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1.
Nutrients ; 11(2)2019 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-30717491

RESUMO

Carob fruit extract (CFE) has shown remarkable in vitro antioxidant properties and reduces postprandial hyperglycemia and hyperlipidemia in healthy animals. Development of functional meat products that contain bioactive components are presented as a great nutritional strategy. Until now, the effect of the consumption of restructured meat enriched with CFE in a murine model of diabetes has not been investigated. The objective of this study was to evaluate the effect on glycemia, lipemia, lipoprotein profile, Ldlr, arylesterase (AE), and very low-density lipoproteins (VLDL) and liver oxidation in streptozotocin-nicotinamide (STZ-NAD) growing Wistar diabetic rats fed restructured meat in the frame of a high cholesterol/high saturated-fat diet. In the present study, three groups (D, ED and DE) were fed cholesterol-enriched (1.4% cholesterol and 0.2% cholic acid) and high saturated-fat diets (50% of total energy from fats and 20.4% from saturated fatty acids). Rats were subjected to a STZ-NAD administration at the 3rd week. Group D did not receive CFE, while ED and DE rat groups received CFE before and after the diabetic induction, respectively. After eight weeks, D rats showed hyperglycemia and hypercholesterolemia, an increased amount cholesterol-enriched VLDL (ß-VLDL), IDL and LDL particles and triglyceride-enriched HDL. ED and DE partially blocked the hypercholesterolemic induction with respect to D group (p < 0.001) and improved glycemia, cholesterol levels, lipoprotein profile, Ldlr, plasma AE activity and liver oxidation (p < 0.001). Fecal fat, moisture and excretion were higher while dietary digestibility was lower in ED and DE vs. D counterparts (p < 0.001). In conclusion, CFE-enriched meat shows, for the first time, hypoglycemic and hypolipidemic effects in STZ-NAD animals fed high cholesterol/high saturated-fat diets. Likewise, it manages to reverse possible diabetes lipoprotein alterations if CFE-enriched meat is consumed before pathology development or improves said modifications if Type 2 Diabetes Mellitus is already established.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Dieta Aterogênica/efeitos adversos , Fabaceae , Lipoproteínas VLDL/sangue , Carne , Extratos Vegetais/uso terapêutico , Receptores de LDL/sangue , Animais , Glicemia/metabolismo , Hidrolases de Éster Carboxílico/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gorduras na Dieta/efeitos adversos , Digestão , Fezes , Manipulação de Alimentos , Frutas , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Lipoproteínas/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos Wistar , Triglicerídeos/sangue
2.
Nutrients ; 10(12)2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30486328

RESUMO

Restructuring pork (RP) by adding new functional ingredients, like Chia oil (one of the richest natural source of α-linolenic acid) or hydroxytyrosol (HxT) (potent antioxidant), both with hypolipidemic activities, is one of the strategies that may help to reduce the potential negative effects of high meat products consumption. The aim of this study was to evaluate the Chia oil- or HxT-enriched-RP effect on the lipoprotein profile of aged rats fed high-fat, high-energy, and cholesterol-enriched diets. RP samples were prepared by mixing lean pork and lard with or without Chia oil (152.2 g/kg fresh matter) or HxT (3.6 g/kg fresh matter). Diets were prepared by mixing a semisynthetic diet with freeze-dried RP. Groups of 1-year male Wistar rats were fed the following experimental diets for 8 weeks: C, control-RP diet; HC, cholesterol-enriched-RP diet; and Chia oil-RP (CHIA) and HxT, Chia oil- or hydroxytyrosol-RP, cholesterol-enriched diet. Plasma lipid, lipoprotein profile, SREBP-1c protein, and low-density lipoproteins (LDL) receptor gene (Ldlr) expressions were evaluated. Compared to C diet, the HC diet increased plasma cholesterol, triglycerides, free fatty acids, total lipids, and SREBP-1c expression, but reduced Ldlr expression and significantly modified the lipoprotein profile, giving rise to the presence of high levels of atherogenic cholesterol-enriched very low-density lipoproteins (VLDL) particles. Compared to the HC diet, the HxT diet did not produce significant changes in feed intake but it reduced the body weight. Chia oil and HxT partially arrested the negative effects of the high-fat, high-energy, and cholesterol-enriched meat-based diets on lipemia and lipoproteinemia, mostly by reducing the amount of cholesterol content in VLDL (60% and 74% less in CHIA and HxT vs. HC, respectively) and the VLDL total mass (59% and 63% less in CHIA and HxT vs. HC, respectively). Free fatty acids (FFA) significantly correlated with adipose tissue weight and VLDL total mass (both p < 0.05), and plasma triglycerides, phospholipids, total lipids, and SREBP-1c (all p < 0.001), suggesting the important role of FFA in lipoprotein metabolism. Results support the recommendation to include these ingredients in pork products addressed to reduce the presence of increased atherogenic particles in aged people at CVD risk consuming large amounts of pork.


