The role of purslane in modulating diverse effects of high fat diet on biochemical, histological, and molecular parameters of rats' liver / O papel da beldroega na modulação de diversos efeitos da dieta rica em gordura nos parâmetros bioquímicos, histológicos e moleculares do fígado de ratos

Abstract Consuming a high-fat diet causes a harmful accumulation of fat in the liver, which may not reverse even after switching to a healthier diet. Different reports dealt with the role of purslane as an extract against high-fat diet; meanwhile, it was necessary to study the potential role of fresh purslane as a hypolipidemic agent. This study is supposed to investigate further the potential mechanism in the hypolipidemic effect of fresh purslane, by measuring cholesterol 7a-hydroxylase (CYP7A1) and low-density lipoprotein receptor (Ldlr). Rats were divided into two main groups: the first one is the normal control group (n=7 rats) and the second group (n=28 rats) received a high fat diet for 28 weeks to induce obesity. Then the high fat diet group was divided into equal four subgroups. As, the positive control group still fed on a high fat diet only. Meanwhile, the other three groups were received high-fat diet supplemented with a different percent of fresh purslane (25, 50 and 75%) respectively. At the end of the experiment, rats were sacrificed and samples were collected for molecular, biochemical, and histological studies. Current study reported that, supplementation of fresh purslane especially at a concentration of 75% play an important role against harmful effects of high-fat diet at both cellular and organ level, by increasing CYP7A1 as well as Ldlr mRNA expression. Also, there were an improvement on the tested liver functions, thyroid hormones, and lipid profile. Fresh purslane plays the potential role as a hypolipidemic agent via modulation of both Ldlr and Cyp7A, which will point to use fresh purslane against harmful effects of obesity.

Resumo O consumo de uma dieta rica em gordura causa um acúmulo prejudicial de gordura no fígado, que pode não reverter mesmo após a mudança para uma dieta mais saudável. Diferentes relatórios trataram do papel da beldroega como um extrato contra uma dieta rica em gordura; entretanto, foi necessário estudar o papel potencial da beldroega fresca como agente hipolipemiante. Este estudo pretende investigar mais profundamente o mecanismo potencial no efeito hipolipidêmico da beldroega fresca, medindo o colesterol 7a-hidroxilase (CYP7A1) e o receptor de lipoproteína de baixa densidade (Ldlr). Os ratos foram divididos em dois grupos principais: o primeiro é o grupo controle normal (n = 7 ratos) e o segundo grupo (n = 28 ratos) recebeu dieta rica em gorduras por 28 semanas para induzir a obesidade. Em seguida, o grupo de dieta rica em gordura foi dividido em quatro subgrupos iguais. Como, o grupo de controle positivo ainda se alimentava apenas com dieta rica em gordura. Enquanto isso, os outros três grupos receberam dieta rica em gordura suplementada com diferentes porcentagens de beldroegas frescas (25%, 50% e 75%), respectivamente. Ao final do experimento, os ratos foram sacrificados e amostras coletadas para estudos moleculares, bioquímica e histológicos. O estudo atual relatou que a suplementação de beldroegas frescas, especialmente a uma concentração de 75%, desempenha papel importante contra os efeitos prejudiciais da dieta rica em gordura em nível celular e orgânico, aumentando a expressão de CYP7A1 e Ldlr mRNA. Além disso, houve melhora nas funções hepáticas testadas, nos hormônios tireoidianos e no perfil lipídico. Beldroegas frescas desempenham papel potencial como agente hipolipemiante por meio da modulação de Ldlr e Cyp7A, o que apontará para o uso de beldroegas frescas contra os efeitos nocivos da obesidade.

Effects of electroacupuncture on CYP7A1 expression in liver of rabbits with atherosclerosis / 中国针灸

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 0.05).@*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.

Hypolipidemic effect of SIPI-7623, a derivative of an extract from oriental wormwood, through farnesoid X receptor antagonism / 中国天然药物

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.

Hypolipidemic effect of SIPI-7623, a derivative of an extract from oriental wormwood, through farnesoid X receptor antagonism / 中国天然药物

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.

Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1

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.

Regulatory effect of coptisine on key genes involved in cholesterol metabolism / 中国中药杂志

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.

Hypocholesterolemic metabolism of dietary red pericarp glutinous rice rich in phenolic compounds in mice fed a high cholesterol diet

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.

