| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Separation and quantification of cholesterol and major phospholipid classes in human semen by high-performance liquid chromatography and light-scattering detection Grizard, G., B. Sion, et al. (2000), J Chromatogr B Biomed Sci Appl 740(1): 101-7. Abstract: A high-performance liquid chromatographic method coupled with light-scattering detection for the separate and accurate quantification of cholesterol and main phospholipid classes was applied to human spermatozoa and seminal plasma (SP). This method is based on normal-phase chromatography with silica gel as stationary phase and a ternary gradient with hexane, mixtures of chloroform-methanol and water as mobile phase. Lipids are separated with a good resolution and a high reproducibility. About 5 x 10(6) spermatozoa or 25 microl of seminal plasma are sufficient to accurate quantitative analysis of phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidycholine (PC), sphingomyelin (SM) and cholesterol. PC is the predominant phospholipid class in spermatozoa (102+/-8 nmol/10(8) spermatozoa) whereas SM is the major in the SP (163+/-6 nmol/ml). Both in spermatozoa and SP, PI is the minor class of the phospholipids (12+/-1 nmol/10(8) spermatozoa and 24+/-2 nmol/ml). In conclusion, this method offers interesting perspectives for analysis of sperm lipid composition in semen samples with low quantities of spermatozoa. |
| Separation and quantitation of cholesterol "carriers" in bile Donovan, J. M. and M. C. Carey (1990), Hepatology 12(3 Pt 2): 94S-104S; discussion 104S-105S. Abstract: On the basis of phase equilibria theory and experimental data, we discuss the identity, separation and quantitation of cholesterol-solubilizing lipid aggregates in bile, trivially known as cholesterol "carriers." We first describe analogies (as well as lack of correspondence) between equilibrium phase diagrams of aqueous bile salt, lecithin and cholesterol systems and phase equilibria in native biles. At equilibrium, the possible number and types of different cholesterol "carriers" are limited by constraints placed by the phase rule. These "carriers" include simple micelles (bile salts without lecithin), mixed micelles (bile salts plus lecithin), a lecithin plus cholesterol lamellar phase composed of single bilayer structures (vesicles) or multilamellar structures (liquid crystals) and possibly fragments of a hexagonal phase. Clearly, in this context, cholesterol monohydrate crystals, no matter how small, cannot be considered "carriers." We also use a metastable "phase diagram" for aqueous taurocholate-egg yolk lecithin-cholesterol systems to interpret physicochemical studies on the formation and stability of native biles. In biliary lipid systems, bile salt monomers with or without simple bile salt micelles are present in the aqueous "phase" in equilibrium with mixed micelles/or vesicles. This bile salt concentration is designated the intermicellar concentration but actually represents the total nonmixed micellar/nonvesicular concentration of bile salts (i.e., bile salt monomers and simple bile salt micelles when present) and may be a value that falls below, equal to or above the critical micellar concentration of the bile salts. Experimental estimates of the intermicellar-intervesicular bile salt concentration in model systems are compared with the range of bile salt concentrations that has been used in the literature to separate the presently accepted cholesterol "carriers" (mixed micelles and vesicles) in both model and native biles. We also reinterpret published lipid compositions of phases separated from human bile, using both a nonequilibrium "phase diagram" and an equilibrium phase diagram for the model system, taurocholate-egg yolk lecithin-cholesterol. From these analyses, we conclude that precise quantitation of cholesterol "carriers" in bile awaits methods to accurately determine the intermicellar-intervesicular concentration of bile salts in any individual bile, as well as advances in nonperturbing separatory procedures, and methods to control the thermal and temporal history of native bile samples. |
