Showing papers on "Sterol published in 1998"
TL;DR: It is concluded that SREBP-2 is a relatively selective activator of cholesterol synthesis, as opposed to fatty acid synthesis, in liver and adipose tissue of mice.
Abstract: We produced transgenic mice that express a dominant-posi- tive truncated form of sterol regulatory element-binding protein-2 (SREBP-2) in liver and adipose tissue. The en- coded protein lacks the membrane-binding and COOH-ter- minal regulatory domains, and it is therefore not susceptible to negative regulation by cholesterol. Livers from the trans- genic mice showed increases in mRNAs encoding multi- ple enzymes of cholesterol biosynthesis, the LDL recep- tor, and fatty acid biosynthesis. The elevations in mRNA for 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase and HMG CoA reductase were especially marked (13-fold and 75-fold, respectively). As a result, the trans- genic livers showed a 28-fold increase in the rate of choles- terol synthesis and a lesser fourfold increase in fatty acid synthesis, as measured by intraperitoneal injection of ( 3 H)water. These results contrast with previously reported effects of dominant-positive SREBP-1a, which activated fatty acid synthesis more than cholesterol synthesis. In adi- pose tissue of the SREBP-2 transgenics, the mRNAs for cholesterol biosynthetic enzymes were elevated, but the mRNAs for fatty acid biosynthetic enzymes were not. We conclude that SREBP-2 is a relatively selective activator of cholesterol synthesis, as opposed to fatty acid synthesis, in liver and adipose tissue of mice. ( J. Clin. Invest. 1998. 101: 2331-2339.) Key words: cholesterollow density lipoprotein • sterol regulatory element binding proteinsfatty acids • transgenic mice
676 citations
TL;DR: This data indicates that sitosterol and 24-methylcholesterol are able to regulate membrane fluidity and permeability in a similar manner to cholesterol in mammalian cell membranes, and might be specifically required for cell proliferation.
467 citations
TL;DR: It is demonstrated that the cDNA that is identified encodes the human sterol Delta7-reductase and that mutations in DHCR7 are responsible for at least some cases of SLOS.
Abstract: Summary The Smith-Lemli-Opitz syndrome (SLOS; also known as “RSH syndrome” [MIM 270400]) is an autosomal recessive multiple malformation syndrome due to a defect in cholesterol biosynthesis. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol levels. On the basis of this biochemical abnormality, it has been proposed that mutations in the human sterol D 7 -reductase (7-DHC reductase; E.C.1.3.1.21) gene cause SLOS. However, one could also propose a defect in a gene that encodes a protein necessary for either the expression or normal function of sterol D 7 -reductase. We cloned cDNA encoding a human sterol D 7 -reductase (DHCR7) on the basis of its homology with the sterol D 7 -reductase from Arabidopsis thaliana, and we confirmed the enzymatic function of the human gene product by expression in SLOS fibroblasts. SLOS fibroblasts transfected with human sterol D 7 -reductase cDNA showed a significant reduction in 7-DHC levels, compared with those in SLOS fibroblasts transfected with the vector alone. Using radiation-hybrid mapping, we show that the DHCR7 gene is encoded at chromosome 11q12-13. To establish that defects in this gene cause SLOS, we sequenced cDNA clones from SLOS patients. In three unrelated patients we have identified four different mutant alleles. Our results demonstrate both that the cDNA that we have identified encodes the human sterol D 7 -reductase and that
389 citations
TL;DR: Recent advances in purification and cloning of these major enzymes in the pathways have led to better understanding the molecular basis of regulation of bile acid synthesis and physiological role of the alternative pathways.
Abstract: Bile acids are important physiological agents required for disposal of cholesterol and absorption of vitamins and fats. Bile acids are synthesized from cholesterol in the liver. Enterohepatic circulation of bile acids is very efficient and plays an important physiological role in lipid absorption and secretion, and regulation of bile acid biosynthesis and cholesterol homeostasis. Conversion of cholesterol to bile acids requires 15 different enzymatic steps. Four cytochrome P450 enzymes play important roles in bile acid biosynthesis. The classic bile acid biosynthesis pathway starts with modification of the sterol ring and followed by side chain cleavage reactions to synthesize cholic acid (CA) and chenodeoxycholic acid (CDCA), the primary bile acids in most species. The first and rate-limiting enzyme in this pathway is cholesterol 7alpha -hydroxylase, a microsomal cytochrome P450, CYP7A. Another microsomal cytochrome P450 sterol 12alpha-hydroxylase (CYP12) is required for the synthesis of cholic acid. Mitochondrial cytochrome P450 sterol 27-hydroxylase (CYP27) catalyzes sterol side chain oxidation to convert C27 sterol to C24 bile acids. An alternative bile acid biosynthesis pathway (acidic) has been known for sometime but only recently has attracted much attention. In this pathway, side chain oxidation precedes modification of the sterol ring. Mitochondrial sterol 27-hydroxylase (CYP27) catalyzes the first reaction and followed by 7alpha-hydroxylation catalyzed by a microsomal oxysterol 7alpha-hydroxylase (CYP7B). Recent advances in purification and cloning of these major enzymes in the pathways have led to better understanding the molecular basis of regulation of bile acid synthesis and physiological role of the alternative pathways.
