Amounts Of Sterols Research Articles

Lipophilic extractives from several nonwoody lignocellulosic crops (flax, hemp, sisal, abaca) and their fate during alkaline pulping and TCF/ECF bleaching

The fate of lipophilic extractives from several nonwoody species (flax, hemp, sisal and abaca) used for the manufacturing of cellulose pulps, was studied during soda/anthraquinone (AQ) pulping and totally chorine free (TCF) and elemental chlorine free (ECF) bleaching. With this purpose, the lipophilic extracts from the raw materials and their unbleached and bleached industrial pulps, were analyzed by gas chromatography–mass spectrometry. Aldehydes, hydroxyfatty acids and esterified compounds such as ester waxes, sterol esters and alkylferulates strongly decreased after soda/AQ pulping while alkanes, alcohols, free sterols and sterol glycosides survived the cooking process. Among the lipophilic extractives that remained in the unbleached pulps, some amounts of free sterols were still present in the TCF pulps whereas they were practically absent in the ECF pulps. Sterol glycosides were also removed after both TCF and ECF bleaching. By contrast, saturated fatty acids, fatty alcohols and alkanes were still present in both bleached pulps.

Cholesterol, non-cholesterol sterols and bile acids in paediatric gallstones

Depending on underlying aetiopathogenetic factors human gallstones contain various amounts of cholesterol, non-cholesterol sterols and bile acids, which have remained unexplored in paediatric gallstone patients. To evaluate sterol and bile acids compositions of paediatric gallstones. Study group included 21 consecutively cholecystectomised children. Gas-liquid chromatography was used to quantitate gallstone sterols and bile acids. Results were compared to adult gallstones (n=194). Cholesterol stones (n=9) had higher proportions of cholesterol and lathosterol, but lower those of lanosterol and phytosterols than pigment stones (n=12) (p<0.05 for each). Patients with gallstone cholesterol content over 70% were female. Gallstone cholesterol positively reflected body mass index and, in cholesterol stones-group, age (r=approximately +0.700, p<0.05). Three patients on parenteral nutrition had brown pigment stones consisting of high amounts of campesterol and sitosterol ranging 483-9303 microg/100 mg of stone. Pigment stones had 13-fold higher amount of bile acids than cholesterol stones (p<0.05). Black pigment stones contained approximately 3-fold higher phytosterol proportions, and pigment stones and cholesterol stones had approximately 43% lower proportions of deoxycholic acid than adults (p<0.05). Gallstones in patients on parenteral nutrition are rich in phytosterols. With respect to gallstone sterols, gallstone disease of adolescent girls resembles that of adults. Composition of bile acids in paediatric gallstones is different from adults.

Extractives in bark of different conifer species growing in Pakistan

AbstractThe amount and composition of lipophilic and hydrophilic extractives, including proanthocyanidins, has been analysed as a first screening in the bark of six Pakistani coniferous tree species, namelyPinus wallichiana,Pinus roxburghii,Pinus gerardiana,Abies pindrow,Taxus fuanaandCedrus deodara. The predominant lipophilic extractives were common fatty and resin acids, fatty alcohols and sterols. In all bark samples, short-chain fatty acids were more abundant than long-chain fatty acids. Generally, the amount of free fatty acids was also larger than the amount of triglycerides. Oleic acid was the most common fatty acid, except inC. deodara, where lignoceric acid dominated. The largest amounts of fatty acids and fatty alcohols were found inP. wallichianaandP. gerardiana.P. gerardianacontained an exceptionally large amount of resin acids, approximately 3% of the bark weight, compared to the other species. The amount of free sterols was approximately at the same level or larger than the amount of steryl esters in most samples. In addition to proanthocyanidins, different known lignans, stilbenes, ferulates and flavonoids were generally predominant amongst the hydrophilic extractives. Resveratrol glycoside was abundant inP. wallichiana, whileC. deodaraandP. gerardianacontained large amounts of lignans and lignan derivatives. All bark extracts contained large amounts of proanthocyanidin-related catechin and its derivatives. Furthermore,C. deodaraandP. roxburghiicontained quite large amounts of taxifolin. In particular,P. wallichianaandA. pindroware potential rich sources of proanthocyanidins, representing approximately 16% and 5% of the bark weight, respectively.

