RESUMO
Omega (n)-3 polyunsaturated fatty acids (PUFA) are important regulators of inflammatory response that may impact pregnancy outcome. The effects of breeding chow diets containing n-3 PUFA from either fish oil (FO) or soybean oil (SO) were investigated on tissue fatty acid composition, inflammatory cytokines and pregnancy outcome. Female C57BL/6 mice (7 weeks old) were fed FO or SO diets for 2 weeks before mating and throughout pregnancy. Animals were sacrificed before and during pregnancy at day 6.5, 12.5 and 18.5. The FO diet increased the incorporation of n-3 PUFA in placenta, with a concomitant decrease in the concentration of pro-inflammatory cytokines. The FO diet increased the mRNA expression of placental specific PUFA transporter, which coincided with accretion of n-3 PUFA in fetal brain. Sites of fetal resorption were noticeable in the SO group but not in the FO group. N-3 PUFA may improve fetal sustainability via altering cytokine levels.
Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Inflamação/dietoterapia , Placenta/efeitos dos fármacos , Animais , Citocinas/genética , Citocinas/metabolismo , Feminino , Feto , Óleos de Peixe/administração & dosagem , Inflamação/metabolismo , Camundongos , Placenta/metabolismo , Gravidez , Óleo de Soja/administração & dosagemRESUMO
BACKGROUND: An imbalance of omega (n)-3 and n-6 polyunsaturated fatty acids (PUFA) during critical periods of development may have adverse effects on the health of the newborn in later life. OBJECTIVES: We hypothesized that breastmilk with higher n-6 to n-3 PUFA ratio will have higher inflammatory cytokines and initiate cellular events similar to insulin resistance and obesity. METHODS: Breastmilk was collected from healthy women who gave natural birth at full term. Breastmilk fatty acids were measured using gas chromatography; samples were pooled based on the n-6 to n-3 PUFA ratio (high, medium and low), and soluble cytokines were measured. Pooled samples were used to treat 3T3-L1 cells; mRNA expression of diacylglycerol acyltransferase2, stearoyl-CoA desaturase-1, leptin and RPLPO was measured. RESULTS: Breastmilk with a higher ratio of n-6 to n-3 PUFA showed higher pro-inflammatory cytokines; there was a direct correlation between n-6 PUFA and pro-inflammatory cytokines. Breastmilk with a higher ratio of n-6 to n-3 PUFA increased the expression of genes involved in lipogenesis. CONCLUSIONS: Pro-inflammatory cytokines in breastmilk are associated with higher levels of n-6 PUFA in breastmilk and has the capacity to alter adipose tissue metabolism to likely predispose the newborn to a higher risk of obesity in later life.
Assuntos
Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Resistência à Insulina/fisiologia , Leite Humano/química , Obesidade/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Citocinas/metabolismo , Diacilglicerol O-Aciltransferase/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Feminino , Humanos , Leptina/metabolismo , Lipogênese/fisiologia , Camundongos , Leite Humano/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Ribossômicas/metabolismo , Estearoil-CoA Dessaturase/metabolismoRESUMO
The objective of this experiment was to determine the effect of polyunsaturated fatty acids on gene expression for fatty acid synthase, acetyl CoA-carboxylase, malic enzyme, pyruvate kinase, and phosphoenolpyruvate carboxykinase in obese mice. Eight-week-old female lean and obese mice were fed semi-purified diets containing 20% (w/w) fat of either high or low polyunsaturated to saturated (P/S) fatty acid ratio for four weeks. Total RNA was isolated from liver and was hybridized to cDNA probes for the above enzymes. Consumption of a high P/S diet decreased mRNA levels for all the lipogenic enzymes studied in both lean and obese mice. Compared to lean mice, obese mice exhibited a higher mRNA level for fatty acid synthase, acetyl CoA-carboxylase, malic enzyme, and pyruvate kinase in animals fed either a high or low P/S diet. Enzyme-specific activities followed the same profile as the mRNA levels in both lean and obese mice fed a high or low P/S diet. The decrease in liver fatty acid synthase mRNA level was more pronounced in lean mice compared to obese mice, suggesting that the obese mice may be more resistant to polyunsaturated fatty acid feedback control of gene expression.
