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MeSH: cholesterol-7-alfa-hydroxylasa-metabolismus

8 záznamů v PubMed Filtry

Článek

Evaluation of probiotic bifidobacteria strains from Iranian traditional dairy products for their anti-hyperlipidemic potential

Afshar, Nasim
Autor Afshar, Nasim Department of Microbiology, Faculty of Sciences, Arak Branch, Islamic Azad University, Arak, Iran
Amini, Kumarss
Autor Amini, Kumarss ORCID Department of Microbiology, Faculty of Sciences, Saveh Branch, Islamic Azad University, Saveh, Iran. dr_kumarss_amini@yahoo.com
Mohajerani, Hamidreza
Autor Mohajerani, Hamidreza Department of Biology, Arak Branch, Islamic Azad University, Arak, Iran
Saki, Sasan
Autor Saki, Sasan Department of Medical Laboratory Sciences, Faculty of Medical Sciences, Arak Branch, Islamic Azad University, Arak, Iran

Folia microbiologica. 2024 Aug ; 69 (4) : 875-887. [epub] 20240110

Folia Microbiol (Praha)
ISSN 1874-9356 | 0015-5632
Zdroj

This study investigated the therapeutic potential of probiotic bifidobacteria, isolated from Iranian fermented dairy products, in a hyperlipidemic animal model. Bifidobacterium strains were extracted from traditional dairy samples and screened using physiological and phenotypic examinations, 16S rRNA analysis, and probiotic properties such as tolerance to gastrointestinal juice, antimicrobial activity, and antibiotic susceptibility. The ability of the screened bifidobacteria to reduce serum and liver lipids in vivo was tested using male Wistar rats. Six strains of bifidobacteria were isolated from traditional Iranian fermented dairy. These strains showed promising in vitro activity in lowering triglyceride and cholesterol, tolerance to simulated gastrointestinal juice, the ability to adhere to Caco-2 cells, acceptable antibiotic susceptibility, and a broad spectrum of antibacterial activity. The diet supplemented with isolated bifidobacteria significantly reduced serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), liver tissue lipid levels, and hepatic enzymes in animals when compared to a high-fat diet without strains (p < 0.01). Additionally, the potential probiotic-supplemented diet significantly increased bile acid excretion in the feces and upregulated hepatic CYP7A1 expression levels (p < 0.05), while NPC1L1, ACAT2, and MTP gene expressions in small intestinal cells were downregulated (p < 0.05). Bifidobacteria isolated from Iranian traditional dairy showed potential for use in the production of fermented foods that have hypolipemic activity in the host.

Klíčová slova
Bifidobacteria, Cholesterol-lowering, Probiotics, Triglyceride-lowering,
MeSH
antibakteriální látky farmakologie MeSH
Bifidobacterium * genetika izolace a purifikace metabolismus MeSH
Caco-2 buňky MeSH
cholesterol-7-alfa-hydroxylasa genetika metabolismus MeSH
cholesterol krev metabolismus MeSH
feces mikrobiologie MeSH
hyperlipidemie * MeSH
játra metabolismus MeSH
krysa rodu Rattus MeSH
lidé MeSH
mléčné výrobky mikrobiologie MeSH
modely nemocí na zvířatech MeSH
potkani Wistar * MeSH
probiotika * aplikace a dávkování farmakologie MeSH
RNA ribozomální 16S genetika MeSH
triglyceridy krev metabolismus MeSH
žlučové kyseliny a soli metabolismus MeSH
zvířata MeSH
Check Tag
krysa rodu Rattus MeSH
lidé MeSH
mužské pohlaví MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
Geografické názvy
Írán MeSH
Názvy látek
antibakteriální látky MeSH
cholesterol-7-alfa-hydroxylasa MeSH
cholesterol MeSH
RNA ribozomální 16S MeSH
triglyceridy MeSH
žlučové kyseliny a soli MeSH

Článek

The effect of colesevelam treatment on bile acid and lipid metabolism and glycemic control in healthy men

Physiological research. 2016 Dec 13 ; 65 (6) : 995-1003. [epub] 20160819

Physiol Res
ISSN 1802-9973 | 0862-8408
Zdroj

The treatment of hypercholesterolemia with bile acid (BA) sequestrants results in upregulation of BA synthesis through the classical pathway initiated by cholesterol 7alpha-hydroxylase (CYP7A1). To characterize the detailed dynamics of serum lipid and BA concentrations and the BA synthesis rate in response to treatment with BA sequestrants and to determine whether the -203A/C promoter polymorphism of the CYP7A1 encoding gene (CYP7A1) affects such a response, this pilot study was carried out in healthy men (8 homozygous for the -203A allele and 8 homozygous for the -203C allele of CYP7A1). The subjects were treated for 28 days with colesevelam and blood was drawn for analysis before and on days 1, 3, 7, 14 and 28 of treatment. The response of lipids, BA, fibroblast growth factor-19 (FGF19) and 7alpha-hydroxy-4-cholesten-3-one (C4) to colesevelam did not differ between carriers of -203A and -203C alleles; their data were then aggregated for further analysis. Colesevelam treatment caused immediate suppression of FGF19 concentration and a fivefold increase in CYP7A1 activity, as assessed from C4 concentration, followed by a 17 % decrease in LDL-cholesterol. Although total plasma BA concentrations were not affected, the ratio of cholic acid/total BA rose from 0.25+/-0.10 to 0.44+/-0.16 during treatment at the expense of decreases in chenodeoxycholic and deoxycholic acid.