Determination of oxysterols in oxidatively modified low-density lipoprotein by semi-micro high-performance liquid chromatography with electrochemical detection

A simple method for the determination of oxysterols was developed by semi-micro high-performance liquid chromatography with electrochemical detection (semi-micro HPLC–ECD). Semi-micro HPLC–ECD was established using a C30 microbore column, acetonitrile containing 50 mmol/L LiClO 4 as a mobile phase, and an applied potential at +2.8 V versus Ag/AgCl. The current peak height was linearly related to the amount of sterol injected from 12.5 to 250 pmol ( r > 0.999) with a relative standard deviation (RSD) of less than 2.9% ( n = 6). This method was applied to the determination of seven oxysterols in oxidatively modified low-density lipoprotein (Ox–LDL). Oxysterols were determined with a recovery of more than 78.0% and an RSD of less than 2.9% ( n = 6) except for 7-ketocholesterol. 7-Ketocholesterol was determined as a sum of intact 7-ketocholesterol and its degradation product on saponification, cholesta-3,5-dien-7-one, with a recovery of 98.0% and an RSD of 2.5% ( n = 6). From these results, the current method enabled the simultaneous determination of seven oxysterols without any derivatization, providing a useful tool for the assessment of oxysterol contents in Ox–LDL.

Effects of Gibberellic Acid on Primary Terpenoids and Δ9‐Tetrahydrocannabinol in Cannabis sativa at Flowering Stage

Plants synthesize an astonishing diversity of isoprenoids, some of which play essential roles in photosynthesis, respiration, and the regulation of growth and development. Two independent pathways for the biosynthesis of isoprenoid precursors coexist within the plant cell: the cytosolic mevalonic acid (MVA) pathway and the plastidial methylerythritol phosphate (MEP) pathway. However, little is known about the effects of plant hormones on the regulation of these pathways. In the present study we investigated the effect of gibberellic acid (GA(3)) on changes in the amounts of many produced terpenoids and the activity of the key enzymes, 1-deoxy-D-xylulose 5-phosphate synthase (DXS) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), in these pathways. Our results showed GA(3) caused a decrease in DXS activity in both sexes that it was accompanied by a decrease in chlorophylls, carotenoids and Delta(9)-tetrahydrocannabinol (THC) contents and an increase in alpha-tocopherol content. The treated plants with GA(3) showed an increase in HMGR activity. This increase in HMGR activity was followed by accumulation of stigmasterol and beta-sitosterol in male and female plants and campestrol in male plants. The pattern of the changes in the amounts of sterols was exactly similar to the changes in the HMGR activity. These data suggest that GA(3) can probably influence the MEP and MVA pathways oppositely, with stimulatory and inhibitory effects on the produced primary terpenoids in MVA and DXS pathways, respectively.

Chemical composition of lipophilic extractives from jute ( Corchorus capsularis) fibers used for manufacturing of high-quality paper pulps

The chemical composition of the lipophilic extractives from jute ( Corchorus capsularis) fibers, which are used for high-quality paper pulp manufacturing, was thoroughly studied. The extractives content was low (0.4%), and its composition was studied by gas chromatography–mass spectrometry. For a better characterization of the different homologous series and compounds present in minor amounts, the extract was also fractionated by solid-phase extraction. The most predominant lipophilic compounds present in jute fibers were high molecular weight ester waxes (24% of total extract), followed by free fatty acids (17%), free fatty alcohols (17%) and α-hydroxyfatty acids (14%). Additionally, significant amounts of alkanes (6%), ω-hydroxyfatty acids (6%), sterols (6%), steroid and triterpenoid ketones (3%) and steryl glycosides (1%) were also identified, together with minor amounts of mono- and diglycerides.