354 citations
TL;DR: In this article, the authors examined the expression of caveolin in MDCK cells under conditions that vary cellular cholesterol concentration and found that caveolin mRNA levels dropped to one-sixth of control levels after treatment with simvastatin, an inhibitor of cholesterol synthesis, or beta-trimethyl cyclodextrin (CD), a cholesterol sequestering drug.
306 citations
TL;DR: This study demonstrates the complex interactions between bile acid and cholesterol metabolism and the dramatic effects of eliminating a single gene product; however, even though a major catabolic pathway was deleted, cholesterol balance across the animal was maintained.
246 citations
TL;DR: It is evident that sterol 27-hydroxylase is more important for bile acid synthesis in mice than in humans, and the results do not support the contention that 27-Hydroxylated steroids are critical for maintenance of cholesterol homeostasis or levels of vitamin D metabolites in the circulation.
244 citations
TL;DR: It is suggested that HMG-CoA reductase is not the only rate-limiting step in sterol synthesis and its overexpression cannot significantly influence this pathway beyond the sterol precursor squalene.
Abstract: The enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase is known as the rate-limiting enzyme in early sterol biosynthesis in eukaryotic cells. To eliminate this regulation in the yeast Saccharomyces cerevisiae, a truncated HMG1 gene, producing a form of the enzyme that lacks the membrane-binding region (i.e. amino acids 1–552), was constructed and overexpressed in this yeast. The transformed strains accumulated large amounts of the sterol precursor squalene, while the levels of ergosterol and a number of other sterol compounds were only slightly elevated. These findings suggest that HMG-CoA reductase is not the only rate-limiting step in sterol synthesis and its overexpression cannot significantly influence this pathway beyond the sterol precursor squalene.
229 citations
TL;DR: The current data support the emerging view that the nSREBPs act in complementary ways to modulate the lipid composition of cell membranes.
224 citations
TL;DR: The steroidogenic acute regulatory protein (StAR) plays a critical role in steroidogenesis by enhancing the delivery of substrate cholesterol from the outer mitochondrial membrane to the cholesterol side chain cleavage enzyme system on the inner membrane as discussed by the authors.
216 citations
TL;DR: It has now been demonstrated that the steady-state level of LDL-C is predominantly dictated by metabolic events in the liver, and this effect is mediated by the enzyme acyl-CoA:cholesterol acyltransferase (ACAT).
Abstract: Epidemiologic studies over the past 25 years have shown that the level of dietary fat intake is positively correlated with the average serum cholesterol value and mortality from coronary heart disease (CHD). A number of different investigators demonstrated that in addition to total fat, the fatty acid composition of diets influenced serum total cholesterol (TC) in humans. In general, saturated fatty acids were found to elevate the serum cholesterol concentration, and unsaturated fatty acids were found to decrease this value. The lipoprotein fraction most affected was the level of cholesterol carried in low density lipoprotein (LDL-C). It has now been demonstrated that the steady-state level of LDL-C is predominantly dictated by metabolic events in the liver. As the amount of dietary cholesterol entering the body is increased, there is expansion of the sterol pool in the liver cell and down regulation of LDL receptors (LDLR) that are primarily responsible for clearing LDL-C from the blood stream. When dietary cholesterol intake is kept constant, however, long-chain saturated fatty acids further suppress hepatic LDLR activity, whereas several unsaturated fatty acids have the opposite effect. These regulatory events depend upon the availability of the various fatty acids to shift intracellular cholesterol between a regulatory and storage pool of cholesterol, and this effect is mediated by the enzyme acyl-CoA:cholesterol acyltransferase (ACAT).
