BACKGROUND/OBJECTIVES: The purpose of the current study was to investigate the effect of red pericarp glutinous rice rich in polyphenols (Jakwangchalbyeo, red rice) on serum and hepatic levels of cholesterol and hepatic protein expression linked to synthesis and degradation of cholesterol in a hypercholesterolemic mice diet as compared with brown rice. MATERIALS/METHODS: C57BL/6 male mice were randomly divided into four groups (n = 5 each), which were fed different diets for a period of 12 weeks: American Institute of Nutrition (AIN)-93G diet, AIN-93G diet with 2% cholesterol, brown rice with 2% cholesterol, or red rice with 2% cholesterol. RESULT: Consumption of red rice resulted in a significant decrease in serum level of low-density lipoprotein cholesterol and hepatic levels of triglyceride and total-cholesterol. Expression of acyl-coenzyme A cholesterol acyltransferase-2 (ACAT-2), sterol regulatory element binding protein-2 (SREBP-2), and 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase was decreased, while expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK)/AMPK ratio, cholesterol 7-alpha-hydroxylase (CYP7a1), and sterol 12-alpha-hydroxylase (CYP8b1) was increased in mice fed red rice. Brown rice had similar effects on cholesterol metabolism, but the effect of red rice was significantly greater than that of brown rice. CONCLUSIONS: The current study suggested that red rice had a hypocholesterolemic effect by lowering hepatic cholesterol synthesis through ACAT-2, HMG-CoA reductase, and SREBP-2, and by enhancing hepatic cholesterol degradation through CYP7a1 and CYP8b1 in mice fed a hypercholesterolemic diet.
Adenosine Monophosphate ; Animals ; Cholesterol 7-alpha-Hydroxylase ; Cholesterol* ; Coenzyme A ; Diet* ; Humans ; Lipoproteins ; Liver ; Male ; Metabolism* ; Mice* ; Oxidoreductases ; Phenol* ; Polyphenols ; Protein Kinases ; Steroid 12-alpha-Hydroxylase ; Triglycerides

Apolipoproteins E ; genetics ; physiology ; Cholesterol 7-alpha-Hydroxylase ; genetics ; Cholesterol, LDL ; genetics ; Coronary Disease ; genetics ; Genetic Predisposition to Disease ; genetics ; Genetic Variation ; Humans ; Polymorphism, Genetic

The present study was performed to elucidate the hypocholesterolemic action of chitosan on the diet-induced hypercholesterolemia in rats. Male Sprague-Dawley rats (n=24) were fed with chitosan-free diet (Control), diets containing 2% or 5% chitosan for 4 weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Body weight gain and food intake of rats did not differ among the groups. The chitosan treated groups showed significant improvement in the plasma concentration of total cholesterol and LDL-cholesterol compared to the control group (p<0.05). Also, the chitosan treated groups decreased the liver concentration of total lipid and total cholesterol compared to the control group (p<0.05). The activity of hepatic cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids, was increased by 123% and 165% for the 2% or 5% chitosan diets, respectively. These findings suggest that enhancement of hepatic CYP7A1 activity may be a mechanism, which can partially account for the hypocholesterolemic effect of dietary chitosan in cholesterol metabolism.
Animals ; Bile Acids and Salts ; Body Weight ; Chitosan* ; Cholesterol 7-alpha-Hydroxylase ; Cholesterol* ; Cholic Acid ; Diet ; Eating ; Humans ; Hypercholesterolemia* ; Liver* ; Male ; Metabolism ; Plasma* ; Rats* ; Rats, Sprague-Dawley