Co‐crystals of Beeswax and Various Vegetable Waxes with Sterols Studied by X‐ray Diffraction and Differential Scanning Calorimetry

AbstractIn this study, mixtures of purified wax and sterols were melted and subsequently cooled. Using X‐ray diffraction of the mixed, solid phase, it was shown that for up to 30–40 wt% sterols no measurable re‐crystallisation of sterols occurred, i.e. the sterols became dissolved at a molecular level. Probably a form of amorphous co‐crystals of sterols and wax is formed if the molecular ratio does not exceed 1:1. Differential scanning calorimetry (DSC) suggests that a minor amount of pure sterols could already be present at lower sterol levels. This may be because of the higher temperature at which the microstructure is probed when using DSC—melting of the wax might lead to crystallisation of the sterols. For application in foods, the structure as probed by X‐rays at ambient temperatures is more relevant. When sunflower wax and rice bran wax are used, prevention of sterol crystallisation is even more pronounced, probably because the melting temperatures of these waxes are closer to the melting temperature of sterol crystals. Replacing the beeswax with a saturated fat (heRP70), sunflower oil, or jojoba wax (a liquid wax) substantially increases the amount of crystalline sterols. The difference between the various waxes and fats was qualitatively the same for X‐ray diffraction and DSC. Stanols can be incorporated in the same manner and up to similar concentrations. Another insoluble nutritional compound, ursolic acid, has a greater tendency to crystallise in wax. This is probably because the melting temperature of ursolic acid is much higher than that of wax.

Lipid Components of North American Wild Rice (Zizania palustris)

AbstractThe content and composition of fatty acids, sterols, tocopherols, and γ‐oryzanol in wild rice (Zizania palustris) grown in North America were compared with those in regular brown rice (Oryza sativa L.). The lipid content of wild rice ranged from 0.7 to 1.1%, compared with 2.7% in regular brown rice. The lipids of wild rice comprised mainly linoleic (35–37%) and linolenic (20–31%) acids. Other fatty acids included palmitic (14.1–18.4%), stearic (1.1–1.3%), and oleic (12.8–16.2%). Wild rice lipids contained very large amounts of sterols, ranging from 70 g/kg for a Saskatchewan sample to 145 g/kg for Minnesota Naturally Grown Lake and River Rice. The main sterols found in an unsaponified fraction were: campesterol (14–52%), β‐sitosterol (19–33%), Δ5‐avenasterol (5–12%), and cycloartenol (5–12%). Some of sterols, γ‐oryzanols, were present as the phenolic acid esters; the amount ranged from 459 to 730 mg/kg in wild rice lipids. The largest amounts of tocopherols and tocotrienols, 3682 and 9378 mg/kg, were observed in North Western Ontario wild rice samples, whereas the lowest were 251 mg/kg in an Athabasca Alberta sample and 224 mg/kg in regular long‐grain brown rice. The α isomer was the most abundant among tocopherols and tocotrienols. The results of this study showed that wild rice lipids contain large amounts of nutraceuticals with proven positive health effects.

Characterization of Total, Free and Esterified Phytosterols in Tetraploid and Hexaploid Wheats

Dietary plant sterols have received increasing attention in recent years due to their favorable health benefits. The present research focused on quantification of phytosterols as free, esterified and total forms in different tetraploid (5 cultivars of Triticum durum Desf., 9 cultivars of Triticum dicoccon Schrank) and hexaploid (5 cultivars of T. aestivum L., 12 cultivars of Triticum spelta L.) wheats. Tetraploid wheats showed the highest content of total sterol (79.4 and 79.5 mg of sterols /100 g dry weight for T. durum and T. dicoccon, respectively). Hexaploid cultivars were the best source of esterified sterols (40.7% and 37.3% of total sterols for Triticum aestivum and T. spelta, respectively). Significant amounts of free sterols (65.5% and 60.7% of total sterols for T. durum and T. dicoccon, respectively) were found in the tetraploid cultivars. The most abundant phytosterol in all wheat samples was sitosterol accounting for 45.1-59.1, 46.6-57.4 and 38.6-59.5% of total, free and esterified sterol fraction, respectively. These results demonstrate that although the sterol profile present in tetraploid and hexaploid wheat species is the same, differences in their relative amounts and distribution allow statistical differentiation between hexaploids and tetraploids, and between soft and durum wheats.