Assuntos
Metabolismo dos Carboidratos , Gorduras na Dieta/farmacologia , Regulação Enzimológica da Expressão Gênica , Lipídeos/biossíntese , Obesidade/metabolismo , Acetil-CoA Carboxilase/genética , Animais , Peso Corporal , Dieta , Ácidos Graxos Insaturados/metabolismo , Feminino , Fígado/enzimologia , Malato Desidrogenase/genética , Camundongos , Camundongos Obesos , Obesidade/genética , Tamanho do Órgão , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Piruvato Quinase/genética , RNA Mensageiro/análiseRESUMO
Insulin binding to the plasma membrane is known to be altered by modifying the membrane composition through dietary treatment. As insulin binding receptors are also present on nuclear membrane, this study was undertaken to investigate if specific binding of insulin to the liver nuclei is altered by diet. 8-wk-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low polyunsaturated-to-saturated (P/S) fatty acid ratio for 4 wk. Liver nuclei were prepared, insulin binding was measured and nuclear phospholipids were isolated for lipid analysis. Insulin binding was highest in nuclei prepared from lean mice fed a high P/S diet. Specific binding of insulin to nuclei prepared from obese mice was also increased by the high P/S diet, but to a lesser extent compared to lean mice. Feeding a high P/S diet increased polyunsaturated fatty acid content of membrane phospholipids from both lean and ob/ob mice. Obese mice were characterized by higher levels of arachidonic acid and lower levels of linoleic acid in phosphatidylcholine. The present study establishes that insulin binding to liver nuclei is increased by feeding a high P/S diet, and that insulin binding to liver nuclei from obese mice is lower than from lean mice.
Assuntos
Gorduras na Dieta/farmacologia , Insulina/metabolismo , Fígado/metabolismo , Membrana Nuclear/metabolismo , Animais , Peso Corporal , Ácidos Graxos/análise , Feminino , Fígado/efeitos dos fármacos , Camundongos , Camundongos Obesos , Membrana Nuclear/efeitos dos fármacos , Tamanho do Órgão , Fosfolipídeos/metabolismo , Receptor de Insulina/efeitos dos fármacosRESUMO
Atherosclerosis is a major cause of death for mankind. Although the pathophysiology of atherosclerosis is a complex and multifactorial process, growing body of evidence has identified phospholipids-mediated signaling as an important factor in the induction and progression of atherosclerosis. Lysophosphatidylcholine (LPC) is a major phospholipid in oxidized low-density lipoprotein, and is generally considered to be atherogenic. However, some studies have shown anti-atherogenic properties of LPC. The controversial findings surrounding the pro- or anti-atherogenic properties of LPC appear to be due to the chain length and the degree of saturation of the fatty acyl moiety of LPC. Studies have suggested that the presence of omega (n)-polyunsaturated fatty acids (PUFA) at the sn-1 position of LPC modulates the inflammatory response thereby making LPC anti-atherogenic. We have recently shown that feeding a diet high in n-3 PUFA resulted in the enrichment of LPC in both plasma and liver of C57BL/6 mice with n-3 PUFA. Others have also shown that supplementation with fish oil leads to preferential incorporation of n-3 PUFA into LPC. We also found that plasma obtained from mice fed a diet high in n-3 PUFA showed higher cholesterol efflux capacity compared to animals fed a low n-3 PUFA diet, despite no changes in high-density lipoprotein concentrations. We are therefore hypothesizing that n-3 PUFA enriched LPC has anti-atherogenic properties by promoting cholesterol efflux from macrophages and by reducing inflammation. Our anticipated long term objective is to establish that the fatty acyl moiety of LPC can be used as a potential biomarker for the risk of developing atherosclerosis. Validating this hypothesis would have a substantial impact on the public health with respect to early diagnosis of cardiovascular risks, and designing dietary based therapeutic strategies for the prevention and management of atherosclerosis and other heart related diseases.