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6), "Guanyuan" (CV 4) and "Zusanli" (ST 36) on CYP7A1 expression in liver of rabbits with atherosclerosis (AS), and to explore the mechanism of acupuncture for prevention and treatment of atherosclerosis. METHODS: A total of 26 male rabbits were adaptively fed for 1 week in different cages. Seven rabbits were randomly divided into a blank group, and the remaining 19 rabbits were divided into a model group. The blank group was fed with normal diet, while the model group was fed with high-fat diet. After high-fat diet for 4 weeks, the rabbits in the model group were treated with balloon injury surgery of the common carotid artery; after surgery, the rabbits were fed with high-fat diet for 4 weeks. One rabbit was randomly selected from the blank group and model group to obtain the pathological section of carotid artery; the HE staining was used to observe the pathomorphology of atheromatous plaque to determine the success of modeling or not. After successful establishment of modeling, 18 rabbits were randomly divided into a AS model group, an EA group and a medication group, 6 rabbits in each one. The rabbits in the AS model group received no treatment; the rabbits in the medication group were treated with intragastric administration of atorvastatin calcium tablets; the rabbits in the EA group were treated with EA at "Neiguan" (PC 6), "Guanyuan" (CV 4) and "Zusanli" (ST 36), once a day, 20 min per treatment; six-day EA treatment constituted one course, and totally 4 courses were given with an interval of 1 day between courses. After treatment, vein blood was collected from rabbit ear, and cholesterol (CHO), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured in each group; the CYP7A1 protein expression in rabbit liver was measured by Western blot method, and CYP7A1 mRNA expression in rabbit liver was measured by RT-PCR. RESULTS: Compared with the blank group, the contents of CHO, TG and LDL in the AS model group were significantly increased, but HDL was significantly decreased, and the expression of CYP7A1 protein and CYP7A1 mRNA in the liver were significantly decreased (all <0.01). After treatment, compared with the model group, the contents of CHO, TG and LDL in the EA group and medication group were significantly reduced, but HDL was significantly increased, and the expression of CYP7A1 protein and CYP7A1 mRNA in the liver were significantly increased (all <0.01). The significant difference of each outcome between the EA group and medication group was not observed (all >0.05). CONCLUSION EA could significantly improve blood lipid and promote the expression of CYP7A1 mRNA in rabbits with atherosclerotic, which may be one of the mechanisms of EA for atherosclerosis.
Acupuncture Points ; Animals ; Atherosclerosis ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; metabolism ; Electroacupuncture ; Humans ; Liver ; Male ; Rabbits ; Random Allocation ; Rats, Sprague-Dawley ; Triglycerides

BACKGROUNDGenetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7alpha-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism.

METHODSOur study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used.

RESULTSThe results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.

CONCLUSIONOur results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.

Adult ; Aged ; Alleles ; Apolipoproteins E ; genetics ; Cholesterol 7-alpha-Hydroxylase ; genetics ; Cholesterol, LDL ; blood ; Coronary Disease ; genetics ; Female ; Genetic Linkage ; Genetic Variation ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, LDL ; genetics ; Risk Factors

To study the effect of cholesterol and 25-OH-cholesterol on cholesterol metabolism in HepG2 cells and the effect of coptisine (Cop) extracted from Coptidis Rhizoma (CR) in reducing and regulating cholesterol. In this study, TC, TG, LDL-c and HDL-c were measured by biochemical analysis; mRNA and protein expressions of LDLR, HMGCR and CYP7A1 were detected by qRT-PCR and Western blot. According to the results, cholesterol and 25-OH-cholesterol inducing could decrease in mRNA and protein expressions of LDLR and CYP7A1, so as to increase TC and LDL-c contents. However, Cop could up-regulate mRNA and protein expressions of LDLR and CYP7A1 and down-regulate that of HMGCR, so as to reduce TC and LDL-c levels. These findings suggested that Cop has potential pharmacological activity for reducing cholesterol, and may reduce cholesterol by regulating mRNA and protein expressions of key genes involved in cholesterol metabolism, such as LDLR, CYP7A1 and HMGCR. This study laid a firm theoretical foundation for developing new natural drugs with the cholesterol-lowering activity.
Berberine ; analogs & derivatives ; pharmacology ; Cholesterol ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Enzymologic ; drug effects ; Hep G2 Cells ; Humans ; Hydroxymethylglutaryl CoA Reductases ; genetics ; metabolism ; Receptors, LDL ; genetics ; metabolism ; Triglycerides ; metabolism

Animals ; Cholelithiasis ; genetics ; Cholesterol ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; genetics ; Genetic Predisposition to Disease ; Hydroxymethylglutaryl CoA Reductases ; genetics ; Liver ; enzymology ; Male ; Mice ; Mice, Inbred AKR ; Mice, Inbred C57BL ; Receptors, LDL ; genetics ; Sterol O-Acyltransferase ; genetics

BACKGROUND: Expression of hepatic cholesterol 7alpha-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1). METHODS: We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line RESULTS: Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor beta/retinoid X receptor alpha/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding. CONCLUSION: We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.
Animals ; Bile Acids and Salts ; Carcinoma, Hepatocellular ; Cell Line ; Child ; Child, Orphaned ; Cholesterol ; Cholesterol 7-alpha-Hydroxylase ; DNA ; Hepatocytes ; Humans ; Liver* ; Mice ; Microarray Analysis ; Real-Time Polymerase Chain Reaction ; Receptors, Thyroid Hormone ; RNA ; RNA, Messenger* ; Thyroid Gland* ; Thyroid Hormones ; Transcription Factors

OBJECTIVETo determine the physiological role of D-bifunctional protein (DBP) in bile acid biosynthesis through investigating the effect of increasing activity of DBP on bile acid biosynthesis.

