| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol 7 alpha-hydroxylase activity in hypothyroidism and hyperthyroidism in humans Sauter, G., M. Weiss, et al. (1997), Horm Metab Res 29(4): 176-9. Abstract: Alterations of serum cholesterol levels are well recognized findings in hypothyroidism and hyperthyroidism. It remains unclear, whether thyroid hormones may affect serum concentrations of cholesterol through changes in the activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolic conversion of cholesterol to bile acids. We determined serum concentrations of the bile acid precursor 7 alpha-hydroxy-4-cholesten-3-one, which reflects cholesterol 7 alpha-hydroxylase activity in the liver, in 19 patients with hypothyroidism and in 10 patients with hyperthyroidism before and after treatment, respectively. In patients with hypothyroidism, serum concentrations of cholesterol and LDL-cholesterol decreased by 33% (p < 0.0005) and 39% (p < 0.0005), respectively, after replacement therapy with thyroid hormones. In contrast, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one (21.7 +/- 15.8 ng/ml vs 24.5 +/- 18.1 ng/ml before treatment, n.s.) as well as serum HDL-cholesterol were unchanged during substitution therapy. In patients with hyperthyroidism, serum concentrations of cholesterol and LDL-cholesterol increased by 27% (p < 0.01) and 39% (p < 0.01) after antithyroid treatment, respectively. Again, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one did not change significantly during treatment (15.8 +/- 12.6 ng/ml vs 14.7 +/- 8.1 ng/ml before treatment, n.s.). These findings indicate that in humans, thyroid hormones influence serum lipid concentrations by other mechanisms than by affecting the activity of cholesterol 7 alpha-hydroxylase. |
| Cholesterol 7 alpha-hydroxylase activity is increased by dietary modification with psyllium hydrocolloid, pectin, cholesterol and cholestyramine in rats Matheson, H. B., I. S. Colon, et al. (1995), J Nutr 125(3): 454-8. Abstract: Sources of dietary fiber known to alter cholesterol metabolism and/or bile acid pool size were fed to rats, and activity of the rate-limiting step in bile acid synthesis, cholesterol 7 alpha-hydroxylase, was measured. In the first experiment, semipurified diets containing 5% cellulose, psyllium hydrocolloid, pectin or oat bran as dietary fiber sources or 2% cholestyramine were fed to groups of 10 male Wistar rats for 4 wk. In the second experiment, groups of six rats were fed diets containing 5% cellulose, rice bran, oat bran or psyllium with and without 0.25% cholesterol. In the first experiment, the activity of cholesterol 7 alpha-hydroxylase (pmol.min-1.mg protein-1) was highest in the cholestyramine-treated group (95.6 +/- 3.6), followed by groups fed psyllium (35.5 +/- 3.5) or pectin (36.0 +/- 4.5), which exhibited more than twice the enzyme activity of groups fed cellulose (16.9 +/- 1.9) or oat bran (12.3 +/- 2.0). In the second experiment, feeding cholesterol resulted in significantly higher enzyme activity when cellulose (65%), oat bran (118%) and rice bran (60%) were fed, but no difference in activity was observed when cholesterol was added to the psyllium-containing diet. Higher activity of cholesterol 7 alpha-hydroxylase when pectin or psyllium rather than cellulose was fed may explain the almost twofold higher bile acid pool sizes previously reported in response to feeding either of these fibers. These data support the hypothesis that the hypocholesterolemic effect of soluble fibers is modulated through increased synthesis and therefore pool size of bile acids. |