Insulin-dependent suppression of cholesterol 7alpha-hydroxlase is a possible link between glucose and cholesterol metabolisms

Cholesterol 7alpha-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and metabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulin-Akt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activities in a dose-dependent manner. Similarly to bile acids, insulin treatment increased small heterodimer partner (SHP) mRNA rapidly and transiently, leading to the suppression of CYP7A1 transcription in both human and rodents. Chromatin immunoprecipitation showed that FOXO1 directly bound to rat CYP1A1 promoter in the absence of insulin. FOXO1 binding to the rat promoter was diminished by insulin treatment as well as by expression of SHP. Our results suggest that the stimulation of insulin- signaling pathway of Akt-FOXO1 and SHP expression may regulate cholesterol/bile acid metabolisms in liver, linking carbohydrate and cholesterol metabolic pathways. A prolonged exposure of insulin in hyperinsulinemic insulin resistance or diabetic status represses CYP7A1 transcription and bile acid biosynthesis through SHP induction and FOXO1 inactivation, leading to impairment of the hepatic cholesterol/bile acid metabolisms.

Insulin-dependent suppression of cholesterol 7alpha-hydroxlase is a possible link between glucose and cholesterol metabolisms

Cholesterol 7alpha-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and metabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulin-Akt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activities in a dose-dependent manner. Similarly to bile acids, insulin treatment increased small heterodimer partner (SHP) mRNA rapidly and transiently, leading to the suppression of CYP7A1 transcription in both human and rodents. Chromatin immunoprecipitation showed that FOXO1 directly bound to rat CYP1A1 promoter in the absence of insulin. FOXO1 binding to the rat promoter was diminished by insulin treatment as well as by expression of SHP. Our results suggest that the stimulation of insulin- signaling pathway of Akt-FOXO1 and SHP expression may regulate cholesterol/bile acid metabolisms in liver, linking carbohydrate and cholesterol metabolic pathways. A prolonged exposure of insulin in hyperinsulinemic insulin resistance or diabetic status represses CYP7A1 transcription and bile acid biosynthesis through SHP induction and FOXO1 inactivation, leading to impairment of the hepatic cholesterol/bile acid metabolisms.

Expression of FXR mRNA, PPAR alpha mRNA and bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the expressions of FXR, PPARa and Bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats.</p><p><b>METHODS</b>60 clean SD pregnant rats were selected and divided randomly into three groups. Since the 13th day of pregnancy rats in control group were injected subcutaneously with refined vegetable oil 2.0 mg/kg/d Rats in no-treated group were injected subcutaneously with the 17-a-ethynylestradiol (EE) 1.25 mg/kg/d until the 17th day. Those rat ih treated group were injected subcutaneously with the 17-a-ethynylestradiol (EE) 1.25 mg/kg/d until the 17th day and then were treated with fenofibrate for another four days until the 21th day. All rats were killed at the 21th day and livers were collected for study. The levels of serum TBA were examined by ELISA. The mRNA expressions of PPARa, FXR, CYP7A1, CYP27A1 and CYP8B1 were examined by real-time PCR. (1)</p><p><b>RESULTS</b>The levels of TBA were significantly higher in no-treated group (68.7+/-4.2)mumol/L and treated group (69.5+/-3.8)mumol/L compared with that of control group (26.6+/-2.3)mumol/L at the 17th day (P value is less than 0.05) and no difference found between treated and no-treated groups (P value is more than 0.05). The levels of TBA were higher in no-treated group (69.4+/-3.7)mumol/L and treated group (48.5+/-4.8)mumol/L as compared to control group (27.1+/-3.2)mumol/L at the 21th day (P value is less than 0.05). The lever of TBA was significantly lower in Treated group compared with No-treated group (P value is less than 0.05). (2) The mRNA expressions of CYP7A1, FXR, CYP27A1 and CYP8B1 increased in No-treated group (1.55+/-0.03, 1.75+/-0.02, 2.45+/-0.01, 2.15+/-0.01, respectively) and were all higher as compared to control group (0.75+/-0.02, 1.25+/-0.03, 0.65+/-0.03, 1.50+/-0.02, respectively) (P value is less than 0.05). However, the mRNA expression of PPARa decreased in No-treated group (0.85+/-0.02) compared with control group (1.45+/-0.02) (P value is less than 0.05). The mRNA expressions of CYP27A1, PPARa and CYP8B1 increased in treated group (1.25+/-0.01, 1.65+/-0.05, 1.65+/-0.02, respectively) and were all higher than that of control group (P value is less than 0.05).</p><p><b>CONCLUSION</b>Abnormal expressions of CYP7A1, FXR, CYP27A1, CYP8B1 and PPARa may play a role in pathogenesis of estrogen-induced intrahepatic cholestasis. Activator of PPARa may be used as therapeutical drug for ICP.</p>

Red yeast rice increases excretion of bile acids in hamsters / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism.</p><p><b>METHODS</b>Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography.</p><p><b>RESULTS</b>Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7alpha-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 3-4 folds compared with the control value.</p><p><b>CONCLUSION</b>Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.</p>