Článek

Diurnal variation in cholesterol 7α-hydroxylase activity is determined by the -203A>C polymorphism of the CYP7A1 gene

Croatian medical journal. 2016 Apr 23 ; 57 (2) : 111-7.

Croat Med J
ISSN 1332-8166 | 0353-9504
Zdroj

AIM: To determine whether the promoter polymorphism -203A>C of cholesterol-7α-hydroxylase encoding gene (CYP7A1) affects diurnal variation in CYP7A1 enzyme activity. METHODS: The study included 16 healthy male volunteers - 8 homozygous for -203A and 8 homozygous for the -203C allele of CYP7A1. Three 15-hour examinations (from 7am to 10pm) were carried out for each of the participants: after one-day treatment with cholestyramine; after one-day treatment with chenodeoxycholic acid (CDCA); and a control examination without any treatment. The plasma concentration of 7α-hydroxy-4-cholesten-3-one (C4), a marker of CYP7A1 activity, was determined in all the experiments at 90-min intervals. RESULTS: CYP7A1 activity was up-regulated after treatment with cholestyramine and suppressed after treatment with CDCA. There were no differences between -203A and -203C allele carriers in the response of enzyme activity to both drugs. In the control experiment, -203A allele carriers displayed diurnal variation in enzyme activity, whereas CYP7A1 activity did not change in -203C allele carriers. These results were confirmed by modeling the dynamics of C4 using polynomial regression. CONCLUSION: The promoter polymorphism of the CYP7A1 gene has a pronounced impact on diurnal variation in CYP7A1 activity.

MeSH
aktivace enzymů MeSH
cholestenony krev MeSH
cholesterol-7-alfa-hydroxylasa genetika metabolismus MeSH
cholesterol krev MeSH
cirkadiánní rytmus fyziologie MeSH
dospělí MeSH
lidé MeSH
plocha pod křivkou MeSH
polymorfismus genetický * MeSH
promotorové oblasti (genetika) MeSH
upregulace MeSH
žlučové kyseliny a soli biosyntéza MeSH
Check Tag
dospělí MeSH
lidé MeSH
mužské pohlaví MeSH
Publikační typ
časopisecké články MeSH
Názvy látek
7 alpha-hydroxy-4-cholesten-3-one MeSH Prohlížeč
cholestenony MeSH
cholesterol-7-alfa-hydroxylasa MeSH
cholesterol MeSH
CYP7A1 protein, human MeSH Prohlížeč
žlučové kyseliny a soli MeSH

Článek

Improvement bioavailability of silymarin ameliorates severe dyslipidemia associated with metabolic syndrome

Xenobiotica; the fate of foreign compounds in biological systems. 2015 ; 45 (9) : 751-6. [epub] 20150716

Xenobiotica
ISSN 1366-5928 | 0049-8254
Zdroj

1. To compare the effectiveness of different drug forms of silymarin: standardized extract of silymarin (SS), micronized silymarin (MS) and silymarin in the form of phytosome (PS) on dyslipidemia and liver fat accumulation in a model of metabolic syndrome, in non-obese hereditary hypertriglyceridemic rats. The second aim of this study was to slightly uncover the silymarin action on enzymes and proteins involved in cholesterol metabolism and excretion. 2. Silymarin administered to hereditary hypertriglyceridemic rats as dietary supplements (1%) for 4 weeks significantly lowered the plasma levels of triglycerides, total cholesterol and markedly increased HDL cholesterol level. Western blot analyses showed significant increase in the protein expression of CYP7A1 and CYP4A and increase in protein expression of selected ABC transporters. Silymarin in the form of phytosome and micronized silymarin were more effective forms of silymarin. 3. These findings suggest that silymarin may favorably affect the metabolism of cholesterol and triglycerides in rats with metabolic syndrome. Raising HDL levels suggests potentially important anti-atherogenic effect of silymarin. The changes in expression of cytochromes P450 and ABC transporters involved in cholesterol metabolism and excretion could be partially responsible for the hypolipidemic effect of silymarin.

