| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Fatty acids in plasma phospholipids and cholesterol esters from identical twins concordant and discordant for schizophrenia Bates, C., D. F. Horrobin, et al. (1991), Schizophr Res 6(1): 1-7. Abstract: The fatty acid compositions of plasma phospholipids and cholesterol esters were measured in 18 pairs of twins discordant for schizophrenia and 20 pairs concordant for schizophrenia. In the twins discordant for schizophrenia the only significant abnormalities were elevations of adrenic (22:4n-6) and docosapentaenoic (22:5n-6) acids in the schizophrenic twins. These fatty acids have also recently been reported to be elevated in brains from schizophrenics. The twins concordant for schizophrenia showed many differences from the normal discordant twins. 22:4n-6 and 22:5n-6 were even more abnormal than in the schizophrenic discordant twins. In addition, linoleic acid was significantly reduced, an abnormality which has been found consistently in other schizophrenic populations. These observations are consistent with the concept that unsaturated fat metabolism may be abnormal in schizophrenia. |
| Fatty acids regulate hepatic low density lipoprotein receptor activity through redistribution of intracellular cholesterol pools Daumerie, C. M., L. A. Woollett, et al. (1992), Proc Natl Acad Sci U S A 89(22): 10797-801. Abstract: When the intake of dietary cholesterol in the hamster is constant, feeding the saturated 14:0 fatty acid (n-tetradecanoic acid) elevates the plasma low density lipoprotein (LDL) cholesterol concentration from 72 to 204 mg/dl, while the monounsaturated 18:1 fatty acid (cis-9-octadecenoic acid) lowers this level to 28 mg/dl. The 14:0 fatty acid lowers the hepatic cholesteryl ester concentration from 12 to 5 mg/g, while the abundance of this fatty acid in the ester fraction is increased 13-fold. Hepatic LDL receptor activity is depressed to 41% of control, while the LDL cholesterol production rate is increased to 132%. These changes account for the 3-fold increase in the plasma LDL cholesterol concentration. In contrast, feeding the 18:1 fatty acid increases hepatic cholesteryl ester concentration to 21 mg/g, and the abundance of this acid in the esters is increased 1.4-fold. Hepatic receptor activity is increased to 145%, while the production rate is suppressed to 68% of control. These changes account for the decrease in plasma LDL cholesterol level to 28 mg/dl. Despite these marked changes in LDL metabolism, however, the 14:0 and 18:1 fatty acids cause no change in net cholesterol balance across the liver. These results suggest that there are two fundamentally different mechanisms regulating hepatic LDL metabolism. One involves changes in net sterol balance across the liver brought about by alterations in the rate of cholesterol or bile acid absorption across the intestine, while the second is articulated through a redistribution of the putative sterol regulatory pool within the hepatocyte that is dictated by the type of long-chain fatty acid that reaches the liver. |
| Fatty acids: links between genes involved in fatty acid and cholesterol metabolism Worgall, T. S. and R. J. Deckelbaum (1999), Curr Opin Clin Nutr Metab Care 2(2): 127-33. Abstract: Fatty acids are a major constituent of dietary fats and form an integral part of the cellular membrane and lipoproteins. The gene regulatory potential of fatty acids has long been recognized, but the precise regulatory mechanisms are unknown. The regulatory ability of fatty acids on the expression of a number of genes together with potential mechanisms and pathways of regulation are reviewed. In this review, we emphasize a key aspect of regulation mediated by the sterol regulatory element binding-protein, and its effects on sterol regulatory elements. |
| Feasibility of monogenic control of blood cholesterol content for the Kirghiz population Ismanilova Ch, S., E. Ginzburg, et al. (1993), Genetika 29(12): 2081-92. Abstract: The samples presented by 67 pedigrees ascertained from the Kirghiz population via proband having an early myocardial infarction were analysed for ischemic heart disease. It is shown that these pathologies are not accompanied by high increase in the cholesterol level, as is usual for the European populations. Segregation analysis of the cholesterol level was performed and a possibility of monogenic control of this trait was demonstrated. |