Effects of seaweed sterols fucosterol And desmosterol on lipid membranes

All eukaryotes universally contain large amounts (20-30%) of higher sterols in their plasma membranes. It remains a mystery why different eukaryotic kingdoms have chosen different higher sterols for their membrane reinforcement, such as cholesterol in animals, ergosterol in fungi, phytosterols in plants, and e.g. desmosterol and fucosterol in algae. We have used a range of biophysical techniques, including calorimetry, fluorescence microscopy, atomic-force microscopy, and vesicle-fluctuation analysis, to assess the various physical effects of fucosterol on lipid membranes.

Central nervous system: cholesterol turnover, brain development and neurodegeneration

The average amount of cholesterol in the whole animal equals approximately 2100 mg/kg body weight, and 15% and 23% of this sterol in the mouse and human, respectively, is found in the central nervous system. There is no detectable uptake across the blood-brain barrier of cholesterol carried in lipoproteins in the plasma, even in the newborn. However, high rates of de novo cholesterol synthesis in the glia and neurons provide the sterol necessary for early brain development. Once a stable brain size is achieved in the adult, cholesterol synthesis continues, albeit at a much lower rate, and this synthesis is just balanced by the excretion of an equal amount of sterol, either as 24(S)-hydroxycholesterol or, presumably, as cholesterol itself.

The linoleic acid influence on molecular interactions in the model of biological membrane

The present work explores the properties for binary (LA/DPPC), (cholesterol/DPPC) and also ternary (LA/cholesterol/DPPC) mixed Langmuir monolayers, at the air–water interface, treated as the simplest models of a half of the biological membranes. In ternary monolayers both cholesterol and DPPC were mixed at constant molar ratios that correspond to the proportions occuring in different natural membranes, among which fibroblast membrane (where the amount of phospholipid predominates) and also erythrocyte membrane (where the amount of sterol predominates) were taken into consideration. Our researches were conducted by using the Langmuir film balance, by means of which we registered the surface pressure ( π) as a function of the area of water surface available to each molecule ( A). It was found that LA and DPPC also cholesterol and DPPC are miscible in binary as well as LA, cholesterol and DPPC in ternary mixed monolayers, however in ternary mixed monolayers, at higher content of fatty acid (for molar fraction X LA = 0.6, 0.8) these components were miscible only at the surface pressure below approximately 27 mN/m. Furthermore the results of our measurements show that LA reveals very strong influence on the membrane composition. Depending on various amounts of this fatty acid within the models of biological membranes it seems to affect different stability of natural bilayer.

Chromatographic Quantitation of Some Bioactive Minor Components in Oils of Wheat Germ and Grape Seeds Produced as By-Products

The objective of this work was to determine some beneficial and bioactive minor lipid components in wheat germ and grape seeds as a result of milling industry of wheat and pressing of grapes in wineries. Sterylglycosides (SG's) were isolated and fractionate into free and acylated SG's by TLC and were determine as their1-anthroylnitriles (1-AN) by HPLC. Moreover, 4-desmethylsterols were isolated, derivatized into their trimethyl silyl derivatives and analyzed by GLC. Tocopherols and tocotrienols were directly analyzed by HPLC. In addition, fatty acids composition by GLC was accomplished. The results were compared to three conventional edible oils, namely, corn, sunflower and cottonseed. It was found that the wheat germ oil (WGO) and grape seed oil (GSO) contained reasonable amounts of whole sterols. Sterylglycosides fraction (SG), which have not been evaluated, it was found that the two by-products contained high amounts of SG's and they were rich in free and acylated campe/stigma SG as well as free and acylated beta-sito SG. Total tocopherols and tocotrienols components were found in very high amounts in WGO (1300 ppm) and GSO (380 ppm). It is noteworthy to mention that GSO contained significant amounts of alpha- and gamma-tocotrienols which prevent cardiovascular diseases and contained reasonable amounts of alpha- and gamma-tocopherols. On the other side, it was found that WG and GS oils were enrich in linoleic acid (omega-6), while linolenic acid (omega-3) was present in higher quantity in WGO.

Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism

BackgroundElevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals.MethodsCholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography – mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p < 0.05; Benjamini Hochberg correction, False Discovery Rate = 0.05). The differential expression of FH associated genes was validated at the mRNA level by qRT-PCR and/or at the protein level by Western Blot or flow cytometry. Functional validation of monocyte scavenger receptor activities were done by binding assays and dose/time dependent uptake analysis using native and oxidized LDL.ResultsUsing microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells.ConclusionOur data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.

