| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| A study on the values computed by dieticians and chemical analysis of fats, cholesterol, and P/S ratio in food Nakamura, T., K. Takebe, et al. (1993), Tohoku J Exp Med 171(4): 319-25. Abstract: Dieticians computed the fat and cholesterol contents of 11 foods that were commercially produced as ready-to-eat food from food component lists and obtained the P/S ratio (polysaturated/saturated fatty acids) from the fatty acid component list. Meanwhile the same foods were diluted and homogenized. The internal standard was combined with hepatadecanoic acid and tricaprin. The samples that had been extracted by the Folch method were analyzed for their lipid content (GC analysis using a HS-SS-10 columns for fatty acids and an OV-1 column for lipid and cholesterol). A significant positive correlation was noted between the results of dieticians' analysis and those obtained from a gas chromatographic analysis of lipid and cholesterol contents and the P/S ratio, proving that lipid analysis of food by dieticians is highly reliable. Therefore for diseases (such as hyperlipemia, arteriosclerosis, obesity, diabetes mellitus, fatty liver, and pancreatitis) in which dietary factors have a significant effect on their clinical course, dietary instructions on dietary fats based on an analysis by dieticians are considered to be effective. |
| A study to determine the response of coronary atherosclerosis to raising low high density lipoprotein cholesterol with a fibric-acid derivative in men after coronary bypass surgery. The rationale, design, and baseline characteristics of the LOCAT Study. Lopid Coronary Angiography Trial Syvanne, M., M. R. Taskinen, et al. (1997), Control Clin Trials 18(1): 93-119. Abstract: Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged < or = 70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2 1/2 years. The lipid inclusion criteria were HDL cholesterol concentration < or = 1.1 mmol/L, low density lipoprotein (LDL) cholesterol < or = 4.5 mmol/L, and serum triglyceride < or = 4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index > 30 kg/m2, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement System, a validated computer-assisted image-analysis and quantitation package. The primary endpoints are the changes in the per-patient mean of 1) the average diameter of evaluable native coronary segments, and 2) the minimal luminal diameter of evaluable stenoses, and 3) the appearance of new lesions. Extensive lipoprotein and other metabolic studies and analyses of genetic polymorphisms are carried out to study the determinants of CAD progression. At baseline, the study subjects were 59.1 +/- 6.8 (mean +/- standard deviation) years old, had a body mass index 26.4 +/- 2.2 kg/m2, and serum triglyceride, serum cholesterol, HDL cholesterol, and LDL cholesterol concentrations 1.64 +/- 0.64, 5.17 +/- 0.64, 0.82 +/- 0.14, and 3.61 +/- 0.53 mmol/L, respectively. |
| A summary of implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines Grundy, S. M., J. I. Cleeman, et al. (2004), Arterioscler Thromb Vasc Biol 24(8): 1329-30. |
| A summary of the science supporting the new National Cholesterol Education Program dietary recommendations: what dietitians should know Van Horn, L. and N. Ernst (2001), J Am Diet Assoc 101(10): 1148-54. |
| A surgical model for studying biliary bile acid and cholesterol metabolism in swine Faidley, T. D., S. T. Galloway, et al. (1991), Lab Anim Sci 41(5): 447-50. Abstract: Techniques were developed in young growing pigs to simultaneously collect and reinfuse bile. Silastic cannulae were designed and surgically implanted in the common bile duct and the duodenum. Direct sampling of the hepatic bile was achieved by bypassing the gallbladder. The techniques allowed for steady-state studies of hepatic function to be conducted in conscious swine in two different studies. Pigs, thus surgically modified, can serve as an appropriate model for physiologic, pharmacologic, and nutritional research that involves bile sampling. |