| Cholesterol 7 alpha-hydroxylase is up-regulated by the competitive inhibitor 7-oxocholesterol in rat liver Breuer, O., E. Sudjana-Sugiaman, et al. (1993), Eur J Biochem 215(3): 705-10. Abstract: Rats of the Sprague-Dawley strain were infused intravenously with a fat emulsion (Intralipid, trademark of Kabi Pharmacia, Uppsala, Sweden) containing 7-oxocholesterol. This resulted in an increased cholesterol 7 alpha-hydroxylase activity in liver microsomes as compared to controls and was accompanied by increased levels of cholesterol 7 alpha-hydroxylase mRNA and microsomal cholesterol 7 alpha-hydroxylase protein. Rats were also fed a cholestyramine-supplemented diet and infused with 7-oxocholesterol. These animals excreted about half as much bile acids in faeces as cholestyramine-fed controls. Addition of 7-oxocholesterol to liver microsomes from normal rats in amounts corresponding to those present in microsomes from 7-oxocholesterol-treated rats inhibited the cholesterol 7 alpha-hydroxylase activity by about 75%. Cholesterol induced a type-I binding spectrum when added to a purified bacterial-expressed cholesterol 7 alpha-hydroxylase (P-450c7 delta 2-24). 7-Oxocholesterol competitively inhibited the cholesterol binding spectrum, while 7 beta-hydroxycholesterol did not interfere with binding of cholesterol to the enzyme. It is concluded that treatment with the competitive inhibitor 7-oxocholesterol leads to a reduced bile acid biosynthesis and, as a consequence of reduced bile acid inhibition, a compensatory increase in cholesterol 7 alpha-hydroxylase synthesis. The high enzyme activity measured in microsomal preparations from 7-oxocholesterol-treated rats may be due to a continuous conversion of 7-oxocholesterol into less inhibitory metabolites, e.g. 7 beta-hydroxycholesterol. The latter compound was found in high concentrations in liver microsomes from rats treated with 7-oxocholesterol. The physiological importance of these results is discussed in relation to the previous findings that 7-oxocholesterol is accumulated in liver after cholesterol feeding and that 7-oxocholesterol is formed from cholesterol during lipid peroxidation. |
| Cholesterol 7 alpha-hydroxylase: evidence for transcriptional regulation by cholesterol or metabolic products of cholesterol in the rat Jones, M. P., W. M. Pandak, et al. (1993), J Lipid Res 34(6): 885-92. Abstract: Cholesterol 7 alpha-hydroxylase, the rate-determining enzyme in the bile acid biosynthesis pathway, is regulated in a negative feedback manner by hydrophobic bile salts returning to the liver via the portal circulation. The role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase and the interrelationship between the cholesterol and bile acid biosynthesis pathways remain controversial. The objective of the present study was to define the role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase and determine the molecular level of its control. In order to avoid intestinal or intravenous administration of cholesterol, we manipulated the flow of cholesterol within the hepatocytes by decreasing cholesterol synthesis with lovastatin in bile fistula rats (bile acid synthesis is up-regulated), or by increasing cholesterol supply by administering mevalonate, a precursor of cholesterol, to rats with intact enterohepatic circulation (bile acid synthesis is normal). In the first series of studies, lovastatin was administered as a single intravenous bolus (10 mg/kg) to rats with chronic bile fistula and to rats with intact enterohepatic circulation (cholesterol and bile acid synthesis is normal). Three hours after lovastatin administration, cholesterol 7 alpha-hydroxylase specific activity, enzyme mass, mRNA, and gene transcriptional activity were decreased by 35%, 32%, 56%, and 34%, respectively, in rats with chronic bile fistula. In rats with intact enterohepatic circulation, lovastatin administration resulted in a similar decrease (34%) of cholesterol 7 alpha-hydroxylase specific activity.