TL;DR: Results indicate that BSP proteins and HDL play an important role in the sperm sterol efflux that occurs during capacitation, and that the heparin-induced sperm capacitation did not involve the efflux of sperm membrane cholesterol.
Abstract: One of the hypotheses to explain the mechanism of capacitation involves the loss of sperm membrane cholesterol. Here, we studied whether or not the major proteins of bovine seminal plasma designated as BSP-A1, -A2, -A3, and -30-kDa (collectively called BSP proteins), which are implicated in sperm capacitation, induce cholesterol efflux. When epididymal sperm were labeled with [3H]cholesterol and incubated with bovine seminal plasma (0.05-2%) or BSP proteins (20-120 microg/ml) for 8 h, the sperm lost [3H]cholesterol (3.6-fold and 3-fold, respectively). The same results in the presence of BSP-A1/-A2 were obtained (3.5-fold) by direct determination of cholesterol on unlabeled epididymal sperm. Analysis of efflux particles by ultracentrifugation on a sucrose gradient revealed a single symmetrical peak of radioactivity at 1.14 g/ml. Immunoblotting of the fractions obtained from size-exclusion chromatography of the efflux particles showed that a portion of the BSP proteins were associated with [3H]cholesterol. Heparin (12 microg/ml) alone did not stimulate cholesterol efflux. In contrast, high-density lipoprotein (HDL, 100 microg/ml) alone stimulated cholesterol efflux up to 3.1-fold after 8 h. When labeled epididymal sperm were preincubated for 20 min with BSP-A1/-A2 (120 microg/ml), washed, and incubated with HDL (100 microg/ml) for 8 h, the total cholesterol efflux of the sperm suspension was 51.8 +/- 5.0% compared to 39.3 +/- 1.2% when HDL alone was used. These results indicate that BSP proteins and HDL play an important role in the sperm sterol efflux that occurs during capacitation. Furthermore, the heparin-induced sperm capacitation did not involve the efflux of sperm membrane cholesterol.
TL;DR: In this article, the Δ7-sterol reductase (EC 1.3.1) was found to be defective in the Smith-Lemli-Opitz syndrome, a frequent inborn disorder of sterol metabolism.
Abstract: Inhibitors of the last steps of cholesterol biosynthesis such as AY9944 and BM15766 severely impair brain development. Their molecular target is the Δ7-sterol reductase (EC 1.3.1.21), suspected to be defective in the Smith–Lemli–Opitz syndrome, a frequent inborn disorder of sterol metabolism. Molecular cloning of the cDNA revealed that the human enzyme is a membrane-bound protein with a predicted molecular mass of 55 kDa and six to nine putative transmembrane segments. The protein is structurally related to plant and yeast sterol reductases. In adults the ubiquitously transcribed mRNA is most abundant in adrenal gland, liver, testis, and brain. The Δ7-sterol reductase is the ultimate enzyme of cholesterol biosynthesis in vertebrates and is absent from yeast. Microsomes from Saccharomyces cerevisiae strains heterologously expressing the human cDNA remove the C7–8 double bond in 7-dehydrocholesterol. The conversion to cholesterol depends on NADPH and is potently inhibited by AY9944 (IC50 0.013 μM), BM15766 (IC50 1.2 μM), and triparanol (IC50 14 μM). Our work paves the way to clarify whether a defect in the Δ7-sterol reductase gene underlies the Smith–Lemli–Opitz syndrome.
TL;DR: The results suggest that the decrease in cell number and increase in apoptosis associated with SIT treatment are mediated by activating the sphingomyelin cycle.
Abstract: Epidemiological evidence has shown that men consuming a low-fat, high-fiber diet containing high amounts of plant products have a lower risk of prostate cancer than men consuming a Western diet. One of the main differences between these two diets is the type of dietary fat, including dietary sterols. This study was undertaken to compare the effect of two dietary sterols on prostate cancer cells in vitro. beta-Sitosterol (SIT), the most common plant sterol, and cholesterol, an animal sterol, were compared for effect on LNCaP cell growth, differentiation, apoptosis, and sphingomyelin cycle intermediates. Cells were treated for up to seven days with sterols delivered by a cyclodextrin vehicle. Compared with cholesterol, SIT (16 microM) decreased growth by 24% and induced apoptosis fourfold, which was accompanied by cell rounding and a 50% increase in ceramide production. No effect was observed on differentiation as measured by prostate-specific antigen and prostatic acid phosphatase, although total acid phosphatase increased with SIT treatment for up to seven days. The results suggest that the decrease in cell number and increase in apoptosis associated with SIT treatment are mediated by activating the sphingomyelin cycle.