| Separation and quantitation of cholesterol carriers in native bile by ultracentrifugation Amigo, L., C. Covarrubias, et al. (1990), Hepatology 12(3 Pt 2): 130S-133S. Abstract: The vesicular and micellar carriers of biliary cholesterol were isolated and quantitated from native bile by a simple and short isopyknic ultracentrifugal method. The method was designed to decrease the potential pitfalls of classic ultracentrifugation: osmotic effects of the centrifugation media and hydrostatic pressure effects generated in the centrifuge tube. This was accomplished by using metrizamide as an inert centrifugation medium for isopyknic separation and a vertical rotor. The buoyant density of vesicles isolated from human native bile varied between 1.010 and 1.030 gm/ml, as determined in preformed bile-metrizamide density gradients after 285 min of centrifugation. When 16% metrizamide was directly dissolved in bile, its density increased to 1.060 gm/ml. After 120 min of centrifugation, it was found that more than 95% of total vesicular cholesterol floated at the top of the centrifuge tube. This fraction appeared as one or two white opalescent bands. The present ultracentrifugal method was validated by gel filtration chromatography. It was found that more than 95% of vesicular cholesterol migrated to the top 0.4 ml of the centrifuge tube after the short-run centrifugation. Approximately 5% of total biliary cholesterol present in the vesicular fractions was in fact solubilized in mixed micelles as assessed by gel filtration chromatography. Although the proportion of vesicles and micelles estimated with the present ultracentrifugal method is in the range reported by other authors using the more common chromatographic method, we believe that our method has two major advantages. First, it eliminates the dilutional effect of buffers necessary for gel filtration chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Separation of benzodiazepines using cholesterol-modified fused-silica capillaries in capillary electrochromatography Catabay, A. P., H. Sawada, et al. (1998), J Capillary Electrophor 5(1-2): 89-95. Abstract: This paper describes the use of cholesteryl-10-undecenoate as a capillary column modifier for capillary electrochromatography. This bonded phase has shown an entirely different selectivity as compared to octadecyl silica (ODS) phases in reversed-phase liquid chromatography, specifically in the analysis of the benzodiazepines. This difference serves as the basis for the continuing study as well as the present focus on electrochromatography as a relatively new separation technique. To significantly increase the surface area, etching of the inner wall of a 75-micron capillary is performed using ammonium hydrogen difluoride and is then subsequently modified via a silation reaction with triethoxysilane and subjected to hydrosilation with cholesteryl-10-undecenoate to form the bonded phase. The performance of this capillary is compared with unetched cholesterol-modified and bare, fused-silica capillaries. Efficient resolution was noted for the etched capillary showing the effectiveness of the etching process as well as the selective property of the bonded phase. |
| Separation of cholesterol esters by silver ion chromatography using high-performance liquid chromatography or solid-phase extraction columns packed with a bonded sulphonic acid phase Hoving, E. B., F. A. Muskiet, et al. (1991), J Chromatogr 565(1-2): 103-10. Abstract: Two methods for the separation of cholesterol esters, based on the number of double bonds in their fatty acid moieties, are presented. Silver ion chromatography, usually performed on thin-layer chromatographic plates, was made suitable for high-performance liquid chromatography (HPLC) and solid-phase extraction. Separation on a bonded sulphonic acid phase loaded with silver ions was achieved with cholesterol esters containing up to six double bonds in their fatty acid moieties. No cross-contamination between fractions with different numbers of double bonds was detected with the HPLC method, was demonstrated by subsequent gas chromatographic analysis of the fatty acid moieties, following transmethylation. For adequate separations with the solid-phase extraction columns it proved important to avoid overloading. The methods may be of use for the off-line analyses of the sterol compositions of the isolated fractions, which each contain sterol esters with an equal number of double bonds in their fatty acid moieties. |