| Features of cholesterol structure that regulate the clearance of chylomicron-like lipid emulsions Mortimer, B. C., P. Tso, et al. (1995), J Lipid Res 36(9): 2038-53. Abstract: Cholesterol is an absolute requirement for the clearance from plasma of the remnants of triglyceride-rich lipoproteins. Our laboratory previously established that cholesterol was essential for the hepatic uptake of remnant particles after intravenous injection of chylomicron-like lipid emulsions (1). The aim of the present study was to determine the structural features of the cholesterol molecule that regulate the metabolism of chylomicrons. Chylomicron-like lipid emulsions, which reflect the size and composition and mimic the physiology of lymph chylomicrons, were prepared with tracer amounts of labeled triolein (14CTO) and cholesteryl oleate (3HCO) to follow the hydrolysis of triglyceride and the uptake of chylomicron remnant particles by the liver. Sterols selected as cholesterol congeners with functional group variations were incorporated into the emulsions in place of cholesterol and injected intravenously in rats. Control emulsions contained either no cholesterol or approximately 1% (by weight) cholesterol. The effects of the different sterol structures on lipolysis and hepatic remnant uptake were compared with controls to determine the significance of various functional groups. Clearance of emulsion CO was impaired when cholesterol was absent or replaced by cholesteryl chloride, cholesteryl formate, or 3-keto-cholesterol. Clearance of emulsions containing epicholesterol, where the OH group at the 3-position is in the alpha configuration, was similar to control emulsions containing cholesterol. Congeners with an additional hydroxyl group, viz. 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol, or 25-hydroxycholesterol, reduced CO clearance. Androstenol, which lacks the side chain at the C17-position, also retarded CO clearance from plasma. In contrast, emulsions incorporating congeners with side chain variations such as campesterol, beta-sitosterol, stigmasterol, or saturated congeners of cholesterol such as cholestanol, coprostanol and its epimer, epicoprostanol, all were cleared similarly to emulsions containing cholesterol. In conclusion, for physiological clearance of a chylomicron-like emulsion, the presence of a hydroxyl (-OH) group at the 3-position and an alkyl side chain at the C17-position of cholesterol are essential, while the structure of the side chain and the saturation of the ring structure are not critical. The mechanism of the specificity of sterols on the metabolism of protein-free emulsions is unclear, but does not relate to changes in microfluidity of the surface lipids, nor to the amount or isoform of associated apolipoproteins. |
| Features of distribution of free and esterified cholesterol in the epidermis, biological membranes and plasma lipoproteins in psoriasis Fortinskaia, E. S., T. I. Torkhovskaia, et al. (1996), Klin Lab Diagn(4): 38-43. Abstract: The parameters of cholesterol (CS) metabolism in the epidermis, blood plasma lipoproteins, and red cell membranes were assessed in patients with psoriasis. The levels of free and total CS in extracts from the surface of epidermis, in plasma lipoproteins, and in plasma triglycerides were measured, and the molar ratio CS/ phospholipids (CS/PL index) in red cell membranes assessed in 194 patients with psoriasis of different severity. The levels of free and total CS in the epidermis were found to increase as the psoriatic process grew in severity. These shifts manifested even in apparently intact skin sites, which indicated the primary nature of total-system disorders. As for the plasma lipids, statistically reliable changes were observed only for the relative level of free cholesterol of the plasma and, most of all, high-density lipoproteins. These values for the mean parameters in the five groups of examinees correlated (r from 0.71 to 0.92) with the levels of total and free CS in the epidermis. Contrary to it, the levels of total CS and triglycerides in the plasma had a tendency to decrease as the severity of the psoriatic process augmented. Such a trend was statistically reliable for the CS/PL index, which increased in all the patients except the most grave, this increase being the more, the less grave the disease was; this was manifested in an inverse correlation (r = 0.9, on average) with the epidermal CS. The detected uncommon relationship between CS values in the epidermis, plasma lipoproteins, and biological membranes indicates heretofore unknown features of metabolic disorders in psoriasis. |