Expressions of SHP and CYP7A1 in pregnant rats with intrahepatic cholestasis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Thirty 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.</p><p><b>RESULTS</b>(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)].</p><p><b>CONCLUSION</b>Estrogen 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.</p>

Hypocholesterolemic effect of stilbene extract from Cajanus cajan L. on serum and hepatic lipid in diet-induced hyperlipidemic mice / 药学学报

Cajanus cajan L. is a natural plant, which contains a lot of potential active components. In the present study, we identified the effects of the stilbene extract from Cajanus cajan L. (sECC) on hepatic cholesterol metabolism in diet-induced (for 4 weeks) hyperlipidemic Kunming mice. All experimental mice were divided into 5 groups: control group, high lipid model group, sECC-treated with 200 or 100 mg kg(-1), and simvastatin (Sim, 12 mg kg(-1)) treated group. The mice were fed with fat and cholesterol-enriched chow except control mice that were fed with standard diet. The effects of sECC were investigated by monitoring serum and liver lipid profile (i. e. cholesterol homeostasis) in mice. To further explore the mechanism of sECC, hepatic cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein (LDL) receptor expressions in cholesterol homeostasis were analyzed by reverse transcription PCR. After 4 weeks pretreatment, the mice in the high lipid model group showed markedly higher serum and hepatic lipid contents than control group (P< 0.01). Compared with high lipid model group, the increased serum and hepatic lipid contents were markedly attenuated by sECC (200 mg kg(-1)), the serum and hepatic total cholesterol were reduced by 31.5% and 22.7% (P<0.05), respectively. The triglyceride contents of serum and liver were also lowered by 23.0% and 14.4%, respectively. At the same times, serum LDL cholesterol decreased by 53.0% (P<0.01). The mRNA expressions of hepatic CYP7A1 and LDL-receptor were significantly enhanced in the mice administered with sECC (200 mg kg(-1)), whereas those expressions were suppressed by the fat and cholesterol-enriched diet. These data indicate that sECC reduces the atherogenic properties of dietary cholesterol in mice. It is indicated that expression enhancement of hepatic LDL-receptor and cholesterol 7alpha-hydroxylase may be responsible for the hypercholesterolemic effect.

Association between cholesterol 7alpha-hydroxylase -204A/C gene polymorphism and endogenous hypertriglyceridemia in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the cholesterol 7alpha-hydroxylase gene -204A/C polymorphism and its relationship with serum lipids and apolipoproteins (apo) levels in patients with endogenous hypertriglyceridemia (HTG) in Chinese population in Chengdu area.</p><p><b>METHODS</b>The genotype and allele frequencies of cholesterol 7alpha-hydroxylase gene -204A/C polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Serum lipids were measured by enzymatic kits and apolipoproteins AI, AII, B100, CII, CIII and E were measured by the RID kits in 132 HTG patients and 212 control subjects.</p><p><b>RESULTS</b>Allele frequencies of A and C were 0.602 and 0.398 in HTG group and 0.601 and 0.399 in control group, respectively. There was no significant difference of allele and genotypes frequencies between HTG and control groups (P> 0.05). In HTG group, carriers with the genotypes CC and AC were associated with significantly higher concentrations of triglycerides and apoCIII compared with those with genotype AA (P< 0.05). In the control group, carriers with the genotypes CC and AC were associated with significantly lower serum high density lipoprotein cholesterol (HDL-C) level compared with those with genotype AA (P< 0.05). In the male control group, carriers with the genotypes CC and AC had elevated levels of serum triglycerides than those with genotype AA (P< 0.05).</p><p><b>CONCLUSION</b>These results suggest that -204A/C polymorphism in the CYP7A1 gene does not relate with HTG but may has an effect on serum triglyceride and apoCIII levels in patients with endogenous HTG, the serum HDL-C level in control subjects and the serum TG level in male control subjects.</p>

Dietary chitosan enhances hepatic CYP7A1 activity and reduces plasma and liver cholesterol concentrations in diet-induced hypercholesterolemia in rats

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.

Relationship between the increase of hepatic D-bifunctional protein activity and bile acid biosynthesis in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Twenty 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.</p><p><b>RESULTS</b>Compared 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).</p><p><b>CONCLUSION</b>The 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.</p>

Linkage of the cholesterol 7alpha-hydroxylase gene and low-density lipoprotein cholesterol conditional on apolipoprotein E association: the National Heart, Lung, and Blood Institute Family Heart Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Genetic 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.</p><p><b>METHODS</b>Our 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>Our 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.</p>