Assuntos
Colesterol na Dieta/sangue , Dieta Hiperlipídica , Lipoproteínas LDL/sangue , Álcool Feniletílico/análogos & derivados , Óleos de Plantas/farmacologia , Carne Vermelha , Salvia/química , Tecido Adiposo , Animais , Antioxidantes/farmacologia , Colesterol na Dieta/administração & dosagem , Ácidos Graxos/sangue , Lipoproteínas VLDL/sangue , Masculino , Álcool Feniletílico/farmacologia , Fosfolipídeos/sangue , Óleos de Plantas/metabolismo , Ratos Wistar , Receptores de LDL/sangue , Sementes , Proteína de Ligação a Elemento Regulador de Esterol 1/sangue , Suínos , Triglicerídeos/sangue , Ácido alfa-Linolênico/sangue , Ácido alfa-Linolênico/farmacologia
3.
BMC Complement Altern Med ; 17(1): 222, 2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28427397

RESUMO

BACKGROUND: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects. METHODS: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR-/-) mice fed a high-cholesterol diet for 13 weeks. Mice were randomized in to 6 groups: ND (normal diet) group, HCD (high-cholesterol diet) group, and treatment groups fed HCD and treated with simvastatin (10 mg/kg, p.o.) or HVC1 (10, 50, or 250 mg/kg, p.o.). RESULTS: HVC1 regulated the levels of total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol in mouse serum. In addition, it regulated the transcription level of the peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding proteins (SREBP)-2, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, lipoprotein lipase (LPL), apolipoprotein B (apo B), liver X receptor (LXR), and inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Furthermore, HVC1 activated 5' adenosine monophosphate-activated protein kinase (AMPK). CONCLUSION: Our results suggest that HVC1 might be effective in preventing high-cholesterol diet-induced hyperlipidemia by regulating the genes involved in cholesterol and lipid metabolism, and inflammatory responses.


Assuntos
Anti-Inflamatórios/farmacologia , Colesterol/sangue , Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias , Hipolipemiantes/farmacologia , Inflamação , Fitoterapia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Apolipoproteínas B/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Citocinas/metabolismo , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/etiologia , Hipolipemiantes/uso terapêutico , Inflamação/sangue , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Knockout , Receptores de LDL/sangue , Receptores de LDL/deficiência , Receptores de LDL/genética , Fatores de Transcrição/metabolismo , Triglicerídeos/sangue
4.
Nutr Res ; 37: 87-96, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28215318

