Chylomicron Remnant Metabolism Research Articles

Relative roles of LDLr and LRP in the metabolism of chylomicron remnants in genetically manipulated mice

Remnant-like emulsions labeled with cholesteryl [13C]-oleate were prepared with lipid compositions similar to remnants derived from triacylglycerol-rich lipoproteins. When injected into the bloodstream of conscious mice, the remnant-like emulsions were metabolized in the liver leading to the appearance of 13CO2 in the breath. Previously, using this technique, we found that remnant metabolism was significantly impaired but not completely inhibited in mice lacking low density lipoprotein receptors (LDLr). We have now found in mice with non-functional low density lipoprotein receptor-related protein (LRP) that breath enrichment of 13CO2 was significantly decreased, indicating that the LRP also plays an important role in the metabolism of chylomicron remnants (CR). The enrichment of 13CO2 in the expired breath was negligible in mice lacking both LDLr and receptor-associated protein (−/−), essential for normal function of LRP. In mice pre-injected with gluthatione S-transferase–receptor-associated protein to block LRP binding, there was a marked inhibition of the appearance of 13CO2 in the expired breath of homozygous LDLr-deficient mice, supporting the role of LRP in vivo. Whether or not LDLr were present, in mouse and human fibroblast cells human apoE3 or E4 but not apoE2 were essential for binding of remnant-like emulsions, while lactoferrin and suramin completely inhibited binding. We conclude that in normal mice LDLr are important for the physiological metabolism of CR. When LDLr are absent the evidence supports a role for the LRP in the uptake of CR in liver cells and in fibroblasts, with binding characteristics for CR-associated apoE similar to LDLr. —Martins, I. J., E. Hone, C. Chi, U. Seydel. R. N. Martins, and T. G. Redgrave. Relative roles of LDLr and LRP in the metabolism of chylomicron remnants in genetically manipulated mice.

Multiple processes are involved in the uptake of chylomicron remnants by mouse peritoneal macrophages

The processes responsible for the uptake of chylomicron remnants by macrophages were investigated using freshly isolated cells from low density lipoprotein (LDL) receptor, very low density lipoprotein (VLDL) receptor and apolipoprotein E knockout mice. In peritoneal macrophages from normal mice, the metabolism of chylomicron remnants was inhibited 40% by anti-LDL receptor antibody and 60% by a high concentration of receptor-associated protein (RAP). Together they reduced the amount processed by 70%. Digestion of cell proteoglycans decreased remnant degradation by 20% while the addition of acetyl-LDL had no effect. When LDL receptors were absent, the absolute rates of metabolism were less than that of normal cells and were not inhibited by the anti-LDL receptor antibody; the rates, however, were reduced to less than half by RAP. These suggest that the LDL receptor-related protein (LRP) or another LDL receptor family member(s) contributes to chylomicron remnant uptake and becomes the major mechanism of uptake when LDL receptors are absent. In contrast, the VLDL receptor was not involved as its absence did not affect chylomicron remnant metabolism. Similarly, the absence of apoE production did not affect the amount of remnant uptake; however, the proportion that was sensitive to RAP was eliminated. The level of LRP expression was not altered in these cells whereas there was a decrease in LDL receptors. This suggests that the apoE content of chylomicron remnants is sufficient for its recognition by LDL receptors but additional apoE is required for its uptake by the LRP and that there is an up-regulation of a non-LDL receptor family mechanism in apoE deficiency. Together these studies suggest that even in the absence of LDL receptors or apoE secretion, chylomicron remnants could contribute to lipid accumulation in the artery wall during atherogenesis.

Comparison of short- and long-term effects of different dietary fats on the hepatic uptake and metabolism of chylomicron remnants in rats.