Assuntos
Aterosclerose/metabolismo , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Lisofosfatidilcolinas/química , Lisofosfatidilcolinas/metabolismo , Modelos Cardiovasculares , Acilação , Animais , Biomarcadores/química , Biomarcadores/metabolismo , Medicina Baseada em Evidências , Humanos , Camundongos Endogâmicos C57BLRESUMO
This study was designed to determine the level of inhibition of gene transcription by the reduction in insulin levels upon the onset of diabetes in spontaneously diabetic B/B rats and if reducing the level of polyunsaturated fatty acids (PUFA) in the diet will increase lipogenic enzyme activity. Control (eight animals per group) and spontaneously diabetic B/B male weanling rats (25 animals per group) were fed semipurified diets containing 20% (w/w) fat of either low (0.25) or high (1.0) polyunsaturated to saturated (P/S) fatty acid ratio. Rats were killed at the onset of diabetes [blood glucose level of approximately/= 100 mg/dL (5.55 mM)] and as they became highly diabetic [blood glucose level of approximately/= 400 mg/dL (22.22 mM)]. Total RNA was extracted from liver, and the relative amount of mRNA coding for fatty acid synthase (FAS), acetyl-CoA carboxylase, malic enzyme, pyruvate kinase, and phosphoenolpyruvate carboxykinase was determined. Liver enzyme activities were also measured. The mRNA levels for FAS, acetyl-CoA carboxylase, and malic enzyme decreased compared to control animals. The mRNA level for pyruvate kinase decreased at the onset of diabetes as compared to control animals. Feeding animals the low P/S diet treatment elevated the level of mRNA and lipogenic enzyme activity compared to animals fed the high P/S diet treatment, suggesting that the effect of PUFA on lipogenic enzymes is through a direct effect on gene expression.
Assuntos
Diabetes Mellitus Tipo 1/enzimologia , Gorduras na Dieta/farmacologia , Lipídeos/biossíntese , Acetil-CoA Carboxilase/genética , Animais , Glicemia/metabolismo , Ácido Graxo Sintases/genética , Insulina/sangue , Fígado/enzimologia , Malato Desidrogenase/genética , Masculino , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Piruvato Quinase/genética , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos BB , Receptor fas/genéticaRESUMO
There is clear evidence of the effects of sex and age on the prevalence of cardiovascular disease. We investigated the interactions of dietary omega (n)-3 polyunsaturated fatty acids (PUFA), sex, and age on plasma lipids and lipoproteins in the offspring of C57BL/6 mice exposed to high, medium, or low n-3 PUFA at weaning and 16 weeks postweaning. There was an increase in plasma triglycerides from weaning to 16 weeks in male and female offspring; however, the high n-3 PUFA group showed a reduction in triglycerides in both sexes at 16 weeks. High n-3 PUFA caused an increase in plasma LDL-cholesterol from weaning to 16 weeks in male offspring; however, the LDL particle size was significantly larger in the high n-3 PUFA group. Plasma from male mice showed higher cholesterol efflux compared to females; high n-3 PUFA increased cholesterol efflux. Thus the effects of n-3 PUFA are age and sex dependent.
Assuntos
LDL-Colesterol/sangue , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Lipoproteínas/sangue , Triglicerídeos/sangue , Fatores Etários , Animais , Animais Recém-Nascidos , Transporte Biológico , Feminino , Alimentos Formulados , Masculino , Camundongos Endogâmicos C57BL , Fatores Sexuais , DesmameRESUMO
Insulin binding to the nucleus in vivo alters the binding of transcription factors to the promoter region of lipogenic genes, thereby changing expression of these genes. The present research was designed to investigate whether change in diet fat composition alters insulin binding to nuclear insulin receptors at various stages of onset of diabetes in spontaneously diabetic B/B rats. The fatty acid composition of lipids comprising the nuclear membrane was also examined. Weanling rats were fed a nonpurified diet (low-fat commercial rat chow) or a semipurified diet containing 20 g/100 g fat of either high (1.0) or low (0.25) polyunsaturated to saturated (P/S) fatty acid ratio. Insulin binding to liver nuclei was measured when the blood glucose level was 100 mg/dl and 400 mg/dl. No effect of diet treatment on age of onset of diabetes was found. Specific binding of insulin to nuclei from rats with a blood glucose level of 100 mg/dl did not differ from nondiabetic rats, and was higher than in diabetic rats with a blood glucose level of 400 mg/dl. Insulin binding was greater in rats fed a high P/S diet. The high versus low P/S diet treatment primarily altered the fatty acid composition of phosphatidylinositol in the nuclear membrane. Diabetic rats fed nonpurified diet showed a significant increase in levels of 18:2(n-6) and 22:6(n-3), whereas 20:4(n-6) decreased in the phosphatidylcholine fraction compared with control rats fed chow. As rats became diabetic, the level of monounsaturated fatty acids, 18:2(n-6) and 22:6(n-3) decreased, whereas the level of 20:4(n-6) increased in phosphatidylinositol. Change in the composition of these nuclear membrane components may be associated with transitions in insulin binding.