| Separation of immunomodulatory and cholesterol-lowering activities of heterocyclic azaspiranes Albrightson, C. R., P. J. Bugelski, et al. (1995), J Pharmacol Exp Ther 272(2): 689-98. Abstract: Azaspiranes are novel immunomodulators which are effective in a variety of autoimmune diseases. One azaspirane analog, SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro 4.5 decane-2-propanamine dihydrochloride), caused a decrease in total serum cholesterol in dogs after oral administration. To determine whether an effect on cholesterol was common to this class of compounds, the immunomodulatory activity was compared with the cholesterol-lowering activity of six azaspirane analogs. The compounds were given to beagles at a dose of 1 mg/kg p.o. for 28 days, and the effect on serum cholesterol was determined. The results from this study showed a clear dissociation between the immunomodulatory and hypocholesterolemic activities of these compounds. Studies performed to determine the mechanism of the decrease in serum cholesterol caused by SK&F 105685 indicated that it was not due to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase or acyl-CoA:cholesterol acyltransferase activities, or to a potentiation of cholesterol-7 alpha-hydroxylase activity. In addition, analysis by gas chromatography of the nonsaponifiable sterol fraction in dog plasma after treatment with SK&F 105685 or SK&F 106333 showed a decrease in cholesterol and an accumulation of lathosterol and an unknown sterol, indicating that the conversion of these sterols is inhibited and cholesterol synthesis is blocked at these steps. SK&F 105685 affected the sterol profile in human hepatoblastoma cells (Hep G2) in a similar way. Characterization of the unknown sterol by gas chromatography and mass spectrometry indicated that the unknown sterol is very similar to cholesterol and lathosterol, but its identity has yet to be established. These results show that the hypocholesterolemic effects of azaspiranes are related to inhibition of one or more of the final steps in the biosynthetic pathway of cholesterol. |
| Separation of lipoproteins by capillary isotachophoresis combined with enzymatic derivatization of cholesterol and triglycerides Zorn, U., C. F. Wolf, et al. (1999), Electrophoresis 20(7): 1619-26. Abstract: Combining specific enzymatic derivatization of cholesterol or triglycerides with capillary isotachophoresis (CITP), human serum lipoproteins are separated into 14 lipoprotein subfractions, monitored and quantitated by direct capillary UV detection. By comparing the separation patterns of human serum with the patterns of lipoprotein particles isolated by sequential ultracentrifugation it became evident that peaks 1-5 represent lipoproteins of the high density lipoprotein (HDL) fraction, peaks 6-8 embody the very low density lipoprotein (VLDL) fraction and chylomicrons, and peaks 7-14 represent the low density lipoprotein (LDL) fraction. Peaks 7 and 8 were found in the VLDL as well as in the LDL fraction. Using triglyceride-specific staining peaks 6-8 occurred prominently; and with cholesterol-specific staining, peaks 1-5 and 7-14 were prominent. The coefficient of variation, for the sum of the peak heights of a pooled serum, was 3.94 for triglyceride-specific staining and 2.32 for cholesterol-specific staining. A linearity range between 0.23 and 2.29 mM/L was found for triglyceride-specific staining and between 0.043 and 4.33 mM/L for cholesterol-specific staining. The practicability of the method was evaluated (i) using blood of humans before and 45 min after an oral fat load. Triglyceride-specific staining revealed a prominent increase in the VLDL fraction and chylomicrones containing peaks 6 and 7, and a minor increase in the HDL fraction containing peaks 3 and 4, and (ii) in patients with manifest hypothyroidism before and after thyroxine therapy. Cholesterol-specific staining demonstrated a massive decrease in the first peak of the HDL fraction and in peaks 9 and 11 of the LDL fraction regarding the hypo versus hyperthyroid state. |