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Cholesterol 7alpha-hydroxylase deficiency in mice on an APOE*3-Leiden background impairs very-low-density lipoprotein production Post, S. M., M. Groenendijk, et al. (2004), Arterioscler Thromb Vasc Biol 24(4): 768-74. Abstract: OBJECTIVE: Cholesterol 7alpha-hydroxylase (cyp7a1) catalyzes the rate-limiting step in conversion of cholesterol to bile acids. To study the relationship between bile acid biosynthesis and triglyceride metabolism, we cross-bred mice lacking cyp7a1 on a hyperlipidemic APOE*3-Leiden background. METHODS AND RESULTS: Female mice received a chow or lipogenic diet. On both diets, fecal bile acid excretion was 70% decreased concomitantly with a 2-fold increased neutral sterol output. The differences in bile acid biosynthesis did not change plasma cholesterol levels. However, plasma triglyceride levels decreased by 41% and 38% in the cyp7a1-/-. APOE*3-Leiden mice as compared with APOE*3-Leiden mice on chow and lipogenic diet, respectively. Mechanistic studies showed that very-low-density lipoprotein (VLDL)-apolipoprotein B and VLDL-triglyceride production rates were reduced in cyp7a1-/-. APOE*3-Leiden mice as compared with APOE*3-Leiden mice (-34% and -35%, respectively). Cyp7a1 deficiency also increased the hepatic cholesteryl ester and triglyceride content (2.8-fold and 2.5-fold, respectively). In addition, hepatic anti-oxidative vitamin content, which can influence VLDL-production, was lower. Hepatic mRNA analysis showed decreased expression of genes involved in lipogenesis including srebf1. CONCLUSIONS: Cyp7a1 deficiency in APOE*3-Leiden mice decreases the VLDL particle production rate, as a consequence of a strongly reduced bile acid biosynthesis, leading to a decrease in plasma triglycerides. These data underscore the close relationship between bile acid biosynthesis and triglyceride levels. |
| Cholesterol 7alpha-hydroxylase influences the expression of hepatic apoA-I in two inbred mouse strains displaying different susceptibilities to atherosclerosis and in hepatoma cells Dueland, S., D. France, et al. (1997), J Lipid Res 38(7): 1445-53. Abstract: C57BL/6 mice are susceptible to diet-induced atherosclerosis, whereas BALB/c mice are resistant. The susceptibility of C57BL/6 mice has been linked to decreased plasma HDL cholesterol in response to a diet containing fat, cholesterol, and cholic acid. Feeding C57BL/6 mice a diet consisting of fat and cholesterol, but no cholic acid, increased plasma high density lipoprotein (HDL) cholesterol. The increase in HDL was associated with increases in both plasma apolipoprotein (apo)A-I and hepatic apoA-I mRNA. Supplementation of the cholesterol-rich diet with cholic acid inhibited the stimulatory effect of cholesterol on hepatic apoA-I mRNA expression, resulting in similar hepatic apoA-I mRNA levels compared to chow-fed mice. Atherosclerosis-resistant BALB/c mice were also resistant to diet-induced changes in plasma HDL, apoA-I, and hepatic apoA-I mRNA levels. Previous studies showed that the diets changed both the activity and mRNA encoding the liver specific enzyme 7alpha-hydroxylase (1993.J. Lipid Res. 34: 923-931). In both strains of mice, hepatic expression of apoA-I and 7alpha-hydroxylase mRNA varied in parallel. Whereas susceptible C57BL/6 mice also showed a significant correlation between HDL cholesterol and expression of 7alpha-hydroxylase, no such correlation was observed in BALB/c mice, suggesting that genetic differences in HDL metabolism, not hepatic apoA-I synthesis, are responsible for the strain specific differences in plasma HDL levels. The finding that lecithin: cholesterol acyltransferase (LCAT) activity was significantly decreased in C57BL/6 mice, but not in BALB/ c mice fed the atherogenic diet, further supports this conclusion. Additional studies show that McArdle hepatoma cells stably expressing plasmid-derived rat 7alpha-hydroxylase recapitulated the parallel linear relationship between 7alpha-hydroxylase and apoA-I mRNA expression observed in both strains of mice. These data link hepatic apoA-I mRNA expression to hepatic cholesterol/bile acid metabolism. |