The uptake and metabolism of [14C]oleate-labelled chylomicron remnants derived from olive oil, maize oil, palm oil, fish oil or butter fat was investigated using perfused livers from rats fed on the corresponding fat-supplemented diet (providing 40% of the dietary energy) or a low-fat diet for 21 d. The percentage of added [14C]oleate-labelled remnant removed from the perfusate was similar for livers from rats fed on the fat-supplemented diets irrespective of the type of fat fed, whereas livers from rats fed on the low-fat diet removed more labelled fish oil and butter fat remnants than olive, maize or palm oil remnants. Following hepatic uptake in the fat-supplemented groups, the oxidation of [14C]oleate-labelled remnant lipid from maize oil, fish oil, and butter fat remnants was greater than that of the lipids from olive and palm oil remnants, although only the oxidation of lipids from maize and palm oil remnants was increased by prior fat-supplementation of the diet. In addition, the livers from rats fed on the fish-oil-supplemented diet incorporated more [14C]oleate-labelled remnant lipid into phospholipid compared with the livers from rats fed on the other fat-supplemented diets or the low-fat diets. These investigations show that both prior fat feeding and the composition of the fat fed, as well as the fatty acid composition of the chylomicron remnant particles themselves, influence the uptake and metabolism of chylomicron remnants by the liver.

Use of gene-manipulated models to study the physiology of lipid transport.

1. In vivo and in vitro gene-manipulated models were used to study the metabolism of chylomicron remnants. Transgenic mice expressing human apolipoprotein (Apo) A1 or E4, gene knockout mice deficient in ApoE or low density lipoprotein (LDL) receptors and antisense gene inhibition in HepG2 cells were used to evaluate the effect of gene manipulations on the metabolism of chylomicron remnants. 2. Mice transgenic for human ApoE4 showed accelerated clearance of chylomicron-like emulsions when animals were fed a low-fat diet. When challenged by a high-fat diet, remnant clearance in ApoE4 transgenic mice was delayed, as in normal or non-transgenic controls. However, unlike normal nontransgenic controls, in ApoE4 transgenic mice high density lipoprotein (HDL)-cholesterol levels remained high after high-fat feeding, which probably protected the animals from the development of atherosclerosis. In contrast, clearance of chylomicron-like lipid emulsions was not affected by the over-expression of human ApoAI in transgenic mice. 3. Gene knock-out mice deficient in ApoE or deficient in the LDL receptor were used to show that ApoE and LDL receptors are both essential for the normal, fast catabolism of chylomicron remnants by the liver. In the absence of the LDL receptor, an alternative ApoE-dependent pathway operates to clear chylomicrons from the plasma, with significantly delayed catabolism. 4. Antisense gene inhibition techniques were used to suppress the expression of syndecan, a core protein of heparan sulfate proteoglycan, in HepG2 cells. Remnant uptake in cells transfected with the antisense oligodeoxynucleotide complementary to a 20 nucleotide sequence upstream of the initiation site of syndecan cDNA markedly reduced the uptake of chylomicron remnant.

Phagocytic degradation of chylomicron remnants by fibroblasts from subjects with homozygous familial hypercholesterolaemia.

1. Familial hypercholesterolaemia is a common genetic abnormality in man characterized by premature atherogenesis as a consequence of disturbed lipoprotein metabolism. Chylomicrons, which represent intestinally derived lipoproteins, are cleared poorly in familial hypercholesterolaemia which may explain the increased retention of chylomicron remnants in arterial fatty lesions. However, cellular uptake of chylomicron remnants in familial hypercholesterolaemia remains unclear. This study determined the quantitative significance of non-low-density lipoprotein receptor-mediated uptake in fibroblasts from subjects with homozygous familial hypercholesterolaemia. 2. The metabolism of chylomicron remnants was assessed in fibroblasts from subjects with homozygous familial hypercholesterolaemia who lack low-density lipoprotein receptors. Compared with fibroblasts from normolipidaemic subjects, binding and degradation of chylomicron remnants was reduced by about two-thirds. Nevertheless, degradation of chylomicron remnants in cells from subjects with familial hypercholesterolaemia persisted in the absence of functioning low-density lipoprotein receptors. 3. Binding of chylomicron remnants to fibroblasts from subjects with familial hypercholesterolaemia was saturable. Unlabelled chylomicron remnants competed efficiently for binding but unlabelled low-density lipoprotein or a monoclonal antibody specific to the human low-density lipoprotein receptor had little effect on binding or degradation. 4. Polyinosinic acid did not alter binding and degradation of chylomicron remnants by fibroblasts from subjects with familial hypercholesterolaemia, ruling out involvement of the scavenger receptor. Lactoferrin was found to inhibit binding and degradation of chylomicron remnants by fibroblasts from subjects with familial hypercholesterolaemia by approximately 50%, implicating involvement of the alpha 2-macroglobulin receptor. 5. Cytochalasin D blocked degradation of chylomicron remnants at 37 degrees C in fibroblasts from subjects with familial hypercholesterolaemia by more than 80% but had no effect on binding at 4 degrees C, consistent with a phagocytic uptake pathway. Collectively, the data suggest that chylomicron remnants bind to a cell-surface protein which initiates phagocytosis and that lactoferrin interferes with binding to this putative cell-surface protein. Phagocytic uptake of chylomicron remnants provides an additional mechanism whereby cells from subjects with familial hypercholesterolaemia can accumulate lipid.