RESUMO

Accumulating evidence has suggested that intake of whole grains is a protective factor against pathogenesis of coronary artery disease. The exact mechanisms, however, are still not clearly understood. In this study, we hypothesized that adequate intake of corn fractions (aleurone, endosperm and germ) can modify lipid profiles in relation to atherosclerotic lesion development in low-density lipoprotein receptor knockout (LDLr-KO) mice. The purpose of the present study was to investigate the potential cardiovascular benefits of corn fractions in LDLr-KO mice through a number of biomarkers including lipid profile, and morphologic and morphometrical analysis of atherosclerotic lesions in aortic root. Four groups of male LDLr-KO mice were fed with the experimental diets supplemented with (3 treated) or without (control) 5% (wt/wt) of each of corn fractions for 10 weeks. All diets were supplemented with 0.06% (wt/wt) cholesterol. Compared with mice in the control group, atherosclerotic lesions in the aortic roots were significantly reduced (P=.003) in the mice that were fed diet supplemented with aleurone and germ fractions. This effect was associated with significant reductions in plasma total (P=.02) and LDL (P=.03) cholesterol levels, and an increase in fecal cholesterol excretion (P=.04). Furthermore, abdominal fat mass was significantly reduced by consumption of aleurone (P=.03). In summary, the consumption of aleurone and germ may help attenuate atherosclerosis by reducing plasma total and LDL cholesterol levels.


Assuntos
Aterosclerose/dietoterapia , Dieta , Grão Comestível , Lipoproteínas LDL/sangue , Preparações de Plantas/uso terapêutico , Receptores de LDL/sangue , Zea mays , Gordura Abdominal/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Biomarcadores/sangue , Colesterol na Dieta , Fibras na Dieta , Suplementos Nutricionais , Endosperma , Fezes/química , Masculino , Camundongos , Camundongos Knockout , Preparações de Plantas/farmacologia , Proteínas de Plantas , Estruturas Vegetais , Placa Aterosclerótica/prevenção & controle
5.
Horm Metab Res ; 49(6): 446-451, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28235206

RESUMO

Limited data are available evaluating the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid-signaling pathway in women with polycystic ovary syndrome (PCOS). This study was conducted to evaluate the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid signaling pathway in women with PCOS. This randomized double blind, placebo-controlled trial was done among 60 women aged 18-40 years old and diagnosed with PCOS according to the Rotterdam criteria. Participants were randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid (n=30) or placebo (n=30) twice a day for 12 weeks. Gene expressions involved in the insulin and lipid-signaling pathway were quantified in blood samples of PCOS women with RT-PCR method. Quantitative results of RT-PCR demonstrated that compared with the placebo, omega-3 fatty acids supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) mRNA (p=0.005) in peripheral blood mononuclear cells of women with PCOS. In addition, compared to the placebo, omega-3 fatty acids supplementation downregulated expressed levels of oxidized low-density lipoprotein receptor (LDLR) mRNA (p=0.002) in peripheral blood mononuclear cells of women with PCOS. We did not observe any significant effect of omega-3 fatty acids supplementation on expressed levels of glucose transporter 1 (GLUT-1) and lipoprotein(a) [Lp(a)] genes in peripheral blood mononuclear cells. Overall, omega-3 fatty acids supplementation for 12 weeks in PCOS women significantly improved gene expression of PPAR-γ and LDLR.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/metabolismo , Lipídeos/química , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , Transdução de Sinais , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Placebos , Síndrome do Ovário Policístico/sangue , Receptores de LDL/sangue
6.
Mol Nutr Food Res ; 60(9): 2008-19, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27004411

RESUMO

SCOPE: Isoflavones are discussed to improve serum lipoproteins and body composition and to reduce cardiovascular disease risk in postmenopausal women (PMW). LDL receptors (LDLR) and scavenger receptor CD36 (CD36) play a pivotal role in the regulation of plasma LDL-cholesterol concentrations (LDL-chol). We investigated the impact of isoflavones on the receptor expression of both receptors in leukocytes of PMW. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled trial in parallel design was conducted to assess the effects of an isoflavone-enriched soy extract (117.4 mg/day isoflavone aglycone equivalents) for 12 weeks on serum LDL-chol, LDLR, and CD36 expression on leukocytes in 170 healthy PMW. Baseline and after 12 weeks, blood lipid concentrations, anthropometric data and body composition were determined. Receptor expression on leukocytes was measured by means of flow cytometry. After the intervention, no significant differences were found for LDLR and CD36 expression on leukocytes. A significant increase of serum LDL-chol was shown for the isoflavone group (p = 0.03) after 12 weeks. Body fat content and VAT were not affected. CONCLUSION: Isoflavone supplementation for 12 weeks did not change LDLR and CD36 expression on leukocytes of PMW and did not affect body fat content and visceral adipose tissue (VAT), but slightly increased serum LDL-chol.