| A survey of dietetics professionals' knowledge of and attitudes toward cholesterol management Underbakke, G., M. B. Plane, et al. (1993), J Am Diet Assoc 93(3): 301-4. Abstract: Dietetics professionals in Wisconsin (n = 687) were surveyed to assess their knowledge, attitudes, practices, experience, and educational interests regarding cholesterol management. The survey, conducted to guide the development of cholesterol education programming in the state, found that most dietetics professionals are familiar with and support the guidelines of the National Cholesterol Education Program (NCEP). Ninety-three percent of dietetics professionals responding to the survey believe that reducing serum cholesterol levels will reduce the risk of heart disease; the same percentage of respondents were familiar with NCEP guidelines for detecting and treating blood cholesterol levels and knew which cholesterol levels should be treated. Seventy-three percent were familiar with the American Heart Association step 1 diet, and 69% were familiar with the step 2 diet. On average, survey respondents defined a cholesterol level of 6.12 mmol/L as "high risk"; this value is almost identical to the NCEP definition. Respondents were optimistic about patients' ability to reduce their blood cholesterol levels through dietary modifications. Dietetics professionals are interested in education on cholesterol management, although individual educational interests vary depending on the respondent's area of practice. |
| A synergistic effect between cholesterol and tryptophan-flanked transmembrane helices modulates membrane curvature van Duyl, B. Y., H. Meeldijk, et al. (2005), Biochemistry 44(11): 4526-32. Abstract: The aim of this study was to gain insight into the structural consequences of hydrophobic mismatch for membrane proteins in lipid bilayers that contain cholesterol. For this purpose, tryptophan-flanked peptides, designed to mimic transmembrane segments of membrane proteins, were incorporated in model membranes of unsaturated phosphatidylcholine bilayers of varying thickness and containing varying amounts of cholesterol. Analysis of the lipid organization by (31)P NMR and cryo-TEM demonstrated the formation of an isotropic phase, most likely representing a cubic phase, which occurred exclusively in mixtures containing lipids with relatively long acyl chains. Formation of this phase was inhibited by incorporation of lysophosphatidylcholine. These results indicate that the isotropic phase is formed as a consequence of negative hydrophobic mismatch and that its formation is related to a negative membrane curvature. When either peptide or cholesterol was omitted from the mixture, isotropic-phase formation did not occur, not even when the concentrations of these compounds were significantly increased. This suggests that formation of the isotropic phase is the result of a synergistic effect between the peptides and cholesterol. Interestingly, isotropic-phase formation was not observed when the tryptophans in the peptide were replaced by either lysines or histidines. We propose a model for the mechanism of this synergistic effect, in which its dependence on the flanking residues is explained by preferential interactions between cholesterol and tryptophan residues. |
| A target for cholesterol absorption inhibitors in the enterocyte brush border membrane Detmers, P. A., S. Patel, et al. (2000), Biochim Biophys Acta 1486(2-3): 243-52. Abstract: Uptake of cholesterol by the intestinal absorptive epithelium can be selectively blocked by specific small molecules, like the sterol glycoside, L-166,143. Furthermore, (3)H-labeled L-166,143 administered orally to hamsters binds specifically to the intestinal mucosa, suggesting the existence of a cholesterol transporter. Using autoradiography, the binding site of (3)H-L-166,143 in the hamster small intestine was localized to the very apical aspect of the absorptive epithelial cells. Label was competed by non-radioactive L-166,143 and two structurally distinct cholesterol absorption inhibitors, suggesting a common site of action for these compounds. L-166,143 blocked uptake of (3)H-cholesterol into enterocytes in vivo, as demonstrated by autoradiography, suggesting that it inhibits a very early step of cholesterol absorption, incorporation into the brush border membrane. This conclusion was confirmed by studies in which intestinal brush borders were isolated from hamsters dosed with (3)H-cholesterol in the presence or absence of L-166,143. Uptake of (3)H-cholesterol into the membranes was substantially inhibited by the compound. In contrast, an inhibitor of acyl CoA:cholesterol acyltransferase, did not affect uptake of (3)H-cholesterol into the brush border membranes. These results strongly support the existence of a specific transporter that facilitates the movement of cholesterol from bile acid micelles into the brush border membranes of enterocytes. |