| Fecal cholesterol excretion in preterm infants fed breast milk or formula with different cholesterol contents Boehm, G., G. Moro, et al. (1995), Acta Paediatr 84(3): 240-4. Abstract: In 44 very low-birth-weight infants, fecal cholesterol excretion was measured and in 29 other infants serum total cholesterol concentrations in response to different cholesterol intakes were studied. The infants received fortified breast milk (mean cholesterol content 15.3 mg/dl) or were fed either a standard preterm formula (cholesterol content 5.5 mg/dl) or the same formula but with a modified lipid composition (long chain polyunsaturated fatty acid concentration closely related to breast milk fat) and 30 mg of cholesterol/dl. In the group fed the high cholesterol formula, fecal cholesterol excretion was significantly higher (35.5 mmol/kg/day) than in the groups fed breast milk or the standard formula (20.1 and 18.2 mmol/kg/day). Cholesterol balance in the group fed the high cholesterol formula (21.8 mg/kg/day) was significantly higher than in the group fed breast milk (+8.6 mg/kg/day). In the infants fed the low cholesterol formula the balance was negative (-7.7 mg/kg/day). Serum concentrations of total cholesterol were similar in the groups fed breast milk or the high cholesterol formula (3.47 and 3.51 mmol/l), but significantly higher than in the group fed the low cholesterol formula (3.15 mmol/l). The data suggest that preterm infants are able to regulate a higher cholesterol intake than during breast feeding by increasing fecal cholesterol excretion as well as decreasing endogenous synthesis. |
| Fecal primary bile acids and serum cholesterol are associated with colorectal adenomas Meance, S., M. C. Boutron-Ruault, et al. (2003), Dig Dis Sci 48(9): 1751-7. Abstract: In order to identify biomarkers of colorectal tumors, 20 subjects with colorectal adenomas were compared with 20 controls as regards fecal parameters (pH, short-chain fatty acids, bile acids, and sterols), blood parameters (bile acids, cholesterol, triglycerides, glycemia and insulinemia), and rectal cell proliferation. Variables were compared by unconditional logistic regression, controlling for gender. There were significant and positive associations between risk of adenoma and total fecal primary bile acids and serum cholesterol, with odds ratios for the third versus first tertile = 9.4 (P for trend = 0.03) and 8.6 (P for trend = 0.04), respectively. There was a trend towards an increased triglycerides level in adenoma subjects compared with controls (P = 0.08). These three parameters correlated with cell proliferation, although cell proliferation itself was not significantly associated with adenomas. In conclusion, these results suggest that fecal primary bile acids and serum cholesterol are markers of early events of colorectal carcinogenesis. |
| Feedback and hormonal regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase: the concept of cholesterol buffering capacity Ness, G. C. and C. M. Chambers (2000), Proc Soc Exp Biol Med 224(1): 8-19. Abstract: Regulation of the expression of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase by the major end product of the biosynthetic pathway, cholesterol, and by various hormones is critical to maintaining constant serum and tissue cholesterol levels in the face of an ever-changing external environment. The ability to downregulate this enzyme provides a means to buffer the body against the serum cholesterol-raising action of dietary cholesterol. The higher the basal expression of hepatic HMG-CoA reductase, the greater the "cholesterol buffering capacity" and the greater the resistance to dietary cholesterol. This review focuses on the mechanisms of feedback and hormonal regulation of HMG-CoA reductase in intact animals rather than in cultured cells and presents the evidence that leads to the proposal that regulation of hepatic HMG-CoA reductase acts as a cholesterol buffer. Recent studies with animals have shown that feedback regulation of hepatic HMG-CoA reductase occurs at the level of translation in addition to transcription. The translational efficiency of HMG-CoA reductase mRNA is diminished through the action of dietary cholesterol. Oxylanosterols appear to be involved in this translational regulation. Feedback regulation by dietary cholesterol does not appear to involve changes in the state of phosphorylation of hepatic HMG-CoA reductase or in the rate of degradation of this enzyme. Several hormones act to alter the expression of hepatic HMG-CoA reductase in animals. These include insulin, glucagon, glucocorticoids, thyroid hormone and estrogen. Insulin stimulates HMG-CoA reductase activity likely by increasing the rate of transcription, whereas glucagon acts by opposing this effect. Hepatic HMG-CoA reductase activity undergoes a significant diurnal variation due to changes in the level of immunoreactive protein primarily mediated by changes in insulin and glucagon levels. Thyroid hormone increases hepatic HMG-CoA reductase levels by acting to increase both transcription and stability of the mRNA. Glucocorticoids act to decrease hepatic HMG-CoA reductase expression by destabilizing reductase mRNA. Estrogen acts to increase hepatic HMG-CoA reductase activity primarily by stabilizing the mRNA. Deficiencies in those hormones that act to increase hepatic HMG-CoA reductase gene expression lead to elevations in serum cholesterol levels. High basal expression of hepatic HMG-CoA reductase, whether due to genetic or hormonal factors, appears to result in greater cholesterol buffering capacity and thus increased resistance to dietary cholesterol. |