| Separation of liquid phases in giant vesicles of ternary mixtures of phospholipids and cholesterol Veatch, S. L. and S. L. Keller (2003), Biophys J 85(5): 3074-83. Abstract: We use fluorescence microscopy to directly observe liquid phases in giant unilamellar vesicles. We find that a long list of ternary mixtures of high melting temperature (saturated) lipids, low melting temperature (usually unsaturated) lipids, and cholesterol produce liquid domains. For one model mixture in particular, DPPC/DOPC/Chol, we have mapped phase boundaries for the full ternary system. For this mixture we observe two coexisting liquid phases over a wide range of lipid composition and temperature, with one phase rich in the unsaturated lipid and the other rich in the saturated lipid and cholesterol. We find a simple relationship between chain melting temperature and miscibility transition temperature that holds for both phosphatidylcholine and sphingomyelin lipids. We experimentally cross miscibility boundaries both by changing temperature and by the depletion of cholesterol with beta-cyclodextrin. Liquid domains in vesicles exhibit interesting behavior: they collide and coalesce, can finger into stripes, and can bulge out of the vesicle. To date, we have not observed macroscopic separation of liquid phases in only binary lipid mixtures. |
| Separation of micelles and vesicles within lumenal aspirates from healthy humans: solubilization of cholesterol after a meal Yao, L., J. E. Heubi, et al. (2002), J Lipid Res 43(4): 654-60. Abstract: Understanding the physico-chemical relationship of lumenal lipids to one another is critical when elucidating the mechanism of components known to impact cholesterol absorption. Presently, there are no studies that describe the proportion of cholesterol carried as micelles or vesicles within human lumenal contents. Part of the reason for the scarceness of data is because of the lack of appropriate methodology required for reproducible sample collection and analysis. Thus, the object of the present studies was to develop a method to measure the amount of cholesterol carried as micelles or vesicles in human lumenal samples. The method includes the collection of lumenal samples from the ligament of Trietz through a Fredrick Miller tube, separation of the aqueous subphase from the nondigested lipids, separation of micelles and vesicles on Sepharose 4B columns within 48 h of collection using elution buffers consisting of the intermicellar bile acid composition, and finally quantitation of cholesterol eluted off of the columns.The distribution of cholesterol between micelles and vesicles obtained under different concentrations of bile acids and various lipids was comparable to results obtained from phase diagrams using the lumenal molar percentages of lipids obtained from the same samples. |
| Sepsis syndrome stimulates proximal tubule cholesterol synthesis and suppresses the SR-B1 cholesterol transporter Zager, R. A., A. C. Johnson, et al. (2003), Kidney Int 63(1): 123-33. Abstract: BACKGROUND: Previous studies demonstrate that renal cortical/proximal tubule cholesterol accumulation is part of the renal "stress response." The present study was performed to help define underlying mechanisms, using experimental sepsis as a test model. METHODS: Male CD-1 mice and female low-density lipoprotein receptor (LDLR) knockout mice were injected with a heat-killed Escherichia coli suspension. Renal cortex and serum were obtained from these and control mice either 4, 6, or 18 hours later. Tissues samples were assayed for free cholesterol (FC), cholesteryl esters (CE), HMG CoA reductase (HMGCR) mRNA, and SR-B1 the high-density lipoprotein (HDL) receptor/cholesterol transporter. Statin effects on renal cortical HMGCR mRNA and FC/CE levels also were assessed. Finally, the impact of serum from septic versus normal mice on cultured proximal tubule (HK-2) cell cholesterol levels was assessed. RESULTS: Sepsis induced approximately 30% and 300 to 500% increases in renal FC and CE content, respectively. Cholesterol accumulation was not blunted in LDLR-/- mice versus their controls. Statin therapy also did not alter sepsis-induced renal FC/CE accumulation. However, statin treatment exerted no discernible intra-renal activity (for example, no rise in renal HMGCR mRNA), despite significant extra-renal activity (25% reduction in serum cholesterol; 400% increase in hepatic HMGCR mRNA). HK-2 cells exposed to septic serum sustained a 40% cholesterol increase, compared to cells exposed to control serum. This response was completely statin inhibited, proving that de novo synthesis was involved. Sepsis markedly suppressed renal levels of SR-B1 (an FC efflux protein). Renal HMGCR mRNA did not fall despite sepsis triggered cholesterol loading, indicating a failure of negative feedback activity. CONCLUSIONS: Sepsis-induced renal cholesterol accumulation is not simply an intrinsic renal response, since it can be enhanced by circulating "stress factors" that drive HMGCR activity. Sepsis also down-regulates SR-B1. Thus, decreased cell FC efflux, coupled with increased synthesis, may synergistically induce the post-sepsis cholesterol overload state. |