Role of the Low Density Lipoprotein (LDL) Receptor Pathway in the Metabolism of Chylomicron Remnants: A QUANTITATIVE STUDY IN KNOCKOUT MICE LACKING THE LDL RECEPTOR, APOLIPOPROTEIN E, OR BOTH

Two receptor pathways are thought to mediate the hepatic clearance of chylomicron remnants, (i) the low density lipoprotein receptor (LDLR) pathway and (ii) non-LDLR pathway. The current study was undertaken to quantitatively assess the contribution of each receptor pathway to hepatic catabolism of chylomicron remnants, by using mice that are deficient in apolipoprotein E (apoE) (apoE(-/-)), the LDLR (LDLR(-/-)), and both (apoE(-/-);LDLR(-/-)). Vitamin A fat tolerance tests showed that the area under the curves of the plasma excursions of retinyl ester in the LDLR(-/-), apoE(-/-), and apoE(-/-);LDLR(-/-) mice were 4, 12, and 12 times larger than those in wild-type mice. The retinyl ester accumulated in the plasma of the LDLR(-/-) mice was distributed in larger subfractions of triglyceride-rich lipoproteins, chylomicrons through very low density lipoprotein-C. These results indicate that the LDLR constitutes the major pathway for the clearance of retinyl ester. In support of this, agarose gel electrophoresis revealed that an oral fat load resulted in retention of chylomicrons in the LDLR(-/-) mice, which was not seen in wild-type mice. The observation that the apoE(-/-) mice showed larger retinyl ester excursion than LDLR(-/-) mice indicates that an apoE-dependent non-LDLR pathway is involved in the rest of the clearance of the retinyl ester. Together, we conclude that the LDLR pathway plays a significant role in the chylomicron remnant metabolism in mice fed a normal chow.

Intracellular Localization and Metabolism of Chylomicron Remnants in the Livers of Low Density Lipoprotein Receptor-deficient Mice and ApoE-deficient Mice: EVIDENCE FOR SLOW METABOLISM VIA AN ALTERNATIVE apoE-DEPENDENT PATHWAY