RESUMO
We examined whether the degree of saturation of C-18 fatty acids influenced hepatic cholesterol metabolism in C3H mice. The mice were fed diets containing 20 g/100 g fat, enriched in stearic (18:0), oleic (18:1) or linoleic acid (18:2) with or without 1 g/100 g cholesterol. Plasma total cholesterol concentration was lower in mice fed the 18:0 diet relative to those fed the 18:1- or 18:2-enriched diets (P < 0.05) regardless of dietary cholesterol supplementation. Dietary cholesterol significantly raised hepatic total cholesterol concentration (P < 0.05) in those fed the 18:1- and 18:2-enriched diets, but not in mice fed the 18:0-enriched diet. Dietary cholesterol raised biliary cholesterol concentration (P < 0. 05) in mice fed the 18:1- and 18:2-enriched diets, but not in mice fed the 18:0-enriched diet. The cholesterol saturation index was variably affected by the fat diets. Feeding diets containing cholesterol suppressed the hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity and induced acyl coenzyme A:cholesterol acyl transferase (ACAT) activity compared with feeding diets without cholesterol (P < 0.05), indicating that the liver was exposed to dietary cholesterol. Hepatic ACAT activity was lower in mice fed the 18:0-enriched diet compared with those fed the 18:1- or 18:2-enriched diets (P < 0.05). Addition of cholesterol to the 18:1 diet induced the largest increase of hepatic ACAT activity, and this was associated with the enrichment of VLDL with cholesterol. Varying the degree of saturation of C-18 fatty acids influences the metabolism and disposition of hepatic cholesterol.
Assuntos
Colesterol/metabolismo , Gorduras na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos/farmacologia , Fígado/metabolismo , Animais , Bile/química , Bile/metabolismo , Colesterol/sangue , Colesterol 7-alfa-Hidroxilase/metabolismo , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos/análise , Ácidos Graxos Insaturados/análise , Feminino , Hidroximetilglutaril-CoA Redutases/metabolismo , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos C3H , Microssomos Hepáticos/metabolismo , Esterol O-Aciltransferase/metabolismoRESUMO
To investigate the importance of the 3'-untranslated region (UTR) of the mouse cholesterol 7alpha-hydroxylase (cyp7) mRNA in post-transcriptional regulation of expression of the cyp7 gene, chimaeric genes encoding mRNA containing the structural sequence of chloramphenicol acetyltransferase (CAT) linked to either the 3'-UTR of the mouse cyp7 mRNA or the SV40 early gene mRNA were constructed. The human cytomegalovirus (CMV) promoter was used to drive the expression of all the chimaeric genes. Thus the transgenes had identical sequences in the promoter, the regions encoding the 5'-UTR and translated sequence but differed in the region encoding the 3'-UTR of their respective mRNA species. The transgene containing the entire cyp7 3'-UTR (designated CMV.CAT.CYP7) gave rise to CAT activity in transfected hepatoma cells that was one-quarter of that obtained in cells transfected with the transgene containing the SV40 3'-UTR (designated CMV.CAT.SV40). The 3'-UTR of the cyp7 mRNA contains sequences resembling AU-rich elements (AREs). Deleting eight of nine putative AREs from the CYP7 3'-UTR sequence increased the CAT activity to a level greater than that observed for CMV.CAT. SV40, whereas deletion of the intron region had no effect. These results show that the AREs of the 3'-UTR of the cyp7 mRNA decrease transgene expression. Bile acids are known to repress the expression of the cyp7 gene. To test whether the 3'-UTR of the cyp7 mRNA has a role in this process, the expression of the chimaeric genes was evaluated in hepatoma cells competent for bile acid uptake. Conjugated bile acids, but not unconjugated bile acids, further decreased the expression of the CMV.CAT.CYP7 transgene. The same bile acids had no effect on the expression of the CMV.CAT.SV40 transgene. Deletion of the intron from the cyp7 sequence did not alter the CAT activity compared with the parental plasmid, and also did not alter the sensitivity of the transgene to the conjugated bile acids. Deletion of the AREs from the cyp7 3'-UTR, which increased the expression of the transgene, did not abolish the sensitivity of the transgene to repression by conjugated bile acids. Thus the 3'-UTR of the mouse cyp7 mRNA also contains elements that facilitate the further repression of transgene expression in the presence of conjugated bile acids. The results indicate that the 3'-UTR of the mouse cyp7 mRNA contains information specifying regulation at the post-transcriptional level.
