scholarly journals Antioxidant Supplements Improve Profiles of Hepatic Oxysterols and Plasma Lipids in Butter-fed Hamsters

2010 ◽  
Vol 3 ◽  
pp. NMI.S3911 ◽  
Author(s):  
Johanne Poirier ◽  
Kevin A. Cockell ◽  
W.M. Nimal Ratnayake ◽  
Kylie A. Scoggan ◽  
Nick Hidiroglou ◽  
...  

Hypercholesterolemia diets are associated with oxidative stress that may contribute to hypercholesterolemia by adversely affecting enzymatically-generated oxysterols involved in cholesterol homeostasis. An experiment was conducted to examine whether the cholesterol-lowering effects of the antioxidants selenium and α-tocopherol were related to hepatic oxysterol concentrations. Four groups of male Syrian hamsters (n = 7-8) were fed high cholesterol and saturated fat (0.46% cholesterol, 14.3% fat) hypercholesterolemic semi-purified diets: 1) Control; 2) Control + α-tocopherol (67 IU all-racemic-α-tocopheryl-acetate/kg diet); 3) Control + selenium (3.4 mg selenate/kg diet); and 4) Control + α-tocopherol + selenium. Antioxidant supplementation was associated with lowered plasma cholesterol concentrations, decreased tissue lipid peroxidation and higher hepatic oxysterol concentrations. A second experiment examined the effect of graded selenium doses (0.15, 0.85, 1.7 and 3.4 mg selenate/kg diet) on mRNA expression of the oxysterol-generating enzyme, hepatic 27-hydroxylase (CYP27A1, EC 1.14.13.15), in hamsters (n = 8-9) fed the hypercholesterolemic diets. Supplementation of selenium at 3.4 mg selenate/kg diet was not associated with increased hepatic 27-hydroxylase mRNA. In conclusion, the cholesterol lowering effects of selenium and α-tocopherol were associated with increased hepatic enzymatically generated oxysterol concentrations, which appears to be mediated via improved antioxidant status rather than increased enzymatic production.

2010 ◽  
Vol 104 (3) ◽  
pp. 364-373 ◽  
Author(s):  
Tina Immerstrand ◽  
Kristina E. Andersson ◽  
Caroline Wange ◽  
Ana Rascon ◽  
Per Hellstrand ◽  
...  

In the present study, we evaluated the cholesterol-lowering effects of different oat bran (OB) preparations, differing regarding their peak molecular weight (MWp) of β-glucans (2348, 1311, 241, 56, 21 or < 10 kDa), in C57BL/6NCrl mice. The diets were designed to be atherogenic (0·8 % cholesterol and 0·1 % cholic acid), and they reflected the Western diet pattern (41 % energy fat). All OB preparations that were investigated significantly reduced plasma cholesterol when compared with a cellulose-containing control diet, regardless of the molecular weight of β-glucan. Moreover, the difference in viscous properties between the processed OB (from 0·11 to 17·7 l/g) did not appear to play a major role in the cholesterol-lowering properties. In addition, there was no correlation between the molecular weight of β-glucan and the amount of propionic acid formed in caecum. Interestingly, however, there was a significant correlation between the ratio of (propionic acid+butyric acid)/acetic acid and the MWpof β-glucans: the ratio increased with increasing molecular weight. The results of the present study suggest that the molecular weights and viscous properties of β-glucan in oat products may not be crucial parameters for their cholesterol-lowering effects.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Li Zhang ◽  
Prashant Rajbhandari ◽  
Christina Priest ◽  
Jaspreet Sandhu ◽  
Xiaohui Wu ◽  
...  

Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show that RNF145 triggers ubiquitination of SCAP on lysine residues within a cytoplasmic loop essential for COPII binding, potentially inhibiting its transport to Golgi and subsequent processing of SREBP-2. These findings define an additional mechanism linking hepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR pathways.