Klíčová slova
ABC transporters, CYP4A, CYP7A1, HDL-cholesterol,
MeSH
ABC transportéry metabolismus MeSH
biologická dostupnost MeSH
cholesterol-7-alfa-hydroxylasa metabolismus MeSH
cytochrom P450 CYP4A metabolismus MeSH
dyslipidemie krev komplikace farmakoterapie MeSH
játra účinky léků enzymologie MeSH
lipidy krev MeSH
metabolický syndrom krev komplikace farmakoterapie MeSH
potkani Wistar MeSH
silymarin farmakologie terapeutické užití MeSH
western blotting MeSH
zvířata MeSH
Check Tag
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Názvy látek
ABC transportéry MeSH
cholesterol-7-alfa-hydroxylasa MeSH
CYP7A1 protein, rat MeSH Prohlížeč
cytochrom P450 CYP4A MeSH
lipidy MeSH
silymarin MeSH

Článek

Cholestatic effect of epigallocatechin gallate in rats is mediated via decreased expression of Mrp2

Toxicology. 2013 Jan 07 ; 303 () : 9-15. [epub] 20121110

ISSN 1879-3185 | 0300-483X
Zdroj

Epigallocatechin gallate (EGCG) has been shown to be protective in various experimental models of liver injury, although opposite effects have also been reported. Since its effect on biliary physiology has not been thoroughly investigated, the present study evaluated effect of EGCG on bile flow and bile acid homeostasis in rats. Compared to controls, EGCG treatment decreased bile flow by 23%. Hepatic paracellular permeability and biliary bile acid excretion were not altered by EGCG administration, but biliary glutathione excretion was reduced by 70%. Accordingly, the main glutathione transporter on the hepatocyte canalicular membrane, multidrug resistance-associated protein 2 (Mrp2), was significantly decreased at the protein level. EGCG administration also doubled plasma bile acid levels compared to controls. While protein levels of the main hepatic bile acid transporters were unchanged, the rate-limiting enzyme in the bile acid synthesis, Cyp7a1, was significantly increased by EGCG. Enhanced bile acid synthesis in these animals was also confirmed by a 2-fold increase in plasma marker 7α-hydroxy-4-cholesten-3-one. In contrast, EGCG markedly downregulated major bile acid transporters (Asbt and Ostα) and regulatory molecules (Shp and Fgf15) in the ileum. When EGCG was coadministered with ethinylestradiol, a potent cholestatic agent, it did not show any additional effect on the induced cholestasis. This study shows ability of EGCG to raise plasma bile acid concentrations, mainly through Cyp7a1 upregulation, and to decrease bile production through reduction in Mrp2-mediated bile acid-independent bile flow. In conclusion, our data demonstrate that under certain conditions EGCG may induce cholestasis.

Článek

Regulation of diurnal variation of cholesterol 7alpha-hydroxylase (CYP7A1) activity in healthy subjects

Physiological research. 2010 ; 59 (2) : 233-238. [epub] 20090619

Physiol Res
ISSN 0862-8408
Zdroj

Cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory enzyme of bile acid synthesis, displays a pronounced diurnal variation. To better understand the regulation of CYP7A1 activity, three day-long examinations were carried out in 12 healthy men. The concentrations of 7alpha-hydroxycholest-4-en-3-one (C4), a surrogate marker of CYP7A1 activity, bile acids (BA), insulin, glucose, nonesterified fatty acids, triglycerides, and cholesterol were measured in serum in 90-min intervals from 7 AM till 10 PM. To lower and to increase BA concentration during the study, the subjects received cholestyramine and chenodeoxycholic acid (CDCA), respectively, in two examinations. No drug was used in the control examination. There was a pronounced diurnal variation of C4 concentration with a peak around 1 PM in most of the subjects. The area under the curve (AUC) of C4 concentration was five times higher and three times lower when subjects were treated with cholestyramine and CDCA, respectively. No relationship was found between AUC of C4 and AUC of BA concentration, but AUC of C4 correlated positively with that of insulin. Moreover, short-term treatment with cholestyramine resulted in about 10 % suppression of glycemia throughout the day. Our results suggest that insulin is involved in the regulation of diurnal variation of CYP7A1 activity in humans.

Článek

Differences in expression of cholesterol 7alpha-hydroxylase between PHHC and Wistar rats

Folia biologica. 2008 ; 54 (1) : 18-23.

Folia Biol (Praha)
ISSN 0015-5500
Zdroj

PHHC rats represent a suitable experimental model of polygenic hypercholesterolemia. It has been found that its metabolic defect is not related to alimentary cholesterol absorption and LDL clearance. We have tested possible changes in cholesterol clearance from the liver to bile acids by analysis of the expression of the cholesterol 7alpha-hydroxylase (cyp7A1) gene in PHHC (N = 20) and Wistar (controls) (N = 19) male rats. The animals were fed standard laboratory diet (CD) or control diet containing 5% fat and 2% cholesterol (HCD) for two weeks. SSCP and RT-PCR were used for mutation analysis and study of gene expression, respectively. Although the basal cholesterolemia in PHHC was similar to controls (1.80 +/- 0.48 and 1.52 +/- 0.39 mmol/l, respectively), it rose in rats fed on HCD to 9.81 +/- 1.65 mmol/l in PHHC rats and only to 2.19 +/- 0.41 mmol/l in controls. Similarly to the basal cholesterol concentration, the gene expression of cyp7A1 in the liver of rats on CD was the same in both compared groups on the control diet. In controls on HCD, cyp7A1 gene expression increased almost 4-fold immediately on the first day and achieved up to approximately 20-multiple basal expression in the end of the feeding period. Compared to the controls, after switching to HCD the cyp7A1 gene expression in PHHC rats did not change dramatically. These results suggest that the cyp7A1 gene plays an important role in development of hypercholesterolemia in PHHC rats.