Assuntos
Ácidos e Sais Biliares/farmacologia , Colesterol 7-alfa-Hidroxilase/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , RNA Mensageiro/genética , Animais , Sequência de Bases , Clonagem Molecular , Repressão Enzimática , Éxons , Genes Reporter , Camundongos , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão , Sequências Reguladoras de Ácido Nucleico , Ácido Tauroquenodesoxicólico/farmacologia , TransgenesRESUMO
We determined if fatty acids can regulate the murine Cyp7a1 and human CYP7A1 gene promoters via peroxisome proliferator-activated receptor alpha (PPARalpha)/9-cis-retinoic acid receptor alpha (RXRalpha). In transfected cells, the murine Cyp7a1 gene promoter displayed markedly lower basal activity, but greater sensitivity to fatty acid- or WY 14,643-activated PPARalpha/RXRalpha when compared with the human CYP7A1 gene promoter. PPARalpha/RXRalpha can bind to a site (Site II) located within the region at nucleotides -158 to -132 of both promoters. Mutagenesis of the human CYP7A1 Site II element abolished the response to activated PPARalpha/RXRalpha. The murine Cyp7a1 gene promoter contains an additional PPARalpha/RXRalpha-binding site (Site I) located within nucleotides -72 to -57. Replacement of a single residue in human CYP7A1 Site I with that found in the murine Cyp7a1 Site I sequence enabled PPARalpha/RXRalpha binding, and this mutation resulted in reduced basal activity, but substantially improved the response to activated PPARalpha/RXRalpha in transfected cells. We conclude that fatty acids can regulate the cyp7a gene promoter via PPARalpha/RXRalpha. The differential response of the murine Cyp7a1 and human CYP7A1 gene promoters to PPARalpha activators is attributable to the additional PPARalpha/RXRalpha-binding site in the murine Cyp7a1 gene promoter.
Assuntos
Colesterol 7-alfa-Hidroxilase/genética , Ácidos Graxos/metabolismo , Regulação Enzimológica da Expressão Gênica , Regiões Promotoras Genéticas , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores do Ácido Retinoico/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Clonagem Molecular , Humanos , Camundongos , Mutagênese Sítio-Dirigida , Ratos , Proteínas Recombinantes/metabolismo , Receptor alfa de Ácido Retinoico , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Transfecção , Células Tumorais CultivadasRESUMO
Cholesterol 7 alpha-hydroxylase (cyp7) is the rate-limiting enzyme in bile acid biosynthesis. Previously, dietary cholesterol was shown to induce cyp7 gene expression. However, recent studies have produced data that are inconsistent with this observation, suggesting the possibility that other factors in the diet are also important in the regulation of cyp7 by dietary cholesterol. The effect of dietary fats on the ability of dietary cholesterol to regulate cyp7 activity and mRNA abundance was assessed. High fat diets composed primarily of polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) fatty acids induced hypercholesterolemia regardless of whether cholesterol was present or not. However, the effects of each diet on bile composition and hepatic cholesterol content were variable. Microsomal fatty acid profiles reflected the fatty acid composition of the diets. Addition of cholesterol to the PUFA diet increased cyp7 mRNA abundance and activity, analogous with the results observed in mice fed a chow plus cholesterol diet. On the other hand, addition of cholesterol to diets high in MUFA or SFA caused a significant reduction of cyp7 mRNA abundance and activity. Addition of cholesterol to all the diets caused the expected changes in low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA abundance but was not correlated with the changes in cyp7 mRNA abundance. The relationship between cyp7 mRNA abundance and hepatic total cholesterol content or hepatic microsomal cholesterol content was evident, suggesting that cholesterol status does not necessarily determine cyp7 mRNA abundance. The results of this study illustrate that the type of dietary fat is important in elaborating the regulatory potential of dietary cholesterol on cyp7 gene expression and suggest that the regulation of cyp7 gene expression does not involve the classical sterol-mediated pathway.