The metabolism of chylomicron remnants in mice deficient in low density lipoprotein receptor (LDLr) or apolipoprotein E (apoE) was compared with that of control C57BL/6J mice. Mice were injected intravenously with chylomicron-like emulsions labeled with radioactive lipids. Blood samples were taken at fixed time intervals from the retro-orbital sinus, and clearance rates of the lipoproteins were assessed from the decline in plasma radioactivities. To follow the intracellular pathway of remnants in the liver, emulsions labeled with a fluorescent cholesteryl ester (BODIPY) were injected, and liver sections were processed and assayed by laser confocal microscopy. Catabolism of remnant cholesteryl esters was assessed by injecting emulsions labeled with cholesteryl[1-14C]oleate and measuring the expired CO2 from each animal. In apoE-deficient mice, remnant removal from plasma was totally impeded, while the clearance of remnants in LDLr-deficient mice was similar to that in C57BL/6J control mice. The confocal micrographs of livers 20 min after injection of fluorescent chylomicron-like emulsions showed evenly distributed fluorescent particles in the hepatocytes from control mice. In contrast, the fluorescent particles were mainly located in sinusoidal spaces in LDLr-deficient mice. Three hours after injection the livers from control mice showed few fluorescent particles, indicating that remnants have been catabolized, while the sections from LDLr-deficient mice were still highly fluorescent. Micrographs from apoE-deficient mice showed no fluorescent particles in the liver at any time after injection. Measurement of expired radioactive CO2 after injection of emulsions labeled in the fatty acid moiety of cholesteryl oleate indicated that remnant metabolism was slower in the LDLr-deficient mice and essentially nil in the apoE-deficient mice. Control mice had expired 50% of the injected label by 3 h after injection. We conclude that under normal circumstances, chylomicron remnants are rapidly internalized by LDLr and catabolized in hepatocytes, with a critical requirement for apoE. When LDLr is absent, remnants are taken up by a second apoE-dependent pathway, first to the sinusoidal space of the liver, with subsequent slow endocytosis and slow catabolism. Hepatic clearance via this second pathway is increased by heparin, inhibited by lactoferrin, heparinase, and suramin, and down-regulated by feeding a high fat diet.

Measurement of expired carbon dioxide to assess the metabolism of remnant lipoproteins.

The cholesteryl esters transported from the intestine in chylomicrons are delivered to the liver. Hepatocytes take up chylomicron remnants by receptor-mediated endocytosis and the cholesteryl esters are subsequently degraded. In this study we measured the appearance in breath of labeled carbon dioxide after injection of chylomicron-like emulsions labeled with radioactive cholesteryl [1-14C]oleate. Measurements by the breath test provide an integrated assessment of capacity for clearance and subsequent metabolism of the remnants of the triglyceride-rich lipoproteins. In normal rats, mice, and rabbits injected with the radioactive emulsions, label appeared in the breath after a delay of approximately 30 min, appreciably slower than the appearance of label after injection of emulsions labeled with [14C]triolein or of [14C]oleic acid complexed with albumin. To test for the ability of the procedure to detect defects in remnant clearance, labeled emulsions were injected into diabetic rats, apoE-deficient mice, low density lipoprotein receptor (LDLr)-deficient mice, and Watanabe heritable hyperlipidemic (WHHL) rabbits with defective low density lipoprotein receptors. In rats made diabetic by treatment with streptozotocin the appearance of 14CO2 in breath was slower than in normal control rats. This finding was consistent with previous evidence from our laboratory that remnant clearance is defective in diabetic rats. In LDLr-deficient mice the appearance of 14CO2 was slower when compared with control mice and in apoE-deficient mice the appearance of 14CO2 was extremely small. In homozygous WHHL rabbits, the appearance of 14CO2 in breath was much slower than in normal control rabbits, while in heterozygous WHHL rabbits an intermediate level of appearance was found, consistent with our previous findings of defective remnant clearance in WHHL rabbits. Emulsions with cholesterol omitted, previously found to be cleared from plasma much slower than chylomicron-like emulsions, had much slower appearance of label in breath. The breath test as described is consistent with predicted metabolism of chylomicron remnants and therefore provides a useful means of assessment of remnant catabolism in the intact animal.

Apolipoprotein A-I deficiency. Biochemical and metabolic characteristics.

Familial HDL deficiencies are associated with variable susceptibility to premature coronary heart disease, but the mechanism underlying this association remains poorly understood. Three homozygotes with isolated complete apo A-I deficiency caused by an autosomal codominant apo A-I Q[-2]X mutation and one heterozygote developed coronary heart disease before age 40 years. We characterized the effects of this mutation on lipoprotein metabolism. LDL FC, phospholipid, and apo B were all significantly higher in homozygotes than in heterozygotes. The HDLs of the heterozygotes were apo A-I poor relative to apo A-II. Lecithin-cholesterol acyltransferase activity was 59% lower in homozygotes than in normal subjects or heterozygotes. Cholesteryl ester transfer activity was increased in a homozygote compared with a normolipidemic control subject. Postprandial lipid metabolism was studied in one homozygote and one heterozygote. Post-prandial TG response in the homozygote was significantly exaggerated, while residual plasma HDL level remained unaffected. The homozygote also had delayed clearance of retinyl ester, a marker of chylomicron remnant metabolism. Thus, homozygosity and heterozygosity for apo A-I Q[-2]X are associated with qualitative, as well as quantitative, disturbances in plasma HDLs, LDLs, lipid-modifying enzyme activities, and postprandial retinyl ester metabolism. The observed elevation of atherogenic lipoproteins and reduction in antiatherogenic lipoproteins in the affected members of the apo A-I Q[-2]X kindred are consistent with the primary deficiency in apo A-I having pleiotropic effects that markedly enhance susceptibility for coronary heart disease.