| Cholesterol 7alpha-hydroxylase is phosphorylated at multiple amino acids Stroup, D. and J. R. Ramsaran (2005), Biochem Biophys Res Commun 329(3): 957-65. Abstract: The activity of cholesterol 7alpha-hydroxylase (gpCYP7A1), the rate limiting enzyme in bile acid synthesis, has been postulated to be regulated by phosphorylation/dephosphorylation. This study has found that several kinase activators rapidly reduce the amount of bile acid produced by the human hepatoma cell line, HepG2, and that gpCYP7A1 from HepG2 cell extracts eluted in the phosphoprotein fraction of FeIII columns. After incubating the HepG2 cells with radioactive orthophosphate, the band identified as gpCYP7Al on immunoblots was strongly labeled. Recombinant gpCYP7A was expressed as 6xHIS fusion polypeptides and subjected to kinase assays. The locations of phosphorylation were mapped further by screening synthetic peptides against AMP-activated protein kinase (AMPK), c-Jun N-terminal kinase, protein kinase A, and a panel of nine protein kinase C isoforms. AMPK, also known as 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase, phosphorylated cholesterol 7alpha-hydroxylase, suggesting a potential mechanism of coordination of cholesterol synthesis and degradation. |
| Cholesterol 7-hydroperoxides in rat skin as a marker for lipid peroxidation Yamazaki, S., N. Ozawa, et al. (1999), Biochem Pharmacol 58(9): 1415-23. Abstract: Concentrations of cholesterol 7alpha- and 7beta-hydroperoxides (Ch 7-OOHs) in the skin of rats were determined by HPLC with a chemiluminescence detector. We demonstrated that (a) the concentrations of Ch 7-OOHs in rat skin were highly correlated with rat age (r = 0.929; N = 51, 1 to 55 weeks old), (b) the concentrations of Ch 7-OOHs in the skin of rats in an ambient light room were not significantly different from those found in rats kept in a dark room for 12 weeks, and (c) lipid peroxidation in vitro induced by ADP-Fe2+ caused an increase in the concentrations of Ch 7-OOHs in homogenates of rat skin. These results indicated that levels of Ch 7-OOHs in skin might be a good marker for aging of rats and might be independent of housing illumination, thus a good marker for endogenous lipid peroxidation. Furthermore, we observed that ultraviolet light B (UVB) irradiation markedly enhanced the concentrations of Ch 7-OOHs in the skin of rats in vivo depending on the duration of the irradiation, and the increases in Ch 7-OOHs were inhibited by radical scavengers, i.e. tocopherols. Therefore, it was suggested that the levels of Ch 7-OOHs in the skin could also be a good marker for UVB-dependent lipid peroxidation. |
| Cholesterol 7-hydroxylase knockout mouse: a model for monohydroxy bile acid-related neonatal cholestasis Arnon, R., T. Yoshimura, et al. (1998), Gastroenterology 115(5): 1223-8. Abstract: BACKGROUND & AIMS: Cyp 7-/- mice lack a functional cholesterol 7alpha-hydroxylase enzyme and develop cholestasis before up-regulation of 27-hydroxycholesterol 7alpha-hydroxylase activity. Because 7alpha-hydroxylation is not the initial step in this metabolic pathway, we tested the hypothesis that cholesterol 27-hydroxylase is expressed at an earlier step and leads to the production of monohydroxy bile acids. METHODS: Polymerase chain reaction with specific oligonucleotides was used to detect messenger RNA (mRNA) coding for cholesterol 27-hydroxylase in 5-day-old normal and Cyp 7-/- mice. Gas-liquid chromatography-mass spectrometry and reverse isotope dilution were used to identify intermediates in the cholesterol 27-hydroxylase metabolic pathway. Light and electron microscopy were used to evaluate the morphological appearance of the liver. RESULTS: mRNA for cholesterol 27-hydroxylase was identified in the liver and spleen. The monohydroxy bile acids 3beta-hydroxy-5-cholenoate and 3alpha-hydroxy-5beta-cholanoate together with their precursor, 27-hydroxycholesterol, were identified in liver homogenates. Cholestasis, present focally, was manifested as dilated bile canaliculi, partial loss of microvilli, and retention of electron-dense biliary material. CONCLUSIONS: The cholesterol 27-hydroxylase metabolic pathway of bile acid synthesis is expressed in neonatal life. The absence of 7alpha-hydroxylase activities unmasks the cholestatic potential of monohydroxy bile acids. The Cyp 7-/- knockout mouse mimics cholestatic events known to occur in humans and provides a unique opportunity for studying regulatory determinants. |