| Feedback inhibition of the cholesterol biosynthetic pathway in patients with Smith-Lemli-Opitz syndrome as demonstrated by urinary mevalonate excretion Pappu, A. S., R. D. Steiner, et al. (2002), J Lipid Res 43(10): 1661-9. Abstract: Smith-Lemli-Opitz syndrome (SLOS) is a genetic disorder characterized by low plasma cholesterol and high 7-dehydrocholesterol (7-DHC). Synthesis of cholesterol and 7-DHC and its metabolites is regulated by HMG-CoA reductase, whose activity can be measured by 24-h excretion of its product mevalonate. We devised a simple, non-invasive method for collecting 24-h urine in our subjects. With a background of a very low cholesterol diet, mean mevalonate excretion did not differ between controls and SLOS children, indicating that SLOS subjects have normal HMG-CoA reductase activity. In a short term feeding study, the effects of a high cholesterol diet in SLOS subjects include a significant 55% increase in plasma cholesterol levels and 39% decrease in mevalonate excretion and no change in plasma 7-DHC levels. However, in four SLOS subjects, fed a high cholesterol diet for 2-3 years, plasma cholesterol levels continued to increase, urinary mevalonate excretion remained low and total 7-DHC decreased significantly, likely from decreased total sterol synthesis. Thus, in SLOS subjects, HMG-CoA reductase activity was normal and was subject to normal cholesterol induced feedback inhibition. However, total sterol synthesis in SLOS may still be decreased because of increased diversion of mevalonate into the shunt pathway away from sterol synthesis. |
| Feedback regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity by dietary cholesterol is not due to altered mRNA levels Ness, G. C., R. K. Keller, et al. (1991), J Biol Chem 266(23): 14854-7. Abstract: Feeding rats diets containing 2% cholesterol markedly reduced hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity but had little effect on mRNA levels. Addition of mevalonolactone to the diet further decreased reductase activity independent of a change in mRNA levels. In contrast, farnesyl pyrophosphate synthetase mRNA levels and enzyme activity were decreased to similar degrees in response to dietary cholesterol. Addition of mevalonolactone to the diet did not further decrease farnesyl pyrophosphate synthetase activity. Dietary cholesterol and mevalonolactone had no effect on mRNA levels for "cellular nucleic acid-binding protein" which has been demonstrated to bind the sterol regulatory elements in the HMG-CoA reductase and farnesyl pyrophosphate synthetase promoters. Dietary cholesterol increased cholesterol 7 alpha-hydroxylase mRNA levels as expected. These results suggest that cholesterol-mediated feed-back regulation of hepatic HMG-CoA reductase gene expression does not occur at the level of transcription. |
| Feeding apolipoprotein E-knockout mice with cholesterol and fat enriched diets may be a model of non-alcoholic steatohepatitis Tous, M., N. Ferre, et al. (2005), Mol Cell Biochem 268(1-2): 53-8. Abstract: The present study was aimed (1) to investigate the effect of cholesterol and fat enriched diets on the development of steatohepatitis in apolipoprotein E-knockout mice, and (2) to study the chronological relationships between the development of hepatic alterations, hypercholesterolemia and atherosclerotic lesions in this experimental model. The study consisted of two protocols. Protocol 1 was used in 90 mice subdivided in groups of 18. For 10 weeks, each group was given a diet with different fat and cholesterol contents. Protocol 2 was used in 42 mice, subdivided in four groups. Each group was given a diet enriched with cholesterol and palm oil and they were sacrificed at 8, 13, 18 and 24 weeks of age. Results were as following. (1) Mice given high fat/high cholesterol diets developed an impairment of liver histology consisting of fat accumulation, macrophage proliferation, and inflammation. (2) These effects were modulated by the type of fat: olive oil was mainly associated with macrovesicular steatosis and cholesterol plus palm oil with severe steatohepatitis. (3) There was a chronological and quantitative relationship between liver impairment and the formation of atheromatous lesions. We conclude that apolipoprotein E-knockout mice may be a useful model for investigating the mechanisms of diet-induced steatohepatitis. |
| Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse Wang, D. Q., S. Tazuma, et al. (2003), Am J Physiol Gastrointest Liver Physiol 285(3): G494-502. Abstract: We explored the influence of the hydrophilic-hydrophobic balance of a series of natural bile acids on cholesterol absorption in the mouse. Male C57L/J mice were fed standard chow or chow supplemented with 0.5% cholic; chenodeoxycholic; deoxycholic; dehydrocholic; hyocholic; hyodeoxycholic; alpha-, beta-, or omega-muricholic; ursocholic; or ursodeoxycholic acids for 7 days. Biliary bile salts were measured by reverse-phase HPLC, and hydrophobicity indices were estimated by Heuman's method. Cholesterol absorption efficiency was determined by a plasma dual-isotope ratio method. In mice fed chow, natural proportions of tauro-beta-muricholate (42 +/- 6%) and taurocholate (50 +/- 7%) with a hydrophobicity index of -0.35 +/- 0.04 produced cholesterol absorption of 37 +/- 5%. Because bacterial and especially hepatic biotransformations of specific bile acids occurred, hydrophobicity indices of the resultant bile salt pools differed from fed bile acids. We observed a significant positive correlation between hydrophobicity indices of the bile salt pool and percent cholesterol absorption. The principal mechanism whereby hydrophilic bile acids inhibit cholesterol absorption appears to be diminution of intraluminal micellar cholesterol solubilization. Gene expression of intestinal sterol efflux transporters Abcg5 and Abcg8 was upregulated by feeding cholic acid but not by hydrophilic beta-muricholic acid nor by hydrophobic deoxycholic acid. We conclude that the hydrophobicity of the bile salt pool predicts the effects of individual fed bile acids on intestinal cholesterol absorption. Natural alpha- and beta-muricholic acids are the most powerful inhibitors of cholesterol absorption in mice and might act as potent cholesterol-lowering agents for prevention of cholesterol deposition diseases in humans. |
| Feeding rats the nitric oxide synthase inhibitor, L-N(omega)nitroarginine, elevates serum triglyceride and cholesterol and lowers hepatic fatty acid oxidation Khedara, A., Y. Kawai, et al. (1996), J Nutr 126(10): 2563-7. Abstract: This study was conducted to examine whether nitric oxide regulates lipid metabolism. In Experiment 1, rats were fed for 5 wk diets with or without 0.2 g/kg L-N-nitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase, that were or were not supplemented with 40 g/kg L-arginine. Rats fed L-NNA had significantly higher concentrations of serum triglyceride and total cholesterol, lower concentrations of serum nitrate, and a lower ratio of HDL-cholesterol to total cholesterol than rats fed the basal diet. These alterations were suppressed by supplementing L-arginine to the L-NNA-containing diet. In Experiment 2, rats were fed diets with or without 0.2 g/kg L-NNA. Dietary L-NNA elevated serum concentrations of free fatty acids without affecting those of ketone bodies. L-NNA lowered the activity of hepatic carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, but did not affect activities of hepatic glucose-6-phosphate dehydrogenase and fatty acid synthase which are lipogenic enzymes. These results suggest that the lower nitric oxide level in rats fed L-NNA leads to hyperlipidemia and that the elevation in serum triglyceride might be due to reduced fatty acid oxidation. |
| Feeding trans fatty acids to rats has no effect on the intestinal uptake of glucose, fatty acids or cholesterol Thomson, A. B., M. Garg, et al. (1994), Digestion 55(6): 405-9. Abstract: Trans fatty acids are produced in the manufacture of margarine, and these hydrogenated fatty acids may have a deleterious effect on the reduction in fasting levels of serum cholesterol anticipated from the feeding of cis polyunsaturated fatty acids. We undertook this study in rats to test the effect of feeding trans fatty acids on the intestinal uptake of glucose, fatty acids and cholesterol. Adult female Wistar rats were fed for 2 weeks semisynthetic, isocaloric diets containing no oleic acid (18:1), cis 18:1 or trans 18:1. There was no difference between the three dietary groups in the animals' food consumption or body weight gain. Rats fed trans 18:1 had an approximately 20% decline in the total weight of the ileum as compared with controls fed no 18:1, and therefore there was also a decline in the percentage of the ileal tissue comprised of mucosa. When comparing