TL;DR: The findings indicate that ceramide-mediated maturation of SREBP-1 maturation is a novel sterol-independent mechanism by which cholesterol homeostasis may be regulated.
TL;DR: The steroid esters of Δ5-3β-Hydroxysteroids in Lipoidal Derivatives Synthesized by Lecithin represent substrates for the cholesterol side-chain cleavage enzyme and have unique actions in blood.
Abstract: I. Introduction A. Obfuscating chemistry and the presumptive steroid acetates B. Sterol esters: substrates for the cholesterol side-chain cleavage enzyme II. Lipoidal Derivatives of Δ5-3β-Hydroxysteroids in the Adrenal and Ovary A. Endogenous steroid esters B. Biosynthetic esterification ofΔ 5-3β-hydroxy-steroids III. Lipoidal Derivatives of Steroids in Peripheral Tissues A. Esterification of steroid hormones B. Esterification of Δ5-3β-hydroxysteroids C. Endogenous esters of sex steroids D. Androsterone esters in breast cyst fluid IV. Lipoidal Derivatives Synthesized by Lecithin:Cholesterol Acyltransferase A. Blood B. Ovarian follicular fluid V. Steroid Esterases VI. Lipoidal Derivatives of Steroid Hormones in Insects VII. Biological Effects of Steroid Esterification A. Potent sex steroids B. Unique actions of the steroid esters in blood VIII. Conclusion
TL;DR: The regulatory defect explains the semidominance and pleiotropic effects of upc2-1, a fungal regulatory family containing the Zn(II)2Cys6 binuclear cluster DNA binding domain which gives a predicted amino acid change from glycine to aspartic acid.
Abstract: Aerobically growing wild-type strains of Saccharomyces cerevisiae are unable to take exogenously supplied sterols from media. This aerobic sterol exclusion is vitiated under anaerobic conditions, in heme-deficient strains, and under some conditions of impaired sterol synthesis. Mutants which can take up sterols aerobically in heme-competent cells have been selected. One of these mutations, designated upc2-1, gives a pleiotropic phenotype in characteristics as diverse as aerobic accumulation of sterols, total lipid storage, sensitivity to metabolic inhibitors, response to altered sterol structures, and cation requirements. During experiments designed to ascertain the effects of various cations on yeast with sterol alterations, it was observed that upc2-1 was hypersensitive to Ca2+. Using resistance to Ca2+ as a screening vehicle, we cloned UPC2 and showed that it is YDR213W, an open reading frame on chromosome IV. This belongs to a fungal regulatory family containing the Zn(II)2Cys6 binuclear cluster DNA binding domain. The single guanine-to-adenine transition in upc2-1 gives a predicted amino acid change from glycine to aspartic acid. The regulatory defect explains the semidominance and pleiotropic effects of upc2-1.
TL;DR: The results strongly suggest that hLBR is a sterol C14 reductase, which is found to be highly susceptible to fenpropimorph and tridemorph, but only moderately susceptible to SR 31747.
TL;DR: Results indicate that the role of ergosterol in stress tolerance is independent of hsps or trehalose.
Abstract: The role of ergosterol in yeast stress tolerance, together with heat shock proteins (hsps) and trehalose, was examined in a sterol auxotrophic mutant of Saccharomyces cerevisiae. Ergosterol levels paralleled viability data, with cells containing higher levels of the sterol exhibiting greater tolerances to heat and ethanol. Although the mutant synthesised hsps and accumulated trehalose upon heat shock to the same levels as the wild-type cells, these parameters did not relate to stress tolerance. These results indicate that the role of ergosterol in stress tolerance is independent of hsps or trehalose.
TL;DR: Zooplankton herbivory does not invalidate the use of these alkenones as a proxy for sea surface temperature and pCO2, and the ratio of long-chainAlkenones and their stable carbon isotopic compositions in I. galbana were identical to those egested in faecal material.
Abstract: The stable carbon isotopic compositions of cholesterol, generally the most dominant sterol in the copepod Temora, bears the δ13C “signature” of its dietary precursor sterol when fed on Isochrysis galbana and Rhodomonas sp. The δ13C of cholesterol in the faecal pellets released from Temora longicornis fed on Rhodomonas sp. is identical to the δ13C of the sterols in the diet, indicating that no significant carbon isotopic fractionation effects occur when the copepod modifies eukaryotic precursor sterols to cholesterol. Furthermore, the ratio of long-chain alkenones and their stable carbon isotopic compositions in I. galbana were identical to those egested in faecal material. Thus Zooplankton herbivory does not invalidate the use of these alkenones as a proxy for sea surface temperature and pCO2.