| Cholesterol absorption and cholesterol and bile acid synthesis in two brothers with IDDM and diarrhea Gylling, H. and T. A. Miettinen (1994), Diabetes Care 17(11): 1345-7. Abstract: OBJECTIVE--To determine the best possible treatment for two brothers who had IDDM and bile acid malabsorption-associated disabling diarrhea that was resistant to cholestyramine, antibiotics, clonidine, loperamide, or anticholinergic drugs. RESEARCH DESIGN AND METHODS--Our study paired these two brothers with control subjects. Serum noncholesterol sterols and fecal elimination of cholesterol and plant sterols were quantitated by gas-liquid chromatography. RESULTS--Fecal losses of bile acids exceeded four to six times the control values, and cholesterol synthesis was increased two to three times. Cholesterol absorption efficiency and serum cholesterol concentrations were, respectively, within the high and low control range. CONCLUSIONS--Bile acid malabsorption might have resulted from deranged intestinal motility, possibly contributed by gastrointestinal neuropathy, and some genetic factor. |
| Cholesterol absorption and excretion in ileostomy subjects on high- and low-dietary-cholesterol intakes Ellegard, L. and I. Bosaeus (1994), Am J Clin Nutr 59(1): 48-52. Abstract: Six healthy ileostomy subjects were given 3Hcholesterol and 14Cbeta-sitosterol in a single meal together with two controlled diets containing 150 or 450 mg cholesterol/d. Each diet was eaten for 3 d. Cholesterol absorption and excretion of cholesterol, bile acids, fat, energy, and nitrogen were analyzed. Fractional cholesterol absorption increased from 44 +/- 2.6% (mean +/- SE) to 61 +/- 3.4% (P < 0.05), but absolute cholesterol absorption decreased from 191 +/- 11 to 94 +/- 9 mg/d (P < 0.05) on low cholesterol intake compared with high cholesterol intake. Weight of ileostomy effluent, or excretion of energy, nitrogen, fat, and bile acids did not differ between periods. Endogenous cholesterol excretion remained unchanged whereas net cholesterol excretion (output minus intake) was 37% higher (P < 0.05) on low compared with high cholesterol intake. |
| Cholesterol absorption and hepatic acyl-coenzyme A:cholesterol acyltransferase activity play major roles in lipemic response to dietary cholesterol and fat in laboratory opossums Kushwaha, R. S., J. F. Vandeberg, et al. (2004), Metabolism 53(6): 817-22. Abstract: Partially inbred lines of laboratory opossums differ considerably in their low-density lipoprotein (LDL) cholesterol responses to dietary cholesterol and fat. Genetic analysis suggested that a single major gene is responsible for the variation in LDL cholesterol on the high cholesterol and high fat (HCHF) diet. We measured cholesterol absorption and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in intestine and liver to narrow the search for the major gene. We measured plasma lipoproteins and percent cholesterol absorption by the fecal isotope ratio method in high and low responding lines of opossums on basal and HCHF diets. We also measured lipids in liver and ACAT activity in liver and intestine on the HCHF diet. High and low lines exhibited no differences in percent cholesterol absorption on the basal diet. However, high responding opossums had significantly higher percent cholesterol absorption, hepatic free and esterified cholesterol, and hepatic ACAT activity than low responding opossums on the HCHF diet. Hepatic ACAT activity but not the intestinal ACAT activity was associated with hepatic cholesterol concentration and percent cholesterol absorption. Cholesterol absorption is a major determinant of diet-induced hyperlipidemia in opossums. Hepatic ACAT activity but not the intestinal ACAT may also play a role in diet-induced hyperlipidemia in opossums. |