1989 ◽  
Vol 53 (6) ◽  
pp. 1647-1652 ◽  
Author(s):  
Kimio SUGIYAMA ◽  
Akio OHISHI ◽  
Yukari OHNUMA ◽  
Keiichiro MURAMATSU

2011 ◽  
Vol 108 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Johanne Poirier ◽  
Kevin A. Cockell ◽  
Kylie A. Scoggan ◽  
W. M. Nimal Ratnayake ◽  
Hélène Rocheleau ◽  
...  

The aim of the present study was to elucidate possible cholesterol-lowering mechanism(s) of high-dose supplemental Se in the form of selenite, a known hypocholesterolaemic agent. Male Syrian hamsters (four groups, ten per group) were fed semi-purified diets for 4 weeks containing 0·1 % cholesterol and 15 % saturated fat with selenite corresponding to varying levels of Se: (1) Se 0·15 parts per million (ppm), control diet; (2) Se 0·85 ppm; (3) Se 1·7 ppm; (4) Se 3·4 ppm. Lipids were measured in the bile, faeces, liver and plasma. The mRNA expression of several known regulators of cholesterol homeostasis (ATP-binding cassette transporters g5 (Abcg5) and g8 (Abcg8), 7-hydroxylase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, LDL receptor (LdLr) and Nieman-Pick C1-like 1 protein (Npc1l1)) were measured in the liver and/or jejunum. Oxysterols including 24-(S)-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol (27-OHC) were measured in the liver. Significantly lower total plasma cholesterol concentrations were observed in hamsters consuming the low (0·85 ppm) and high (3·4 ppm) Se doses. The two highest doses of Se resulted in decreased plasma LDL-cholesterol concentrations and increased mRNA levels of hepatic Abcg8, Ldlr and jejunal Ldlr. Higher hepatic 27-OHC and TAG concentrations and lower levels of jejunal Npc1l1 mRNA expression were noted in the 1·7 and 3·4 ppm Se-treated hamsters. Overall, Se-induced tissue changes in mRNA expression including increased hepatic Abcg8 and Ldlr, increased jejunal Ldlr and decreased jejunal Npc1l1, provide further elucidation regarding the hypocholesterolaemic mechanisms of action of Se in the form of selenite.


1990 ◽  
Vol 63 (3) ◽  
pp. 547-552 ◽  
Author(s):  
Shanthi Mendis ◽  
Ravi Kumarasundaram

The present paper reports the influence on plasma lipids of isoenergetic diets containing 30 YO of energy as fat, with a polyunsaturated: saturated fat ratio of 4.00 or 0.25, consumed for 8 weeks by twenty-five young normolipidaemic males. Approximately 70 % of the fat energy was provided by the test fats: soya-bean fat and coconut fat. During the soya-bean-fat-eating period the total plasma cholesterol level fell significantly compared with baseline values (P< 0.001) and during the coconut-fat-eating phase total plasma cholesterol level increased significantly compared with the soya-bean-eating period (P< 0001).On the soya-bean-fat diet, high-density-lipoprotein (HDL)-cholesterol decreased by 15 YO (range 6–35 YO) and plasma triacylglycerols decreased by 25 YO (range 13–37 YO). Results of the present study show that even when the proportion of total fat in the diet is low, a high intake of linoleic acid lowers both total plasma cholesterol and HDL-cholesterol, while a high intake of saturated fat elevates both these lipid fractions. Application of regression formulas to the present findings indicates that short-chain saturated fatty acids have a neutral effect on serum cholesterol


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Yuguang Lin ◽  
Mario A. Vermeer ◽  
Elke A. Trautwein

Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols.


2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Line Zurkinden ◽  
Dmitri Sviridov ◽  
Bruno Vogt ◽  
Geneviève Escher