METHODSTwenty male Wistar rats were divided into two groups: diethylhexyl phthalate (DEHP) group (n = 10) and control group (n = 10). Serum triglyceride, total cholesterol, hepatic DBP activity, and fecal bile acids were assayed. The mRNA levels of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha), DBP, and cholesterol 7alpha-hydroxylase (CYP7A1) were detected by RT-PCR.

RESULTSCompared with control group, serum triglyceride level was decreased significantly and PPARalphamRNA level was increased significantly in DEHP group (P < 0.01). Together with a sharp induction of DBP mRNA expression and DBP activity in DEHP group (P < 0.01), the levels of CYP7A1 mRNA and fecal bile acids were significantly increased by 1.9 times and 1.6 times respectively compared to control group (P < 0.01). There was a significantly positive correlation between DBP mRNA level or DBP activity and CYP7A1 mRNA level (r = 0.89, P < 0.01; r = 0.95, P < 0.01).

CONCLUSIONThe up-regulation of DBP mRNA and activity in liver can result in the increase in CYP7A1 mRNA expression and bile acid biosynthesis, suggesting that DBP may be involved in bile acid biosynthesis together with CYP7A1.

17-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Bile Acids and Salts ; biosynthesis ; Cholesterol 7-alpha-Hydroxylase ; analysis ; Enoyl-CoA Hydratase ; metabolism ; Liver ; metabolism ; Male ; Multienzyme Complexes ; metabolism ; PPAR alpha ; analysis ; Peroxisomal Multifunctional Protein-2 ; RNA, Messenger ; analysis ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo investigate the expressions of small heterodimer partner (SHP) and target gene cholesterol-7-hydroxylase (CYP7A1) in livers of rats with intrahepatic cholestasis of pregnancy (ICP), and to study the mechanism of ICP.

METHODSThirty SD rats (pregnant for 15 days) were equally and randomly divided into two groups: an estradiol benzoate (EB) group and a normal saline (NS) group. Two ml blood was drawn from each rat before and on the 5th day after medicine administration to measure the levels of ALT, AST, ALP, TBA, TBIL, and DBIL. After delivery, the histopathological changes of the mother rat livers were studied. The mRNA and protein expressions of SHP and CYP7A1 in the livers were determined by RT-PCR and Western blot.

RESULTS(1) In the EB group, the serum levels of ALT, AST, ALP, TBA, TBil, and DBil after EB administration increased significantly (P less than 0.01), but there were no significant changes in the NS group (P more than 0.05); (2) Intrahepatic cholestasis appeared in the EB group, but not in the NS group; (3) The mRNA expressions of SHP and CYP7A1 were significantly higher in the EB group than in the NS group [(SHPmRNA: NS 0.365+/-0.0317 vs EB 0.4865+/-0.0237, P less than 0.01), (CYP7A1 mRNA: NS 0.3570+/-0.0175 vs EB 0.4802+/-0.0217, P less than 0.01)]; (4) The protein expressions of SHP and CYP7A1 were also higher in the EB group than that in the NS group [(SHP: NS 0.3762+/-0.0284 vs EB 0.5033+/-0.0274, P less than 0.01), (CYP7A1: NS 0.3570+/-0.0175 vs EB 0.4802+/-0.0217, P less than 0.01)].

CONCLUSIONEstrogen induces ICP in rats. The mRNA and protein expressions of SHP and CYP7A1 in livers of the ICP rats were increased, which causes more bile acids to be synthesized. This may be one of the mechanisms of ICP.

Animals ; Cholestasis, Intrahepatic ; chemically induced ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; metabolism ; Estradiol ; analogs & derivatives ; pharmacology ; Female ; Liver ; metabolism ; Pregnancy ; Pregnancy Complications ; chemically induced ; metabolism ; Rats ; Receptors, Cytoplasmic and Nuclear ; metabolism