Supplementation of the diet with corn or olive oil enhances the hepatic metabolism of chylomicron remnants

Supplementation of the diet with corn or olive oil enhances the hepatic metabolism of chylomicron remnants

Chylomicron remnant metabolism by macrophages

Chylomicron remnant metabolism by macrophages

Influence of fatty acid saturation on chylomicron remnant metabolism in the perfused liver

Influence of fatty acid saturation on chylomicron remnant metabolism in the perfused liver

The role of alpha 2M receptor/LRP in chylomicron remnant metabolism.

A strong candidate for the long-searched CR receptor might be the alpha 2MR/LRP. Presently, we are overseeing a whole series of in vitro experiments from different laboratories that show that LRP expresses all the features for being such a receptor protein. LRP is localized on the liver cell surface, as well as on most other animal cells. It recognizes apo E-enriched lipoproteins as beta-VLDL and CR. There is evidence that CR contain LPL and it has been demonstrated that LPL binds with high affinity to LRP. This has been shown in cell binding experiments with subsequent cross-linking and in direct assays on purified receptor protein. HL, which is expressed in liver cells and localized at the liver cell surface, is also able to bind to LRP. Moreover, LRP is found in endosomes and can mediate the uptake of beta-VLDL and CR. Further studies are necessary to evaluate its role in vivo as well as its regulation. The interplay between the different ligands of this large multifunctional receptor protein needs to be clarified. It should be emphasized here that, by describing LPL as a new mediator of CR uptake in the liver and by providing evidence for a direct interaction between LPL and LRP, the role of LRP in the remnant catabolism has become even more likely.

Mechanisms regulating hepatic chylomicron remnant uptake and metabolism

Mechanisms regulating hepatic chylomicron remnant uptake and metabolism

Comparison of the hepatic metabolism of chylomicron remnants derived from corn oil or butter fat

Comparison of the hepatic metabolism of chylomicron remnants derived from corn oil or butter fat

Metabolism of Chylomicron Remnants in Transgenic Mice Expressing Apolipoprotein E in the Intestine

Apolipoprotein E (apoE) has high affinity for the cell surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma chylomicron clearance, a transgenic mouse line which overexpresses apoE in the intestine was established. Immunohistochemistry demonstrated that considerable amounts of apoE were localized to mucosal cells of the intestine. In an oral retinyl palmitate challenge test, both the peak height and area under the curve in transgenic mice were less than 25% of those in controls. We speculate that the apoE molecules produced in the intestine of transgenic mice were incorporated onto newly synthesized chylomicron particles before their secretion into the plasma and thereby contributed to rapid plasma clearance of chylomicron remnants. Gene expression of apoE in the intestine would be a promising way to control postprandial hyperlipemia.

Metabolism of triglyceride-rich lipoproteins during alimentary lipemia.

The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia.

In vivo removal of beta-VLDL, chylomicron remnants, and alpha 2-macroglobulin in the rat.