| Sequential estrogen-progestin replacement therapy in healthy postmenopausal women: effects on cholesterol efflux capacity and key proteins regulating high-density lipoprotein levels Ulloa, N., E. Arteaga, et al. (2002), Metabolism 51(11): 1410-7. Abstract: Thirty healthy postmenopausal women were randomized into 2 groups that received a sequential combined hormone-replacement therapy (HRT) (n = 18; conjugated equine estrogen 0.625 mg/d for 28 days and 5 mg of medroxyprogesterone acetate during the last 14 days) or placebo (n = 12). Plasma samples were collected before and during treatment (days 0, 15, 43, 71). High-density lipoprotein (HDL) lipid content, lipoprotein (Lp)A-I and LpA-I:LpA-II concentration, lecithin:cholesterol acyl transferase activity (LCAT), phospholipid transfer protein (PLTP) activity, and the plasma capacity to carry out cholesterol efflux from Fu5AH cells were measured. Most significant changes were found within the first 15 days after HRT. After 71 days of HRT, we found an increase in LpA-I lipoparticles (27%) and the following HDL lipids: phospholipids (21%), triglycerides (45%), and free cholesterol (43%), as well as an increase in cholesterol efflux (12.5%). PLTP activity, on the other hand, decreased 21% after 71 days of treatment. No significant changes in LCAT activity, HDL-cholesterol ester or LpA-I:LpA-II particles were found. Positive correlation between cholesterol efflux and the variables LpA-I and HDL-phospholipids were observed. PLTP was negatively correlated with apolipoprotein (apo) A-I, LpA-I, and LpA-I:LpA-II. In summary, our study, performed during 3 hormonal cycles, shows that HRT not only modifies HDL-cholesterol level, but also its lipid composition and HDL lipoparticle distribution. HRT enhances the plasma capacity to carry out cholesterol efflux from the Fu5AH system and decreases the activity of PLTP, a key protein regulating HDL levels. Considering the protocol sampling, these results represent mainly the estrogenic effect of HRT. |
| Sequential microenzymatic assay of cholesterol, triglycerides, and phospholipids in a single aliquot Nanjee, M. N. and N. E. Miller (1996), Clin Chem 42(6 Pt 1): 915-26. Abstract: The assay of multiple analytes in a single aliquot can be advantageous from both measurement and economic standpoints. The objective of this study was to develop a simple and sensitive microenzymatic method for the determination of three biologically important lipids. Triglycerides (as glycerol), phospholipids (as choline), and total cholesterol (as unesterified cholesterol) were assayed, in that order, by sequential addition of sample, reagents, and microbial enzymes directly into a single microtiter plate well, accompanied by continuous monitoring of a common reporter reaction in which hydrogen peroxide is quantified either by colorimetry with 4-aminoantipyrine and 3-hydroxy-2,4,6-triiodobenzoic acid or by ultraviolet fluorometry with p-hydroxyphenylacetic acid. The detection limit of the method is in the subnanomole mass range for all three lipids. Results obtained with either fluorescence or colored endpoints were in excellent agreement with alternative individual chemical and enzymatic procedures. |
| Sequestration of acetylated LDL and cholesterol crystals by human monocyte-derived macrophages Kruth, H. S., S. I. Skarlatos, et al. (1995), J Cell Biol 129(1): 133-45. Abstract: Monocyte-derived macrophages accumulate and process cholesterol in atherosclerotic lesions. Because of the importance of this process, we examined the interaction of cholesterol crystals and acetylated low density lipoprotein (AcLDL) with human monocyte-macrophages in a combined chemical and morphological study. These two forms of cholesterol induced extensive compartmentalization of the macrophage cytoplasm. Unexpectedly, the compartments maintained a physical connection to the extracellular space as demonstrated