rats fed trans 18:1 with those fed cis 18:1 or no 18:1, there was no difference in the uptake of varying concentrations of D-glucose when expressed as nmol.100 mg tissue-1.min-1 or nmol.100 mg mucosal-1.min-1 for jejunum or for ileum. Also, there was no difference in the value of the maximal transport rate (Vmax), Michaelis constant (Km), or the contribution of passive uptake of glucose assessed with L-glucose. There was no diet-associated change in the jejunal or ileal uptake of a medium-chain length fatty acid (lauric acid), a long-chain length saturated fatty acid (palmitic acid), a monounsaturated fatty acid (oleic acid), two polyunsaturated fatty acids (linoleic and linolenic acids), or cholesterol. Thus, we conclude that 2 weeks' feeding of trans fatty acid to rats has no influence on the jejunal or ileal uptake of glucose, fatty acids or cholesterol. |
| Feeding unsaponifiable compounds from rice bran oil does not alter hepatic mRNA abundance for cholesterol metabolism-related proteins in hypercholesterolemic rats Nagao, K., M. Sato, et al. (2001), Biosci Biotechnol Biochem 65(2): 371-7. Abstract: The hypocholesterolemic effect of rice bran oil (RBO) is defined in human and animal experiments which indicate the presence of active component(s) in the unsaponifiable fraction, but the detailed mechanism is not known yet. Exogenously hypercholesterolemic (ExHC) rats were fed for 2 weeks on a 0.5% cholesterol diet supplemented with 10% each of RBO, RBO-simulated oil (RBOSO) in its fatty acid composition, or RBOSO plus 0.25% unsaponifiable compounds (UC) from RBO. Rats fed RBO or the UC resulted in lowing serum and liver cholesterol concentration and preventing reduction of high density lipoproteinic-cholesterol. Dietary RBO or the UC led to an elevation of fecal neutral sterol excretion, but no significant change in fecal bile acid excretion or in hepatic abundance of mRNAs for 3-hydroxy-3-methylglutaryl-CoA reductase, cholesterol-7alpha-hydroxylase, and low density lipoprotein receptor. Besides, serum and liver alpha-tocopherol concentrations were lowered in RBO or the UC-fed rats. These results show that the UC in RBO leads to a decreased serum cholesterol concentration by interrupting the absorption of intestinal hydrophobic compounds rather than by modifying cholesterol metabolism in the liver. |
| Femtomole analysis of 9-oxononanoyl cholesterol by high performance liquid chromatography Karten, B., H. Boechzelt, et al. (1998), J Lipid Res 39(7): 1508-19. Abstract: 9-Oxononanoyl cholesterol, a cholesterol core-aldehyde formed during lipoprotein oxidation, was recently identified in advanced human atherosclerotic lesions. Here we present a rapid and sensitive HPLC method for 9-oxononanoyl cholesterol analysis. 9-Oxononanoyl cholesterol was converted to the corresponding fluorescent decahydroacridine derivative by reaction with 1,3-cyclohexanedione. The derivatives formed were purified by solid-phase extraction on C-18 columns, separated by reversed phase HPLC with isocratic elution, and detected by their fluorescence. Decahydroacridine derivatives of 9-oxononanoyl cholesterol were stable for at least 160 h. The limit of quantitation of the method presented is at the low (approximately 50) femtomole level, with an absolute limit of detection (signal: noise = 6) of 15 fmol. Intra-assay variation was < or = 5%, while inter-assay variations were between 5 and 15%, depending on the concentration of the analyte. Standard curves were linear over nearly three orders of magnitude (50 fmol-12.5 pmol). 9-Oxononanoyl cholesterol proved to be the major cholesterol core-aldehyde formed during t-BuOOH/FeSO4 oxidation of cholesteryl linoleate and Cu2+-induced LDL oxidation, findings confirmed by atmospheric pressure chemical ionization-mass spectrometry. Analysis of lipid extracts obtained from advanced human atherosclerotic lesions revealed the presence of 9-oxononanoyl cholesterol in all tissue samples analyzed (28+/-14 micromol/mol cholesterol, n = 9) despite the presence of alpha-tocopherol (4+/-1.2 mmol/mol cholesterol, n = 9). |