The low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin (alpha 2M) receptor has been suggested as a potential chylomicron remnant receptor. To investigate the involvement of LRP in chylomicron remnant metabolism in vivo, cross-competition experiments with chylomicron remnants, beta-VLDL, and receptor-active alpha 2M, complexed with trypsin (alpha 2M-trypsin), were performed in rats. Saturating concentrations of unlabeled beta-VLDL failed to inhibit the plasma clearance and hepatic uptake of 125I-labeled alpha 2M-trypsin and, vice versa, alpha 2M-trypsin failed to retard the removal of 125I-labeled chylomicron remnants. It has been demonstrated previously that bovine lipoprotein lipase (LPL) strongly enhances the binding of apolipoprotein E-containing lipoproteins to LRP (U. Beisiegel, W. Weber, and G. Bengtsson-Olivecrona. 1991. Proc. Natl. Acad. Sci. USA. 88: 8342-8346). Therefore, beta-VLDL were enriched with isolated LPL or heparin was injected simultaneously with beta-VLDL to increase the concentration of endogenous LPL bound to beta-VLDL. Yet, no inhibition of the plasma elimination and the hepatic uptake of 125I-labeled alpha 2M-trypsin was observed after injection of saturating amounts of beta-VLDL enriched with LPL. We conclude that in the rat triglyceride-rich lipoproteins and alpha 2M-trypsin bind in vivo either to different binding domains of LRP or to a different receptor protein.

Short-term interruption of training affects both fasting and post-prandial lipoproteins

Exercise training alters plasma lipoprotein profiles in a manner compatible with decreased coronary artery disease risk. The aim of this study was to ascertain whether interuption of training (detraining) was associated with potentially undesirable changes in the metabolism of post-prandial lipoproteins and plasma levels of Lp(a). Eight normolipidemic, male runners who ran 30–40 miles/week were studied in the trained state and after 14–22 days of detraining. Two of the subjects were studied in the reverse order to control for any confounding effects of exercise sequence. Detraining resulted in (1) a 12% ( P = 0.002) reduction in the subjects' aerobic capacity, (2) a 7.7% ( P = 0.007) reduction in fasting concentrations of high density lipoprotein cholesterol (HDL-C), (3) a 21% ( P = 0.01) reduction in post-heparin lipoprotein lipase activity. Lp(a) concentrations did not change significantly (mean increase 15%, P = 0.076). Fasting plasma concentrations of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) did not change in the detrained state. There was little fluctuation over 24 h in plasma concentrations of TC, LDL-C and HDL-C in either the trained or detrained states. TG concentrations fluctuated over the 24 h in accord with food intake, but there were no exercise-related changes. Exercise had a dramatic effect on chylomicron and chylomicron remnant metabolism as measured by retinyl palmitate measurements. The mean areas under the concentration vs. time curves (AUC) for chylomicron-retinyl esters increased by 41% ( P = 0.013) and for chylomicron remnant-retinyl ester by 37% ( P = 0.058) following detraining. Thus, brief intervals of detraining reduced fasting concentrations of HDL-C and decreased the metabolism of chylomicrons. These changes are associated with an increased incidence of atherosclerosis.

Normal postprandial lipemia in men with low plasma HDL concentrations.

To examine the relation between postprandial lipemia and high density lipoprotein (HDL) concentrations, we measured the plasma triglyceride and retinyl palmitate responses to 50-g fat meals of 1) 25 men with low HDL cholesterol concentrations (less than 36 mg.dl-1) and normal fasting triglyceride concentrations, 2) 25 men with normal HDL cholesterol (greater than 40 mg.dl-1) and normal fasting triglyceride concentrations, and 3) 20 men with mild to moderate fasting hypertriglyceridemia (250-347 mg.dl-1). The average magnitude of postprandial lipemia induced by the fat meals was markedly higher in the hypertriglyceridemic men (593 +/- 311 mg.dl-1.8 hr) than in either of the normolipidemic groups. In normotriglyceridemic men with low HDL cholesterol, mean postprandial lipemia (303 +/- 158 mg.dl-1.8 hr) was similar to the corresponding value of men with normal HDL (283 +/- 130 mg.dl-1.8 hr). Postprandial plasma retinyl palmitate concentrations, which reflect chylomicron remnant metabolism, also were similar in normal-HDL and low-HDL groups. These data suggest that defects in chylomicron-triglyceride clearance that give rise to excess postprandial lipemia are not a common occurrence in normolipidemic men with low HDL cholesterol concentrations. Accordingly, the low HDL cholesterol concentrations measured in the normotriglyceridemic men in this study must be attributable to factors other than an exaggerated postprandial lipemia.