Sterol 27-hydroxylase (CYP27A1) catalyzes the hydroxylation of cholesterol to 27-hydroxycholesterol (27-OHC) and regulates cholesterol homeostasis. In Cyp27a1/ Apolipoprotein E (ApoE) double knockout (KO) mice fed with Western diet (WD), the atherosclerotic phenotype found in ApoE KO mice was reversed. As protective mechanism, up-regulation of Cyp3a11 and Cyp7a1 was proposed. Cyp27a1 heterozygote/ApoE KO (het) mice, with reduced Cyp27a1 expression and normal levels of Cyp7a1 and Cyp3a11, developed more severe lesions than ApoE KO mice. To analyze the contribution of Cyp3a11 to the protection of atherosclerosis development, Cyp3a11 was induced by Rifampicin (RIF) in ApoE KO and het mice. Males were fed with WD and treated daily with RIF (10 mg/kg ip) or vehicle for 4 weeks. Atherosclerosis was quantified in the aortic valve. Plasma lipids and 27-hydroxycholesterol (27-OHC), expression of cytochromes P450 and genes involved in cholesterol transport and bile acids (BAs) signaling in liver and intestine, and intestinal cholesterol absorption were analyzed. RIF increased expression of hepatic but not intestinal Cyp3a11 4-fold in both genotypes. In ApoE KO mice treated with RIF, we found a 2-fold decrease in plasma cholesterol, and a 2-fold increase in high-density lipoprotein/low-density lipoprotein ratio and CY27A1 activity. Intestinal cholesterol absorption remained unchanged and atherosclerotic lesions decreased approximately 3-fold. In het mice, RIF had no effect on plasma lipids composition, CYP27A1 activity, and atherosclerotic plaque development, despite a reduction in cholesterol absorption. In conclusion, the antiatherogenic effect of Cyp3a11 induction by RIF was also dependent on Cyp27a1 expression.


PEDIATRICS ◽  
1980 ◽  
Vol 65 (4) ◽  
pp. 727-734
Author(s):  
John A. Morrison ◽  
Rhea Larsen ◽  
Lenora Glatfelter ◽  
Donna Boggs ◽  
Kathryn Burton ◽  
...  

Relationships between nutrient intakes and plasma lipids and lipoproteins were studied in 1,669 schoolchildren, aged 6 to 19 years; 948 were selected by random recall and 721 because of elevated plasma cholesterol or triglyceride (hyperlipidemic recall). Nutrient intake data was collected by using a 24-hour dietary recall. Median dietary cholesterol intakes for 6 to 9-year-old boys and girls in the random recall group were 222 and 230 mg/day, with polyunsaturated/saturated fat ratios of 0.34 and 0.33. For boys and girls, aged 10 to 12 years, median dietary cholesterol intakes were 296 and 235 mg/day, for 13 to 15 year olds, 343 and 237, and for 16 to 19 year olds, 418 and 221 mg/day. The dietary polyunsaturated/saturated fat ratios did not change appreciably with age. Partial correlation coefficients describing relationships between lipids, lipoproteins, and nutrients after adjustment for age, sex, race, and Quetelet index (W/H2) were calculated for all children (random and hyperlipidemic recall) after excluding children having plasma cholesterol, triglycerides, and calories less than or equal to the first or greater than or equal to the 99th percentiles for the random recall children. Plasma cholesterol was inversely and triglyceride positively correlated with dietary sucrose. Plasma low density lipoprotein cholesterol was inversely correlated with the dietary polyunsaturated/saturated fat ratio, total carbohydrate, and sugar. Potential relationships between nutrients and lipids-lipoproteins were also examined in children having low (first to tenth percentile), intermediate (45th to 55th percentile), and high (90th to 99th percentile) nutrient intake, after covariance adjustment for age, race, sex, and Quetelet index. Total plasma cholesterol fell as sucrose intake increased. Triglyceride rose along with caloric intake, total carbohydrate intake, and sucrose intake, while high density lipoprotein cholesterol levels fell with increasing caloric and sucrose intake. As dietary polyun-saturate ingestion rose from low to intermediate to high, plasma low density lipoprotein cholesterol increased. Nutrient intake may play a small but significant role relative to lipids and lipoproteins in children and, as such, may have importance relative to pediatric precursors of atherosclerosis.


1989 ◽  
Vol 62 (02) ◽  
pp. 797-801 ◽  
Author(s):  
E Berg Schmidt ◽  
E Ernst ◽  
K Varming ◽  
J O Pedersen ◽  
J Dyerberg

SummaryPlasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type II a and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.


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