with ruthenium red staining. The compartments formed through invagination of the top surface of the macrophage plasma membrane. Some cholesterol crystals and AcLDL were sequestered within these surface-connected compartments for up to five days in the case of the crystals and for one day in the case of AcLDL. Pulse-chase studies of fractionated macrophages indicated that 3Hcholesterol redistributed from the surface-connected compartments into lysosomes (where the cholesterol remained unesterified) and into lipid droplets (where the cholesterol was stored as cholesteryl ester). Intracellular uptake and esterification of cholesterol was blocked by cytochalasin D. However, once cholesterol was sequestered in the surface-connected compartments, subsequent esterification of the cholesterol could not be inhibited by cytochalasin D. Apolipoprotein E was localized within the surface-connected compartments by immunogold labeling suggesting a possible function for this protein in the processing of lipid taken up through the sequestration pathway. Removal of microcrystalline cholesterol from the medium resulted in release of most of the accumulated cholesterol microcrystals from the macrophages, as well as disappearance of the surface-connected compartments. Thus, sequestration is a novel endocytic mechanism in which endocytic compartments remain connected to the extracellular space. This differs from phagocytosis where endocytic vacuoles rapidly pinch off from the plasma membrane. Sequestration provides a means for macrophages to remove substances from the extracellular space and later release them. |
| Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males Kuivenhoven, J. A., B. E. Groenemeyer, et al. (1997), Arterioscler Thromb Vasc Biol 17(3): 595-9. Abstract: This report describes the association between a frequent mutation in the lipoprotein lipase (LPL) gene and HDL cholesterol levels. It concerns a previously described defect that predicts a premature truncation of the LPL protein (447stop). We determined the frequency of this mutation in three groups of healthy men with low-, middle-, and upper-decile HDL cholesterol. The number of carriers of the 447stop allele was significantly greater in the high HDL group than in either the groups with normal HDL (P =.017) or low HDL (P <.0001). Additional functional assessment of this mutation did not reveal distinct differences between wild-type LPL and the LPL447stop protein. In conclusion, we have shown that the 447stop mutation is associated with increased HDL cholesterol in healthy Dutch males, although the underlying mechanism remains to be elucidated. Because HDL cholesterol is strongly inversely related with CAD, this genotype might be of potential benefit to its carriers. |
| Serial changes in serum vitamin K1, triglyceride, cholesterol, osteocalcin and 25-hydroxyvitamin D3 in patients after hip replacement for fractured neck of femur or osteoarthritis Roberts, N. B., J. D. Holding, et al. (1996), Eur J Clin Invest 26(1): 24-9. Abstract: Serum vitamin K1 concentrations were measured at presentation (just before surgery) and then at weekly intervals for 3 weeks in two groups of elderly patients requiring either hemiarthroplasty for fractured neck of femur (FON, n = 13) or total hip replacement for osteoarthritis of the hip (OA, n = 16). In comparison with healthy elderly volunteers (n = 25), serum vitamin K1 concentrations were significantly lower in both groups at presentation, and fell significantly within 24 h after surgery to concentrations approaching non-detectable, subsequently returning to pre-operative values within 3 weeks. Serum vitamin K1 tended to be lower in the fracture group both before and after operation, although calculation of a vitamin K1-triglyceride ratio reduced the apparent difference as triglyceride concentrations were lower in the fracture group. Osteocalcin concentrations were similar and fell significantly after operation in both groups, returning to pre-operative levels within 7 days. No differences in the two forms of osteocalcin (carboxylated and undercarboxylated) were observed either before or after operation in either group. 25-Hydroxyvitamin D3 concentrations were not significantly different between the two groups at any time. Vitamin K1 status may be lower than desirable in certain groups of the elderly population, and supplementation should be considered as prophylactic therapy. |