TL;DR: The studies indicate that the magnitude of net sterol flux through the body is not related to the concentration of high density lipoprotein or apolipoprotein A-I in the plasma, but is probably determined by intracellular processes in the peripheral organs that dictate the rate of movement of cholesterol from the endoplasmic reticulum to the plasma membrane.
TL;DR: The C-4 salt marsh grass, Spartina patens, thrives in the upper portion of the marsh where soil salinities may be equal to coastal seawater, and the plasma membrane molar percentage of sitosterol in total free sterol increased when plants were grown in salt media, while the shoots had a decreases K + content and the roots had a decreased Ca 2+ content.
Abstract: The C-4 salt marsh grass, Spartina patens, thrives in the upper portion of the marsh where soil salinities may be equal to coastal seawater. Spartina patens was grown in hydroponic culture in a greenhouse at 0, 340, and 510 mM NaCl, and measured for growth, tissue cation content, and root plasma membrane (PM) lipid composition. From 0 to 340 and 510 mM, the shoot growth decreased, but root growth was not affected. The Na + content increased in both shoots and roots when plants were grown in salt, while the shoots had a decreased K + content and the roots had a decreased Ca 2+ content. Spartina patens root plasma membrane was isolated with an aqueous polymer two-phase system. The purity of the plasma membrane was verified with cytochemical tests on membrane enzyme markers. Plasma membrane lipids were stable relative to the membrane protein content. Molar percentages of sterols (including free sterols) and phospholipid decreased with increasing salinity. However, glycolipid showed a statistically significant increase in the total lipid as salinity in the medium was increased from 0 to 510 mM. Even at a salinity of 510 mM, the plasma membrane sterol/phospholipid ratio was unaffected by NaCI. When the plants were grown in NaCI media, the plasma membrane had a decreased phosphatidylcholine (PC) and phosphatidylethanolamine (PE) content, but the PC/PE ratios were not affected. The plasma membrane molar percentage of sitosterol in total free sterol increased when plants were grown in salt media. The predominant membrane fatty acids were C11 and C14, and the major unsaturated one was C14:1. An increase in growth medium salinity resulted in a decreased root plasma membrane fluidity.
TL;DR: While male and female CD‐1 mice do not differ qualitatively in the way cholesterol feeding changes their bile acid metabolism, the inherently larger bile acids in the female likely facilitates the delivery of significantly more dietary cholesterol to the liver than is the case in males, thereby resulting in higher steady‐state hepatic cholesterol levels.
TL;DR: In this paper, the importance of the biliary pathway in cholesterol homeostasis was evaluated by determining the effects of mdr2 P-glycoprotein deficiency on hepatic and plasma lipid levels and cholesterol kinetics in chow-fed mice.
TL;DR: It is demonstrated that erg26 mutants grown on various sterol and heme-supplemented media accumulate nonesterified carboxylic acid sterols such as 4beta-methyl-4alpha-carboxy-cholesta-8,24-dien-3beta-o l, the predicted substrates for the C-3 sterol dehydrogenase.
Abstract: All but two genes involved in the ergosterol biosynthetic pathway in Saccharomyces cerevisiae have been cloned, and their corresponding mutants have been described. The remaining genes encode the C-3 sterol dehydrogenase (C-4 decarboxylase) and the 3-keto sterol reductase and in concert with the C-4 sterol methyloxidase (ERG25) catalyze the sequential removal of the two methyl groups at the sterol C-4 position. The protein sequence of the Nocardia sp NAD(P)-dependent cholesterol dehydrogenase responsible for the conversion of cholesterol to its 3-keto derivative shows 30% similarity to a 329-aa Saccharomyces ORF, YGL001c, suggesting a possible role of YGL001c in sterol decarboxylation. The disruption of the YGL001c ORF was made in a diploid strain, and the segregants were plated onto sterol supplemented media under anaerobic growth conditions. Segregants containing the YGL001c disruption were not viable after transfer to fresh, sterol-supplemented media. However, one segregant was able to grow, and genetic analysis indicated that it contained a hem3 mutation. The YGL001c (ERG26) disruption also was viable in a hem 1Δ strain grown in the presence of ergosterol. Introduction of the erg26 mutation into an erg1 (squalene epoxidase) strain also was viable in ergosterol-supplemented media. We demonstrated that erg26 mutants grown on various sterol and heme-supplemented media accumulate nonesterified carboxylic acid sterols such as 4β,14α-dimethyl-4α-carboxy-cholesta-8,24-dien-3β-ol and 4β-methyl-4α-carboxy-cholesta-8,24-dien-3β-ol, the predicted substrates for the C-3 sterol dehydrogenase. Accumulation of these sterol molecules in a heme-competent erg26 strain results in an accumulation of toxic-oxygenated sterol intermediates that prevent growth, even in the presence of exogenously added sterol.