| A test of the John Henryism hypothesis: cholesterol and blood pressure Wiist, W. H. and J. M. Flack (1992), J Behav Med 15(1): 15-29. Abstract: The personality predisposition "John Henryism" (JH) is a self-perception that one can meet demands of the environment through hard work and determination. The JH scale measures "efficacy of mental and physical vigor, commitment to hard work, and determination to reach one's goals." Previous research found an increased prevalence of hypertension among African-Americans with high JH scores and low socioeconomic status (SES). Six hundred fifty-three adult African-Americans in a church-based cardiovascular risk factor screening program completed the JH questionnaire. The prevalence of cholesterol greater than or equal to 240 mg/dl was highest (27%) among the high-JH/low-SES group when adjusted for age, sex, and body mass index. High JH/low SES was not associated with a greater prevalence of high blood pressure. Findings of this study suggest the need for additional research on John Henryism, socioeconomic factors, and cardiovascular risk among randomly selected samples of geographically and economically diverse African-Americans. |
| A thermodynamic analysis of the partitioning of cholesterol and related compounds between trioleoylglycerol and egg phosphatidylcholine bilayers Sandermann, H., Jr., G. H. Addona, et al. (1997), Biochim Biophys Acta 1346(2): 158-62. Abstract: The free energy of transfer of a number of alcohols, including cholesterol, from a bulk isotropic lipid phase, trioleoylglycerol (TG), to an anisotropic lipid phase, egg phosphatidylcholine (PC), was determined. n-Alkane-1-ols partitioned preferentially into the bilayer phase; for example, the free energy of transfer of octanol-1 from TG to PC was about -1.0 kcal/mol. This preference declined with increasing number of carbons at a rate of 40 cal/mol of CH2. Cholesterol had a much stronger preference for the bilayer with a free energy of -1.3 kcal/mol, compared to an extrapolated value of -0.2 kcal/mol for a normal alkane-1-ol with the same number of carbon atoms. Thus, the excess free energy of -1.1 kcal/mol represents the favourable interaction of the cholesterol skeleton with the bilayer phase. This conclusion was confirmed by comparing cholesterol 3-hemisuccinate to oleic acid. Substituting TG for water as the standard state has eliminated the large hydrophobic effect and has permitted us to identify for the first time the subtle binding increment of the steroid ring system. |
| A thermodynamic model for extended complexes of cholesterol and phospholipid Anderson, T. G. and H. M. McConnell (2002), Biophys J 83(4): 2039-52. Abstract: Studies of monolayer mixtures of certain phospholipids with cholesterol by epifluorescence microscopy and measurement of cholesterol desorption show evidence for the formation of "condensed complexes." A thermodynamic model of these complexes has been developed and has been shown to be generally consistent with observed phase diagrams, cholesterol desorption rates, and electric field susceptibility. Previous work has shown that complexes comprising 10-50 molecules provide good agreement with experimental results. The present study examines the calculated properties of complexes containing very large numbers of molecules and extends the condensed complex model to incorporate the formation of complexes of variable size. Trends in equilibrium composition are similar to those calculated for small complexes. Thermal transitions are continuous, with a strong composition dependence of the breadth of the transition. The average number of molecules in a large complex shows a pronounced dependence on the composition of the reaction mixture. Large complexes have properties of a separate thermodynamic phase. |
| A thermodynamic study of the effects of cholesterol on the interaction between liposomes and ethanol Trandum, C., P. Westh, et al. (2000), Biophys J 78(5): 2486-92. Abstract: The association of ethanol with unilamellar dimyristoyl phosphatidylcholine (DMPC) liposomes of varying cholesterol content has been investigated by isothermal titration calorimetry over a wide temperature range (8-45 degrees C). The calorimetric data show that the interaction of ethanol with the lipid membranes is endothermic and strongly dependent on the phase behavior of the mixed lipid bilayer, specifically whether the lipid bilayer is in the solid ordered (so), liquid disordered (ld), or liquid ordered (lo) phase. In the low concentration regime (<10 mol%), cholesterol enhances the affinity of ethanol for the lipid bilayer compared to pure DMPC bilayers, whereas higher levels of cholesterol (>10 mol%) reduce affinity of ethanol for the lipid bilayer. Moreover, the experimental data reveal that the affinity of ethanol for the DMPC bilayers containing small amounts of cholesterol is enhanced in the region around the main phase transition. The results suggest the existence of a close relationship between the physical structure of the lipid bilayer and the association of ethanol with the bilayer. In particular, the existence of dynamically coexisting domains of gel and fluid lipids in the transition temperature region may play an important role for association of ethanol with the lipid bilayers. Finally, the relation between cholesterol content and the affinity of ethanol for the lipid bilayer provides some support for the in vivo observation that cholesterol acts as a natural antagonist against alcohol intoxication. |