| Serotonin, 5-hydroxyindolylacetic acid and cholesterol content in blood, cerebrospinal fluid and brain areas for differentiation of suicidal from non-suicidal cause of death Walendzik, H., G. Zimmer, et al. (2000), Arch Kriminol 205(5-6): 131-44. Abstract: In the present study serotonin and its metabolite 5-hydroxyindoleacetic acid was investigated in the cerebrospinal fluid and in discrete brain areas of the left and right hemisphere collected from 34 bodies. Sixteen subjects were suicide victims, and 18 were matched as controls. Matching was done for gender, age, sex and cause of death. In suicide victims the concentration of 5-hydroxyindoleacetic acid in cerebrospinal fluid (occipital) was significantly decreased whereas there was no difference comparing the particular results established from the various brain areas. Nevertheless, there was a non-significant trend towards a higher concentration of serotonin in the thalamic area and towards a lower level in samples collected from the mesencephalon in suicide brains. In suicide subjects, the level of 5-hydroxyindoleacetic acid was often found to be increased in the hippocampus and to be decreased in the thalamus. A differentiation between suicide and homicide seems promising only on condition that the distribution of serotonin and metabolite concentrations in various brain areas is considered. The amount of total cholesterol in blood is suggested to be of limited value. |
| Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway Del Puppo, M., M. G. Kienle, et al. (1998), J Lipid Res 39(12): 2477-82. Abstract: Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease. Serum levels of 7alpha-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients (either normocholesterolemic or hypercholesterolemic) with primary biliary cirrhosis and in control subjects. To evaluate cholesterol synthesis, serum levels of lathosterol were measured, and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols. In normocholesterolemic patients with primary biliary cirrhosis, lathosterol was significantly lower than in normocholesterolemic controls (P < 0.05) whereas no difference was found between hypercholesterolemic patients and hypercholesterolemic controls. Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls (P < 0.01). In patients with primary biliary cirrhosis, serum 7alpha-hydroxycholesterol was slightly higher than in controls. 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls (P < 0.05) and a significant linear correlation (r = 0.771; P < 0.001) was found between 27-hydroxycholesterol and cholesterol. In contrast, in patients with primary biliary cirrhosis, high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol. Our data confirm that in patients with primary biliary cirrhosis, cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7alpha-hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients. acids via the acidic pathway. |
| Serum acetate:propionate ratio is related to serum cholesterol in men but not women Wolever, T. M., J. Fernandes, et al. (1996), J Nutr 126(11): 2790-7. Abstract: Acetic and propionic acids, produced by colonic fermentation of unabsorbed carbohydrates, may influence systemic lipid metabolism. To determine whether the ratio of the concentrations of acetate to propionate in peripheral serum of fasting humans was related to serum cholesterol, we studied 62 men age 45 +/- 17 y (mean +/- SD), range 19-74 y; body mass index 25.0 +/- 2.8 kg/m2 and 69 women 43 +/- 18 y, (range, 18-77 y); body mass index 23.0 +/- 3.1 kg/m2 with normal serum lipid concentrations. The concentrations of serum acetate, propionate and butyrate (means +/- SD) were similar in men (98 +/- 33, 3.8 +/- 1.5 and 2.3 +/- 1.5 micromol/L, respectively) and women (92 +/- 38, 3.9 +/- 1.9 and 2.3 +/- 1.6 micromol/L). There were significant positive relationships between the serum acetate:propionate ratio and total cholesterol (r = 0.466, P = 0.0002) and LDL cholesterol (r = 0.384, P = 0.0023) in men, but in women the relationships were not significant (R = 0.174, P = 0.15 and r = 0.135, P = 0.27, respectively). The relationships in men remained significant after adjustment for age and body mass index. These data support the hypothesis that, at least in men, colonic short-chain fatty acids influence systemic lipid metabolism. The relationships among the factors influencing colonic short-chain fatty acid production, the enterohepatic circulation of endogenous estrogens, dietary phytoestrogens and blood lipids in women, however, need further clarification. |