Highly sensitive analysis of sterol profiles in human serum by LC-ESI-MS/MS

We have developed a highly sensitive and specific method for the analysis of serum sterol profiles. Sterols in 1 mul of dried serum were derivatized into picolinyl esters (3beta-picolinate) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using the electrospray ionization (ESI) mode. In addition to cholesterol, 19 cholesterol precursors, cholestanol, campesterol, sitosterol, and sitostanol were identified simultaneously. Quantitative analyses for the picolinyl esters of 11 available sterols were performed, and detection limits were found to be less than 1 pg on-column. Reproducibilities and recoveries of 8 noncholesterol sterols were validated according to one-way layout and polynomial equation, respectively. The variances between sample preparations and between measurements by this method were calculated to be 1.6% to 8.2% and 2.5% to 16.5%, respectively. The recovery experiments were performed using 1 mul aliquots of normal human serum spiked with 1 ng to 6 ng of sterols, and recoveries of the sterols ranged from 88.1% to 102.5% with a mean recovery of 98.1%. The present method provides reliable and reproducible results for the identification and quantification of neutral sterols, especially in small volumes of blood samples, which is useful for serological diagnosis of inherited disorders in cholesterol metabolism and for noninvasive evaluation of cholesterol biosynthesis and absorption in humans.

Effect of Parenteral Serum Plant Sterols on Liver Enzymes and Cholesterol Metabolism in a Patient With Short Bowel Syndrome

Hepatobiliary complications are common during parenteral nutrition. Lipid moiety in commercially available solutions contains plant sterols. It is not known whether plant sterols in parenteral nutrition interfere with hepatic function in adults. We detected how different amounts of plant sterols in parenteral nutrition solution affected serum plant sterol concentrations and liver enzymes during a 1.5-year follow-up in a patient with short bowel syndrome. Serum lipid, plant sterol, and liver enzyme levels were measured regularly during the transition from Intralipid (100% soy-based intravenous fat emulsion) to ClinOleic (an olive oil-based intravenous fat emulsion with 80% olive oil, 20% soy oil and lower plant sterols); the lipid supply was also gradually increased from 20 to 35 g/d. Plant sterols in parenteral nutrition solution and serum were measured with gas-liquid chromatography. During infusion of soy-based intravenous fat emulsion (30 g/d, total plant sterols 87 mg/d), the concentrations of sitosterol, campesterol, and stigmasterol were 4361, 1387, and 378 microg/dL, respectively, and serum liver enzyme values were >or= 2.5 times above upper limit of normal. After changing to olive oil-based intravenous fat emulsion (20-35 g/d, plant sterols 37-65 mg/d), concentrations decreased to 2148 to 2251 microg/dL for sitosterol, 569-297 microg/dL for campesterol, and 95-55 microg/dL for stigmasterol. Concomitantly, liver enzyme values decreased to 1.4 to 1.8 times above upper limit of normal at the end of follow-up. The nutrition status of the patient improved. The amount of plant sterols in lipid emulsion affects serum liver enzyme levels more than the amount of lipid.

Lipid and protein utilisation during early development of yellowtail kingfish (Seriola lalandi)

The pelagic yellowtail kingfish Seriola lalandi has become a target species for aquaculture in Asia and Australasia. Australasian production is reliant on larviculture from eggs of captive brood stock; however, knowledge regarding the nutritional requirements of larvae of this species is still scarce, particularly in relation to lipids. As a first step in establishing these requirements, eggs and larvae from captive S. lalandi brood stock were examined for differences in total protein, total lipid and lipid classes between individual spawning events, over the spawning season, and during larval development from fertilisation to 15 days post hatch. Results indicate that total protein egg−1 varied significantly between individual spawning events within a season, but neither total lipid nor total protein egg−1 varied significantly across the spawning season. Brood stock egg lipids were made up of approximately 60% phospholipid, 25% wax and/or sterol esters (WE), 15% triacylglycerol (TAG), and small amounts of sterols and free fatty acids. During the early larval period, both WE and TAG were utilised concurrently for energy. The larvae experienced very high mortality around 5–7 days post hatch, which coincided with very low levels of all neutral lipid classes. Although many other factors may also influence larval mortality, these results indicate that lipid provisioning may be an important factor in larval survival during the critical period around first-feeding in this species. Examination of ratios of TAG:ST, often used as a condition index in fish larvae, suggested that some of the larvae were suffering from starvation. However, as egg-derived WE appears to provide a significant source of energy during the early larval period in S. lalandi, it is suggested that WE should be included in any index of larval nutritional state.