| A trypsin-sensitive protein is required for utilization of exogenous cholesterol for pregnenolone synthesis by placental mitochondria Espinosa-Garcia, M. T., J. F. Strauss, 3rd, et al. (2000), Placenta 21(7): 654-60. Abstract: The utilization of cholesterol for steroid hormone synthesis by human placental mitochondria is poorly understood. The human placenta does not express the steroidogenic acute regulator protein, which is critical for cholesterol delivery to the cholesterol side chain cleavage system in adrenal and gonadal mitochondria. We explored the mechanism underlying cholesterol transport in human placental mitochondria by measuring its transformation into pregnenolone. Mitochondria of syncytiotrophoblast from human term placenta were isolated by centrifugation through a sucrose gradient. The synthesis of pregnenolone in the presence of exogenous cholesterol was increased two-fold in syncytiotrophoblast mitochondria. Treatment of mitochondria with trypsin prevented the increase in the synthesis of pregnenolone in the presence of exogenous cholesterol. However, when 22-OH cholesterol, a substrate that readily crosses membranes, was added, the trypsin-treated mitochondria synthesized increased amounts of pregnenolone. The trypsin-treated mitochondria were intact, since oxygen consumption, succinate dehydrogenase and the adenine nucleotide translocase activities were not significantly different from in untreated mitochondria. However, activity of NADH cytochrome c oxidoreductase, an outer mitochondrial membrane enzyme, was reduced in the trypsin-treated mitochondria, reflecting the selective degradation of proteins. In addition, SDS-PAGE analysis revealed the loss of a prominent 34 kDa band which proved to be a novel porin-like protein that binds to cholesterol. These results support our previous assumption that human placental mitochondria employ a novel protein(s)-mediated the mechanism to take up cholesterol for steroidogenesis. |
| A two-step mechanism for free cholesterol and phospholipid efflux from human vascular cells to apolipoprotein A-1 Fielding, P. E., K. Nagao, et al. (2000), Biochemistry 39(46): 14113-20. Abstract: Smooth muscle and endothelial cells in vivo are quiescent yet exposed to high levels of lipoprotein lipids. Phospholipid (PL) and free cholesterol (FC) efflux maintain homeostasis. Smooth muscle cells (SMC) expressed high levels of ABC-1 transporter mRNA, and glyburide-dependent PL and FC efflux to apolipoprotein A-1 (apo A-1), the major protein of high-density lipoprotein. FC efflux was inhibited by vanadate and okadaic acid, while PL efflux was not. Phosphatidylcholine was the major PL transferred by both cell types. Stimulation of phosphatidylserine efflux, redistributed within the membrane by this transporter, was only minimally increased. Umbilical vein and aortic endothelial cells expressed little ABC-1 mRNA, nor did these cells promote either PL or FC efflux in response to the presence of apo A-1. To investigate the mechanism of ABC-1-dependent lipid efflux from these cells, apo A-1 was preincubated in the presence of unlabeled SMC or fibroblasts, and the conditioned medium was then transferred to endothelial cells. This medium catalyzed the efflux of FC but not of PL from endothelial cells. Such FC efflux was resistant to glyburide but inhibited by okadaic acid and vanadate. The data suggest that ABC-1-dependent PL efflux precedes FC efflux to apo A-1 and that the complex of apo A-1 and PL is a much better acceptor of FC than apo A-1 itself. Inhibition of FC but not PL efflux by vanadate and okadaic acid suggests these transfers involve different mechanisms. |
