% lower (P0.01) in TRANS-fed rats compared with those fed the CIS diet. The results of an in vivo assay of reverse cholesterol transport (RCT) suggested that the three diets gave rise to high density lipoprotein (HDL) particles with similar capacity to accept cellular cholesterol. The differential effects of dietary trans fatty acids in these animal models provide another line of evidence that reinforces the significant role of CETP activity in determining the distribution of plasma cholesterol in response to dietary trans fatty acids.

Plasma cholesteryl ester transfer protein plays a central role in lipoprotein metabolism by exchanging cholesteryl esters with triglycerides. Human genetic deficiency is associated with increased HDL-cholesterol levels, whereas cholesteryl ester transfer protein overexpression in transgenic mice results in decreased HDL-cholesterol. Thus, it has been proposed that cholesteryl ester transfer protein deficiency is an antiatherogenic state. However, recent observations in human cholesteryl ester transfer protein deficiency and cholesteryl ester transfer protein transgenic mice also suggest antiatherogenic effects of the expression of this protein, probably reflecting its role in reverse cholesterol transport.

Plasma cholesteryl ester transfer protein (CETP) activity was measured in 52 alcoholics and 38 controls and compared with conventional laboratory markers of alcoholism. Mean daily alcohol intake was 180 g/day among the alcoholics and 10 g/day among the controls. Plasma CETP activity was 26% lower in the alcoholics ( P < 0.001) and was inversely correlated with daily alcohol intake ( r = −0.288, P < 0.05). CETP activity detected 63% of the alcoholics, and its specificity was 82% if the cut-off point was set at the mean CETP activity of the controls −1 SD. The mean −2 SD gave a very low sensitivity for CETP (8%) and cannot be used as its cut-off point. The sensitivities and specificities of gamma glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, mean corpuscular volume and high-density lipoprotein cholesterol were similar to those of CETP activity when the cut-off point for CETP was mean −1 SD. The results thus indicate that plasma CETP activity is not sufficient as a single marker of alcoholism but could be used as an additional method to detect alcohol misuse, although its wide variation in normal population and the elaborate analysis limit its usefulness.

This study compares the specificities of selective uptake and transfer mediated by plasma cholesteryl ester transfer protein (CETP) for various species of cholesteryl esters in high density lipoproteins (HDL). [3H]Cholesterol was esterified with a series of variable chain length saturated acids and a series of variably unsaturated 18-carbon acids. These were incorporated into synthetic HDL particles along with 125I-labeled apoA-I as a tracer of HDL particles and [14C]cholesteryl oleate as an internal standard for normalization between preparations. Selective uptake by Y1-BS1 mouse adrenal cortical tumor cells was most extensively studied, but uptake by human HepG2 hepatoma cells and fibroblasts of human, rat, and rabbit origin were also examined. Acyl chain specificities for selective uptake and for CETP-mediated transfer were conversely related; selective uptake by all cell types decreased with increasing acyl chain length and increased with the extent of unsaturation of C18 chains. In contrast, CETP-mediated transfer increased with acyl chain length, and decreased with unsaturation of C18 chains. The specificities of human and rabbit CETP were also compared, and were found to differ little. Associated experiments showed that HDL-associated triglycerides, traced by [3H]glyceryl trioleyl ether, were selectively taken up but at a lesser rate than cholesteryl esters. The mechanism of this uptake appears to be the same as for selective uptake of cholesteryl esters.