| Cholesterol absorption and lipoprotein metabolism in type II diabetes mellitus with and without coronary artery disease Gylling, H. and T. A. Miettinen (1996), Atherosclerosis 126(2): 325-32. Abstract: Hypercholesterolemia is an important atherogenic risk factor in type II diabetes, and although coronary artery disease (CAD) is frequent in these patients, it is not known whether cholesterol and lipoprotein metabolism differ in patients with (CAD+) and without CAD (CAD-). Our aim was to study cholesterol metabolism and lipoprotein kinetics in mildly hypercholesterolemic type II diabetic men with and without CAD under similar dietary conditions. Despite similar serum and lipoprotein cholesterol levels, and kinetics of total and dense LDL apo B, light and dense LDL particles were cholesterol-enriched only in CAD+ subjects. Apolipoprotein A-II level was lower in CAD+ than in CAD- subjects (27.1 +/- 0.7 versus 30.9 +/- 0.7 mg/dl, P < 0.05), HDL cholesterol and apolipoprotein A-I kinetics were similar in the two groups. Cholesterol absorption was significantly higher in the CAD+ versus CAD- subjects (27 +/- 2 versus 20 +/- 3%, P < 0.05). In multiple logistic stepwise regression analysis with CAD as the dependent variable, cholesterol absorption efficiency and serum plant sterol/cholesterol proportions were the only variables significantly associated with CAD. In conclusion, in mildly hypercholesterolemic type II diabetic patients, the only metabolic parameter differentiating CAD patients from non-CAD ones was significantly higher cholesterol absorption efficiency in the coronary patients, which could contribute to the finding of the atherogenic cholesterol-rich dense LDL subfraction in these patients. Thus, a treatment causing cholesterol malabsorption by sitostanol alone or in combination with statin could be beneficial in these patients. |
| Cholesterol absorption and metabolism and LDL kinetics in healthy men with different apoprotein E phenotypes and apoprotein B Xba I and LDL receptor Pvu II genotypes Gylling, H., K. Kontula, et al. (1995), Arterioscler Thromb Vasc Biol 15(2): 208-13. Abstract: Apoprotein (apo) E, apoB Xba I, and LDL receptor gene Pvu II polymorphisms are associated with LDL cholesterol level, but little is known about cholesterol and LDL metabolism in subjects with the latter two genetic polymorphisms alone or in combination with different apoE phenotypes. We studied cholesterol absorption efficiency, cholesterol and bile acid synthesis, and LDL apoB kinetics in 52 healthy men and related the metabolic results to the apoB Xba I and LDL receptor Pvu II restriction fragment length polymorphism (RFLP) and apoE phenotypes. New findings were as follows. ApoB Xba I polymorphism was not associated with the metabolic variables of cholesterol, but LDL receptor Pvu II RFLP was associated with fractional catabolic rate for LDL apoB, cholesterol absorption, and cholesterol and bile acid synthesis. ApoE polymorphism exerted the most powerful effect on the LDL cholesterol concentration, so that the apoE2 subjects had the lowest LDL cholesterol and apoB levels and cholesterol absorption, and the highest fractional catabolic rate and bile acid and cholesterol synthesis compared with the apoE3 or especially apoE4 phenotypes in different genetic combinations. In multiple stepwise regression analysis with LDL cholesterol as the dependent and the genetic and metabolic parameters as the independent variables, 47.0% (n = 35, P <.001) of the variability of LDL cholesterol was explained by the apoE polymorphism, 7.1% (P <.05) by the LDL receptor Pvu II RFLP, and 11.3% (P <.01) by bile acid synthesis, while the contribution of the apoB Xba I RFLP was nonsignificant.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Cholesterol absorption and metabolism in the small intestine Stange, E. F., G. Rogler, et al. (1991), Z Gastroenterol Verh 26: 100-1. |