| A water-extract of the Korean traditional formulation Geiji-Bokryung-Hwan reduces atherosclerosis and hypercholesteremia in cholesterol-fed rabbits Kim, B. J., Y. K. Kim, et al. (2003), Int Immunopharmacol 3(5): 723-34. Abstract: Geiji-Bokryung-Hwan (GBH), a drug preparation consisting of five herbs of Cinnamomi Ramulus (Geiji), Poria Cocos (Bokryun), Mountan Cortex Radicis (Mokdanpi), Paeoniae Radix (Jakyak) and Persicae Semen (Doin), is a traditional Korean herbal medicine that is widely used in the treatment of atherosclerosis-related disorders. A water extract of GBH was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and inhibit low-density lipoprotein (LDL) oxidation more effectively than probucol, a well-known commercially available antioxidant. In order to evaluate the anti-atherogenic potential of this medication, New Zealand White (NZW) rabbits were fed a normal diet for 12 weeks, a high cholesterol diet, a high cholesterol diet containing 1% probucol or a high cholesterol diet containing 5% water-soluble extract of GBH. Both GBH and probucol reduced plasma cholesterol levels. LDLs from the GBH-treated group were more resistant to Cu(2+)-induced oxidation and contained more vitamin E than LDLs from the high cholesterol diet group. Endothelial damage, determined at week 6, was reduced by 55% in the GBH group (P<0.01). GBH treatment reduced an atherosclerotic area in the abdominal aorta by 58% (P<0.05) and cholesterol deposition in the thoracic aorta by 55% (P<0.05). The severity of atherosclerosis in the GBH group was significantly reduced after an adjustment using cholesterol exposure as an index of the cholesterol-lowering effect. On the other hand, diet-induced hyperlipidemic rabbits were given water extract of GBH in doses of 50 (Group B) and 200 mg/kg (Group C) and compared with controls (Group A). At 40 days after intervention in groups A, B and C, total and LDL cholesterol levels were significantly lowered (P<0.01). LDL/high density lipoprotein (HDL) ratio was also significantly decreased (P<0.01). This study concludes that the reduction in atherosclerosis by GBH relies not only on its cholesterol-lowering effect but also more heavily on its antioxidant potential, which prevents endothelial damage and inhibits LDL oxidative modification in hypercholesterolemic animals. |
| A weight reduction intervention that optimizes use of practitioner's time, lowers glucose level, and raises HDL cholesterol level in older adults Wylie-Rosett, J., C. Swencionis, et al. (1994), J Am Diet Assoc 94(1): 37-42; quiz 43-4. Abstract: OBJECTIVE: The effects of a cognitive-behavioral weight control intervention were compared in two independent-living, older adult (mean age = 70.5 years) communities. DESIGN: The research design compared the experimental community (n = 163), which received the intervention, with the control community (n = 162). SUBJECTS: Overweight individuals (> 4.5 kg of age-adjusted weight according to height-weight tables) were recruited from both communities. INTERVENTION: Components of the Dietary Intervention: Evaluation of Technology (DIET) program included a video-tape, a workbook, computerized tracking of participants, a telephone hot line, educational group discussions, and individual consultation. OUTCOME MEASURES: Changes in body weight, body mass index, and lipid and glucose measures were selected to evaluate the effectiveness of the intervention. STATISTICAL ANALYSIS: One-way analysis of variance by group was done to compare changes in continuous variables between the intervention and control communities. RESULTS: Baseline body mass index and weight were 30.8 and 79.5 kg, respectively, in the experimental community and 28.8 and 75.8 kg, respectively, in the control community. Mean weight change in the experimental community was -3.2 kg after 40 weeks of intervention, compared with no weight change in the control community (P <.0001). Mean plasma glucose level decreased -0.3 mmol/L and mean high-density lipoprotein cholesterol level increased 0.15 mmol/L in the experimental community, compared with no change in lipid parameter and a +0.3 mmol increase in glucose level in the control community (P <.0001). APPLICATIONS: Our findings suggest that an intervention that optimizes use of the practitioner's time can achieve a moderate weight loss and metabolic improvement in a community of older adults. |
| ABC transporters and cholesterol metabolism Schmitz, G. and W. E. Kaminski (2001), Front Biosci 6: D505-14. Abstract: ATP-binding cassette (ABC) proteins form a group of highly conserved cellular transmembrane transporters. Studies over the past year have implicated ABC transporters in cellular lipid trafficking processes. This notion has recently been confirmed and extended by the finding that the ABC transporter ABCA1 is a key regulator of high-density lipoprotein (HDL) metabolism and macrophage targeting to the RES or the vascular wall. Expression of a large number of ABC transporters in monocytes/macrophages and their regulation by cholesterol flux render these transporter molecules potentially critical players in chronic inflammatory diseases such as atherosclerosis. |