Determination of total sterols in brown algae by Fourier transform infrared spectroscopy

A procedure is proposed for the determination of the total amount of sterols in brown algae Bifurcaria bifurcata, Cladostephus hirsitus, Dictyota dichotoma and Cystoseira sedoides, globally determined as fucosterol, which is the major sterol contained in these algae. The method involves the use of cholesterol as reference standard and a correction factor of 1.259 ± 0.003, which represents the ratio between the slopes of calibration lines obtained from fucosterol and cholesterol. The method provides precise and accurate results for the IR analysis of real samples.

Natural wax constituents of a supercritical fluid CO2 extract from quince (Cydonia oblonga Mill.) pomace

The chemical constituents of a lipophilic extract from quince (Cydonia oblonga Mill.), obtained by supercritical fluid CO(2) extraction of the dried fruit pomace were investigated. Solvent partition of quince wax with n-hexane or acetone yielded an insoluble (crystalline) and a soluble (oily) fraction. Both fractions were analyzed separately using gas chromatography/mass spectrometry (GC/MS). The insoluble fraction consisted of saturated n-aldehydes, n-alcohols and free n-alkanoic acids of carbon chain lengths between 22 and 32, with carbon chain lengths of 26 and 28 dominating. Also odd-numbered unbranched hydrocarbons, mainly C27, C29 and C31, were detected particularly in the acetone-insoluble fraction (total, 15.8%). By means of vacuum liquid chromatography, triterpenoic acids were separated from the hexane-insoluble matter and identified as a mixture of ursolic, oleanolic and betulinic acids. The major constituents of the hexane-soluble fraction were glycerides of linoleic [Δ(9,12), 18:2] and oleic [Δ(9), 18:1] acids, accompanied by free linoleic, oleic and palmitic acids (C16). Moreover β-sitosterol, Δ(5)-avenasterol as well as trace amounts of other sterols were assigned. Finally the carotenoids phytoene and phytofluene were identified and quantified by UV/vis and high-performance liquid chromatography/MS techniques, yielding 1.0 and 0.3% of the quince wax, respectively. It is anticipated that the complex of lipid constituents from quince wax may exert interesting biological activities, the elucidation of which awaits further studies.

Plant Sterols Cause Macrothrombocytopenia in a Mouse Model of Sitosterolemia

Mutations in either ABCG5 or ABCG8 cause sitosterolemia, an inborn error of metabolism characterized by high plasma plant sterol concentrations. Recently, macrothrombocytopenia was described in a number of sitosterolemia patients, linking hematological dysfunction to disturbed sterol metabolism. Here, we demonstrate that macrothrombocytopenia is an intrinsic feature of murine sitosterolemia. Abcg5-deficient (Abcg5(-/-)) mice showed a 68% reduction in platelet count, and platelets were enlarged compared with wild-type controls. Macrothrombocytopenia was not due to decreased numbers of megakaryocytes or their progenitors, but defective megakaryocyte development with deterioration of the demarcation membrane system was evident. Lethally irradiated wild-type mice transplanted with bone marrow from Abcg5(-/-) mice displayed normal platelets, whereas Abcg5(-/-) mice transplanted with wild-type bone marrow still showed macrothrombocytopenia. Treatment with the sterol absorption inhibitor ezetimibe rapidly reversed macrothrombocytopenia in Abcg5(-/-) mice concomitant with a strong decrease in plasma plant sterols. Thus, accumulation of plant sterols is responsible for development of macrothrombocytopenia in sitosterolemia, and blocking intestinal plant sterol absorption provides an effective means of treatment.