| Serum adiponectin is associated with high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein particle size in young healthy men Kazumi, T., A. Kawaguchi, et al. (2004), Metabolism 53(5): 589-93. Abstract: The chromosomal localization of adiponectin has been found to be mapped to human chromosome 1q21.4-1q23, a region that was identified as a susceptibility locus for familial combined hyperlipidemia and polygenic type 2 diabetes. As these 2 disorders are associated with low high-density lipoprotein (HDL)-cholesterol, high triglycerides, and insulin resistance (IR), we examined the relation of serum adiponectin concentrations to serum lipid and lipoprotein profiles as well as IR in young healthy men. Serum adiponectin levels were positively associated with HDL-cholesterol, apolipoprotein (apo) A1, and low-density lipoprotein (LDL) particle size, and negatively associated with triglycerides and apo B. Negative associations were also found between adiponectin and body mass index (BMI), percent body fat, and IR,as determined by homeostasis model assessment (HOMA). However, after adjustment for BMI, no significant associations were found between adiponectin and LDL particle size and apo B. In a multiple regression analysis including all variables that showed significant univariate associations with adiponectin, associations of adiponectin with HDL-cholesterol (beta = 0.079, P =.0009), percent body fat (beta = -0.165, P =.002), and serum leptin (beta = -0.291, P =.01) were statistically significant. HDL-cholesterol (beta = 0.077, P =.001), percent body fat (beta = -0.078, P =.03), and LDL size (beta = 0.092, P =.03) emerged as significant and independent determinants of adiponectin after HOMA IR, fasting glucose, triglycerides, and systolic blood pressure (BP) were taken into account. Together, these variables explained 19% of adiponectin variability in the 2 models. HOMA IR did not emerge as a determinant of adiponectin in both models. These findings suggest that in young healthy men hypoadiponectinemia is more closely related to adiposity and dyslipidemia than IR. |
| Serum albumin is a significant intermediate in cholesterol transfer between cells and lipoproteins Zhao, Y. and Y. L. Marcel (1996), Biochemistry 35(22): 7174-80. Abstract: The function of albumin in the movement of cholesterol into and out of non-cholesterol-loaded fibroblasts has been investigated. Cholesterol efflux from cholesterol labeled normal human skin fibroblasts to fatty acid-free human serum albumin (HSA) is biphasic with a rapid first phase that plateaus at about 15 min followed by a nearly linear phase up to 90 min, the longest incubation in this study. Saturation of efflux is observed at about 10 mg of albumin/mL. Efflux is specific to albumin since other molecules, such as ovalbumin or gelatin, do not induce efflux. The ability of HSA to induce cellular cholesterol efflux is low compared to reconstituted discoidal lipoprotein A-I (LpA-I). HSA at 2 mg/mL produces a rate of cholesterol efflux similar to that of LpA-I at 45 micrograms of protein/mL; however, these concentrations are within the physiological range for both HSA and apolipoprotein A-I (apoA-I). The efflux to the medium containing both LpA-I and HSA is greater than that to each of them alone but does not show complete additivity, indicating a competition between HSA and LpA-I. The HSA-mediated cholesterol movement is bidirectional as demonstrated by the transfer of cholesterol from HSA-(3H)- cholesterol complexes to fibroblasts; moreover, the HSA-mediated transfer is much faster than that from cholesterol-containing LpA-I (0.8 versus 0.2 pmol (micrograms of cell protein)-1 (90 min)-1. However, the presence of either low-density lipoprotein (LDL) or LpA-I in the incubation medium significantly inhibits the transfer of cholesterol from HSA-(3H)-cholesterol complexes to fibroblasts, thus allowing the bidirectional transfer of cholesterol between HSA and cells to possibly operate as a net efflux. In conclusion, albumin plays a significant role in cholesterol transfer between cells and lipoproteins. |