| Cholesterol absorption and synthesis after autotransplantation of porcine ileum Pakarinen, M. P., T. A. Miettinen, et al. (1996), Surgery 120(5): 822-30. Abstract: BACKGROUND: Cholesterol, long-chain fatty acids, and fat-soluble vitamins are absorbed mainly in the upper small intestine and bile acids in the terminal ileum. This study determined the consequences of ileal autotransplantation on cholesterol metabolism, plasma fatty acids, and vitamin A absorption. METHODS: Plasma lipids, cholesterol precursors, plant sterols, cholestanol, fatty acids, vitamin A absorption, and animal growth were studied for 3 months after transection (n = 5), jejunal (50%) resection (n = 7), jejunal (50%) resection combined with orthotopic ileal autotransplantation (n = 7), and enterectomy (n = 7). RESULTS: Cholesterol precursor to cholesterol proportions in plasma (reflect cholesterol synthesis) remained unchanged after transection and jejunal resection. The plasma plant sterol proportions (reflect cholesterol absorption) and retinol absorption increased after transection and less significantly after jejunal resection, whereas plasma fatty acid compositions were virtually unchanged. Transplantation of ileum and enterectomy amended up to sixfold the precursor proportions (p < 0.05 versus transection or jejunal resection) and impaired body weight gain. The plant sterol proportions, vitamin A absorption, and plasma cholesterol levels, respectively, were significantly (p < 0.05) decreased after transplantation when compared with those of the transected control group but remained markedly higher than those in the enterectomized group. Linoleic acid was significantly (p < 0.05 versus transection) decreased, whereas monoenoic fatty acids and eicosatrienoic acid were increased (p < 0.05 versus jejunal resection) in plasma lipids. CONCLUSIONS: These results indicate that autotransplantation of ileum in pigs that have undergone jejunectomy impairs sterol, essential fatty acid, and vitamin A absorption so that plasma cholesterol levels decrease despite markedly increased cholesterol synthesis and that these changes clearly exceed those found after jejunal resection alone. |
| Cholesterol absorption and synthesis during pravastatin, gemfibrozil and their combination Vanhanen, H. T. and T. A. Miettinen (1995), Atherosclerosis 115(2): 135-46. Abstract: The study evaluates cholesterol metabolism off and on treatment with pravastatin (P), gemfibrozil (G) and their combination (PG) in 38 middle-age hyperlipidemic primary care patients with serum cholesterol > 6 mmol/l and serum triglycerides < 4 mmol/l after a low-fat low-cholesterol diet. The subjects were randomized to P (40 mg/g), G (1200 mg/day), PG (40 + 1200 mg/day) or placebo for 12 weeks. We analyzed serum lipids, apolipoproteins A-I, B and E, serum cholesterol precursors (markers of cholesterol synthesis), serum plant sterols and cholestanol (markers of cholesterol absorption) and cholesterol metabolism by the sterol balance technique and cholesterol absorption efficiency. P alone or in combination with G lowered apoprotein E concentration, and serum cholesterol levels by inhibiting cholesterol synthesis measured by the precursor/cholesterol proportions with inconsistent change in fecal output of cholesterol. G alone decreased bile acid synthesis and increased biliary cholesterol secretion which were associated with reduced cholesterol absorption efficiency and the serum plant sterol and cholestanol proportions, and increased synthesis of cholesterol as measured both by the sterol balance technique and the precursor sterol proportions. A combination of PG also lowered LDL cholesterol similarly but triglyceride-rich lipoproteins significantly more than P alone, and otherwise inhibited the changes caused by G in cholesterol metabolism except that the precursor sterol proportions still indicated reduced cholesterol synthesis. Overall, the changes of the cholesterol precursor proportions were negatively related to that of cholesterol absorption efficiency and positively to that of cholesterol synthesis. The respective plant sterol and cholestanol values correlated oppositely to cholesterol absorption efficiency and synthesis. Serum precursor sterols reflected changes in cholesterol synthesis more sensitively than the sterol balance technique, even though only the latter method can quantitate cholesterol synthesis. |