Assuntos
Colesterol 7-alfa-Hidroxilase/genética , Colesterol na Dieta/farmacologia , Gorduras na Dieta/efeitos adversos , Regulação Enzimológica da Expressão Gênica/genética , Hipercolesterolemia/etiologia , Animais , Bile/química , Ácidos e Sais Biliares/química , Colesterol/análise , Colesterol/sangue , Colesterol 7-alfa-Hidroxilase/metabolismo , Colesterol na Dieta/administração & dosagem , Estudos de Coortes , Gorduras na Dieta/análise , Gorduras na Dieta/metabolismo , Ingestão de Alimentos/fisiologia , Ácidos Graxos/análise , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/classificação , Ácidos Graxos Insaturados/metabolismo , Feminino , Expressão Gênica/genética , Hidroximetilglutaril-CoA Redutases/genética , Lipídeos/química , Fígado/química , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/química , RNA Mensageiro/análise , RNA Mensageiro/genética , Receptores de LDL/genética , Aumento de Peso/fisiologiaRESUMO
Intestinal and hepatic recovery of bile acids is principally mediated by sodium dependent bile acid transporters. Of these, the ileal sodium bile acid transporter (isbt) and the hepatic sodium bile acid cotransporting polypeptide (ntcp) may be most important in determining the efficiency of bile acid recovery within the enterohepatic circulation. We used molecular probes to explore the relationship between the bile acid recovery pathway, at the level of isbt and ntcp, and the biosynthetic pathway, at the level of cholesterol 7 alpha-hydroxylase (cyp7). Taurocholate feeding of mice suppressed ntcp, isbt, and cyp7 mRNA levels as compared to controls. Cholestyramine feeding induced both cyp7 and isbt mRNA gene expression. Cholesterol feeding induced cyp7 mRNA levels but suppressed isbt gene expression. These results suggest that in mice the bile acid recovery and biosynthetic pathways are coordinately regulated, and these pathways may be responsive to the size of the bile acid pool in the enterohepatic circulation.
Assuntos
Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo , Colesterol na Dieta/farmacologia , Mucosa Intestinal/metabolismo , Transportadores de Ânions Orgânicos Dependentes de Sódio , Simportadores , Transcrição Gênica , Animais , Anticolesterolemiantes/farmacologia , Ácidos e Sais Biliares/biossíntese , Proteínas de Transporte/biossíntese , Colesterol 7-alfa-Hidroxilase/biossíntese , Resina de Colestiramina/farmacologia , Feminino , Regulação da Expressão Gênica , Homeostase , Íleo/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/biossíntese , Suínos , Ácido Taurocólico/farmacologia , Transcrição Gênica/efeitos dos fármacosRESUMO
Both experimental and clinical studies have indicated that a novel source of dietary fibre, produced from rhubarb (Rheum rhaponticum) stalks, is potentially hypolipidaemic. The present study, using C57BL/6J mice, was undertaken to examine if this fibre source affects cholesterol degradation. Mice were maintained on semi-purified diets containing 50 g rhubarb fibre or cellulose/kg with or without 5 g cholesterol/kg for 4 weeks. In cholesterol-supplemented mice, rhubarb fibre caused significant lowering of plasma cholesterol (-13%) and the hepatic concentrations of total cholesterol (-34%) and cholesteryl esters (-34%). In parallel to the reduction of hepatic cholesteryl ester content, animals fed on rhubarb fibre had significantly lower activity of acyl CoA: cholesterol acyltransferase (EC 2.3.1.26) than the mice maintained on a diet containing cellulose and cholesterol. Rhubarb-fibre feeding accelerated the faecal bile-acid loss and diminished the gall-bladder bile-acid pool in both the normal and the cholesterol-fed mice. The increase in the bile-acid excretion was positively correlated with an increased activity as well as mRNA abundance of cholesterol 7 alpha-hydroxylase (EC 1.14.13.17). The increased excretion of bile acids and induction of cholesterol 7 alpha-hydroxylase activity may account for the hypocholesterolaemic effect of rhubarb fibre.