| Fermentable carbohydrates exert a more potent cholesterol-lowering effect than cholestyramine Favier, M. L., C. Moundras, et al. (1995), Biochim Biophys Acta 1258(2): 115-21. Abstract: The purpose of this work was to assess the respective role of bile acid excretion and of the end-products of cecal fermentations in the cholesterol-lowering effect of complex carbohydrates. The effects of two different fermentable carbohydrates (guar gum, beta-cyclodextrin), and sequestrant resin (cholestyramine) have been investigated in male Wistar rats. Guar gum and beta-cyclodextrin are broken down in the large bowel, with fermentation rich in propionic acid (37% against 26% for control), whereas cholestyramine did not enhance cecal fermentation. beta-Cyclodextrin and guar gum were less potent than cholestyramine to enhance bile acids and sterol excretion. Nevertheless, fermentable carbohydrates exerted a more potent cholesterol-lowering effect than cholestyramine. beta-Cyclodextrin also depressed triacylglycerol-rich lipoprotein (TGRLP). Fermentable carbohydrates lowered cholesterol of LDL and HDL1 fractions. The induction of hepatic HMG-CoA reductase was practically proportional to rate of fecal steroid excretion. Moreover, with beta-cyclodextrin, hepatic HMG-CoA reductase induction was concomitant to a decrease in fatty acid synthase (FAS) activity. Thus, the cholesterol-lowering effect of fermentable carbohydrates could be related to a depressed lipogenesis, as well as to an accelerated removal of HDL1, in relation to an elevated hepatic demand of cholesterol. In conclusion, fermentable carbohydrates could favour cholesterol elimination and have a general lipid-lowering effect by exerting more complex physiological effects than cholestyramine. |
| Fermentable polysaccharides that enhance fecal bile acid excretion lower plasma cholesterol and apolipoprotein E-rich HDL in rats Moundras, C., S. R. Behr, et al. (1994), J Nutr 124(11): 2179-88. Abstract: The effect of different polysaccharides fermented in the large intestine and liable to lower plasma cholesterol was investigated in rats. Male rats were assigned to one of five treatment groups: control diet or a diet containing pectin, guar gum, gum arabic or beta-cyclodextrin. The four compounds were effectively fermented, yielding cecal short-chain fatty acids (SCFA) concentrations in the range of 130 to 170 mmol/L. Relative to controls, the cecal concentration of propionate was significantly higher in rats fed all fibers, especially those fed guar gum (+190%) or beta-cyclodextrin (+385%). All the fermented carbohydrates elicited a significant cholesterol-lowering effect, which was most potent in rats fed guar gum or beta-cyclodextrin, the two fibers that also significantly depressed plasma triglycerides. These two carbohydrates significantly lowered LDL and HDL1 cholesterol, triglyceride-rich lipoprotein triglycerides and apolipoprotein E levels. Apolipoprotein B was lowered only by beta-cyclodextrin. The microsomal activities of hydroxymethylglutaryl (HMG) CoA reductase and of cholesterol 7 alpha-hydroxylase were markedly elevated in rats fed guar gum or beta-cyclodextrin and, to a lesser extent, in those fed pectin compared with controls. Increased bile acid excretion seems to be essential in the cholesterol-lowering effect of soluble fibers and related compounds. This effect is connected to induction of HMG CoA reductase and lowering concentrations of apolipoprotein E-containing particles. |
| Fermentation of resistant rice starch produces propionate reducing serum and hepatic cholesterol in rats Cheng, H. H. and M. H. Lai (2000), J Nutr 130(8): 1991-5. Abstract: This study was designed to investigate the effects of different proportions of rice starch and cornstarch on lipid metabolism in rats fed high dietary cholesterol. Male Wistar rats were fed a 10 g/100 g fat diet containing 1 g/100 g cholesterol with 0 (control diet), 15, 30, 45 or 63 g/100 g rice starch with an enzyme resistant starch concentration of 1.26, 1.39, 1.52, 1.65 or 1.80 g/100 g, respectively, for 4 wk. Groups fed diets with < 63 g/100 g rice starch were supplemented with cornstarch to 63 g/100 g. The two kinds of starch had different structures as seen using scanning electron microscopy (SEM). The rice starch was an aggregation (n = 20-60) of smaller granules (3-8 microm in diameter), whereas the cornstarch was composed of larger (5-15 microm in diameter), single granules. The compound rice starch (0.99 kg/L) was larger in size and denser in structure than cornstarch (0.63 kg/L). Serum total cholesterol concentrations in rats fed both the 45 and 63 g/100 g rice starch diets were significantly lower than in all other groups (P < 0.05). The serum propionate concentration in the rats fed 63 g/100 g rice starch diets was significantly higher than that of other groups. Hepatic triglyceride and total cholesterol concentrations in rats fed 63 g/100 g rice starch diets were significantly lower than in the control group. These results suggest that, because the compound rice starch was an aggregation of smaller granules, larger in size and denser in structure than cornstarch, it was digested more slowly and altered lipid metabolism. Resistant rice starch may be fermented to produce propionate, which reduces serum and hepatic cholesterol. |