| Cholesterol absorption and synthesis related to low density lipoprotein metabolism during varying cholesterol intake in men with different apoE phenotypes Gylling, H. and T. A. Miettinen (1992), J Lipid Res 33(9): 1361-71. Abstract: The aim of the present study was, first, to investigate whether cholesterol (C) absorption, enhanced by cholesterol feeding, was related to synthesis of cholesterol, serum level of low density lipoprotein (LDL)-C, and receptor activity for LDL apolipoprotein (apo) B in healthy men. Secondly, we were interested in whether apolipoprotein E (apoE) phenotypes contributed to cholesterol and LDL apoB metabolism under these conditions. We studied 29 home-living men aged 55 +/- 1 (mean +/- SE) years on a low-fat, low cholesterol (208 +/- 13 mg/day) diet followed by a low-fat high cholesterol (878 +/- 38 mg/day) diet during 5 weeks. Cholesterol feeding increased total cholesterol, LDL-C, high density lipoprotein (HDL)-C, and LDL apoB levels from 10% to 13% (P less than 0.05) and bile acid production and cholesterol turnover by 16% (P less than 0.05), decreased the fractional catabolic rate (FCR) for LDL apoB by 10% (P less than 0.05) and cholesterol absorption efficiency by 8% (P less than 0.05), while cholesterol synthesis only tended to decrease. During the cholesterol feeding, LDL-C was positively related to apoB production rate and cholesterol absorption efficiency (P less than 0.05), and negatively related to bile acid and cholesterol synthesis (P less than 0.05) and FCR for LDL apoB, which, in turn, was negatively related to cholesterol absorption efficiency and positively to bile acid synthesis. ApoE phenotype was positively related to TC, LDL-C, and LDL apoB levels and negatively to FCR for LDL apoB. The increase of the LDL-C level by the high cholesterol intake was positively correlated with LDL-C on high cholesterol diet and apoE phenotypes, so that the increase was 7% in apoE2 (ns), 11% in apoE3 (P less than 0.05), and 18% in apoE4 (P less than 0.05); the increase of bile acid synthesis was significant only in subjects with apoE2. Moreover, the increase of LDL-C was positively related to the absolute amount of dietary cholesterol absorbed and negatively to FCR for LDL apoB. The findings suggest that the higher the LDL-C level, the higher is the absorption efficiency of cholesterol and production of LDL apoB, and the lower is the removal of LDL apoB and synthesis of both bile acids and cholesterol, and the more frequently the subjects had epsilon 4 allele. The nonresponsiveness to dietary cholesterol was dependent on low LDL-C level, apoE2 phenotype, and effective bile acid synthesis.(ABSTRACT TRUNCATED AT 400 WORDS) |
| Cholesterol absorption and the metabolic syndrome: a new look at an old area Berglund, L. and D. Hyson (2003), Arterioscler Thromb Vasc Biol 23(8): 1314-6. |
| Cholesterol absorption by the gall bladder Ross, P. E., A. N. Butt, et al. (1990), J Clin Pathol 43(7): 572-5. Abstract: Model and real biles were used to investigate factors influencing cholesterol and dextran (70,000 molecular weight) absorption by the gall bladder. Cholesterol absorption was proportional to cholesterol concentration when real bile was used, but model biles showed maximal absorption at cholesterol saturation. Reduction of temperature reduced cholesterol absorption and serosal secretion, but had little effect on dextran absorption. This indicates differences in uptake where cholesterol undergoes passive diffusion but dextran is taken up by fluid-phase endocytosis. Model bile prepared with a single bile salt showed lowest cholesterol uptake from cholate bile, but there was no difference in serosal secretion. Dextran uptake was also lowest from cholate bile, although serosal secretion was highest. These results show that an increase in the biliary content of dihydroxy bile salts increases gall bladder permeability to both hydrophobic and hydrophilic molecules and may lead to the accumulation of lipids in the mucosa, as seen in cholesterolosis. |