| ABC1 gene expression and ApoA-I-mediated cholesterol efflux are regulated by LXR Schwartz, K., R. M. Lawn, et al. (2000), Biochem Biophys Res Commun 274(3): 794-802. Abstract: ATP-binding cassette transporter 1 (ABC1) mediates the active efflux of cholesterol from cells to apolipoproteins. To study the mechanisms of regulation of ABC1 gene expression, RAW 264.7 macrophages were transiently transfected with ABC1 promoter-luciferase reporter gene-fusion constructs. Transcription from a 1.64 kb fragment was induced by cholesterol loading but was not responsive to cAMP. Treatment of the cells with 9-cis retinoic acid or 20(S)-hydroxycholesterol, ligands for the nuclear receptors LXR and RXR, resulted in a marked induction of luciferase expression. The responsible control element was mapped to an imperfect direct repeat of the nuclear receptor half-site TGACCT separated by four bases (DR-4) that binds LXR/RXR heterodimers. Endogenous ABC1 gene expression in RAW cells and apolipoprotein A-I mediated cholesterol efflux were also upregulated by both receptor ligands. These findings raise the possibility that ligands that activate the LXR-RXR heterodimer may be useful for the therapeutic modulation of the ABC1 pathway. |
| ABCA1 and amphipathic apolipoproteins form high-affinity molecular complexes required for cholesterol efflux Fitzgerald, M. L., A. L. Morris, et al. (2004), J Lipid Res 45(2): 287-94. Abstract: Apolipoproteins, such as apolipoprotein A-I (apoA-I), can stimulate cholesterol efflux from cells expressing the ATP binding cassette transporter A1 (ABCA1). The nature of the molecular interaction between these cholesterol acceptors and ABCA1 is controversial, and models suggesting a direct protein-protein interaction or indirect association have been proposed. To explore this issue, we performed competition binding and chemical cross-linking assays using six amphipathic plasma proteins and an 18 amino acid amphipathic helical peptide. All seven proteins stimulated lipid efflux and inhibited the cross-linking of apoA-I to ABCA1. Cross-linking of apoA-I to ABCA1 was saturable and occurred at high affinity (Kd of 7.0 +/- 1.9 nM), as was cross-linking of apoA-II. After binding to ABCA1, apoA-I rapidly dissociated (half-life of 25 min) from the complex and was released back into the medium. A mutant form of ABCA1 (W590S) that avidly binds apoA-I but fails to promote cholesterol efflux released apoA-I with similar kinetics but without transfer of cholesterol to apoA-I. Thus, a high-affinity, saturable, protein-protein interaction occurs between ABCA1 and all of its amphipathic protein ligands. Dissociation of the complex leads to the cellular release of cholesterol and the apolipoprotein. However, dissociation is not dependent on cholesterol transfer, which is a clearly separable event, distinguishable by ABCA1 mutants. |
| ABCA1 is essential for efficient basolateral cholesterol efflux during the absorption of dietary cholesterol in chickens Mulligan, J. D., M. T. Flowers, et al. (2003), J Biol Chem 278(15): 13356-66. Abstract: The ATP-binding cassette transporter A1 (ABCA1) participates in the efflux of cholesterol from cells. It remains unclear whether ABCA1 functions to efflux cholesterol across the basolateral or apical membrane of the intestine. We used a chicken model of ABCA1 dysfunction, the Wisconsin hypoalpha mutant (WHAM) chicken, to address this issue. After an oral gavage of radioactive cholesterol, the percentage appearing in the bloodstream was reduced by 79% in the WHAM chicken along with a 97% reduction in the amount of tracer in high density lipoprotein. In contrast, the percentage of radioactive cholesterol absorbed from the lumen into the intestine was not affected by the ABCA1 mutation. Liver X receptor (LXR) agonists have been inferred to decrease cholesterol absorption through activation of ABCA1 expression. However, the LXR agonist T0901317 decreased cholesterol absorption equally in both wild type and WHAM chickens, indicating that the effect of LXR activation on cholesterol absorption is independent of ABCA1. The ABCA1 mutation resulted in accumulation of radioactive cholesterol ester in the intestine and the liver of the WHAM chicken (5.0- and 4.4-fold, respectively), whereas biliary lipid concentrations were unaltered by the WHAM mutation. In summary, ABCA1 regulates the efflux of cholesterol from the basolateral but not apical membrane in the intestine and the liver. |