TL;DR: It is hypothesize that a radical decrease of 24-methyl cholesterol and/or a concomitant increase of sitosterol would be responsible for a change in cell division through as-yet unknown mechanisms.
Abstract: Higher plants synthesize 24-methyl sterols and 24-ethyl sterols in defined proportions. As a first step in investigating the physiological function of this balance, an Arabidopsis cDNA encoding an S-adenosyl-L-methionine 24-methylene lophenol-C24(1)-methyltransferase, the typical plant enzyme responsible for the production of 24-ethyl sterols, was expressed in tobacco (Nicotiana tabacum L.) under the control of a constitutive promoter. Transgenic plants displayed a novel 24-alkyl-Delta5-sterol profile: the ratio of 24-methyl cholesterol to sitosterol, which is close to 1 in the wild type, decreased dramatically to values ranging from 0.01 to 0.31. In succeeding generations of transgenic tobacco, a high S-adenosyl-L-methionine 24-methylene lophenol-C24(1)-methyltransferase enzyme activity and, consequently, a low ratio of 24-methyl cholesterol to sitosterol, was associated with reduced growth compared with the wild type. However, this new morphological phenotype appeared only below the threshold ratio of 24-methyl cholesterol to sitosterol of approximately 0.1. Because the size of cells was unchanged in small, transgenic plants, we hypothesize that a radical decrease of 24-methyl cholesterol and/or a concomitant increase of sitosterol would be responsible for a change in cell division through as-yet unknown mechanisms.
TL;DR: Results demonstrate both a potential role for cholesterol sulfate-to-cholesterol processing in normal permeability barrier homeostasis, and that basal levels of steroid sulfatase are sufficient to accommodate acute insults to the permeable barrier.
TL;DR: C18 fatty acids can potentiate the biological activities of a typical, regulatory sterol: 25-hydroxycholesterol and it is shown that C18 fatty acid supplementation can enhance the inhibitory effect of 25-Hydroxych cholesterol on sterol and fatty acid biosynthesis.
TL;DR: It is shown that unitary channels that appear in a cholesterol containing membrane also appear when this membrane is free of cholesterol, and the idea that the role of sterols in the formation of the amphotericin B channel is related to the effects they have on the structure of the membrane itself, rather than to a direct involvement in the channel formation is advanced.
TL;DR: It is suggested that the fruiting body of the straw mushroom lowers elevated plasma cholesterol in hypercholesterolemic hamsters, whereas the mycelium does not.
Abstract: The effect of the fruiting body and mycelium of Volvariella volvacea (straw mushroom) on the concentrations of plasma lipids, liver cholesterol, fecal neutral sterol and bile acid excretions was investigated in male Golden Syrian hamsters. The hamsters were fed a purified hypercholesterolemic diet (0.1% cholesterol, 10% fat) for 4 wk to elevate plasma lipid concentrations. Twelve hamsters with elevated plasma total cholesterol were randomly assigned to each treatment group: control (5% cellulose), mushroom fruiting body (5%) and mushroom mycelium (5%). After 4 wk of mushroom diet consumption, the plasma total cholesterol, HDL cholesterol, and combined VLDL + LDL cholesterol concentrations (mmol/L) were significantly lower than control in the group fed the fruiting body-diet (40, 38 and 43%, respectively) (P 0.05) in the excretion of fecal bile acids were observed among groups fed the mushroom diets and the control diet, the mushroom fruiting body diet-fed hamsters apparently had less bacterial degradation of cholic acid as indicated by a significantly greater proportion (P < 0.05) of fecal cholic acid than in controls. They also had a significantly lower proportion of fecal deoxycholic acid (P < 0.05). This study suggests that the fruiting body of the straw mushroom lowers elevated plasma cholesterol in hypercholesterolemic hamsters, whereas the mycelium does not.