Assuntos
Antígenos CD36/sangue , Isoflavonas/farmacologia , Pós-Menopausa , Receptores de LDL/sangue , Idoso , Composição Corporal/efeitos dos fármacos , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Lipídeos/sangue , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Pós-Menopausa/efeitos dos fármacos , Glycine max/química
7.
J Nutr ; 144(3): 252-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24368431

RESUMO

Dietary choline is required for proper structure and dynamics of cell membranes, lipoprotein synthesis, and methyl-group metabolism. In mammals, choline is synthesized via phosphatidylethanolamine N-methyltransferase (Pemt), which converts phosphatidylethanolamine to phosphatidylcholine. Pemt(-/-) mice have impaired VLDL secretion and developed fatty liver when fed a high-fat (HF) diet. Because of the reduction in plasma lipids, Pemt(-/-)/low-density lipoprotein receptor knockout (Ldlr(-/-)) mice are protected from atherosclerosis. The goal of this study was to investigate the importance of dietary choline in the metabolic phenotype of Pemt(-/-)/Ldlr(-/-) male mice. At 10-12 wk of age, Pemt(+/+)/Ldlr(-/-) (HF(+/+)) and half of the Pemt(-/-)/Ldlr(-/-) (HF(-/-)) mice were fed an HF diet with normal (1.3 g/kg) choline. The remaining Pemt(-/-)/Ldlr(-/-) mice were fed an HF diet supplemented (5 g/kg) with choline (HFCS(-/-) mice). The HF diet contained 60% of calories from fat and 1% cholesterol, and the mice were fed for 16 d. HF(-/-) mice lost weight and developed hepatomegaly, steatohepatitis, and liver damage. Hepatic concentrations of free cholesterol, cholesterol-esters, and triglyceride (TG) were elevated by 30%, 1.1-fold and 3.1-fold, respectively, in HF(-/-) compared with HF(+/+) mice. Choline supplementation normalized hepatic cholesterol, but not TG, and dramatically improved liver function. The expression of genes involved in cholesterol transport and esterification increased by 50% to 5.6-fold in HF(-/-) mice when compared with HF(+/+) mice. Markers of macrophages, oxidative stress, and fibrosis were elevated in the HF(-/-) mice. Choline supplementation normalized the expression of these genes. In conclusion, HF(-/-) mice develop liver failure associated with altered cholesterol metabolism when fed an HF/normal choline diet. Choline supplementation normalized cholesterol metabolism, which was sufficient to prevent nonalcoholic steatohepatitis development and improve liver function. Our data suggest that choline can promote liver health by maintaining cholesterol homeostasis.


Assuntos
Colesterol/metabolismo , Colina/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Animais , Ésteres do Colesterol/metabolismo , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/etiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica , Fosfatidiletanolamina N-Metiltransferase/sangue , Receptores de LDL/sangue , Triglicerídeos/metabolismo
8.
Plant Foods Hum Nutr ; 68(4): 396-402, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24122546

RESUMO

Hyperlipidemia and hepatic steatosis are frequent alterations due to alcohol abuse. Amaranth is a pseudocereal with hypolipidemic potential among other nutraceutical actions. Here we study the effect of Amaranthus hypochondriacus (Ah) seeds on serum and liver lipids, and the expression of genes associated to lipid metabolism and liver histology in male Wistar rats intoxicated with ethanol. The animals were divided into four groups; two groups were fed the American Institute of Nutrition 1993 for maintenance diet (AIN-93M), and the other two with AIN-93M containing Ah as protein source. One of each protein group received 20% ethanol in the drinking water, thus obtaining: CC (control casein), EC (ethanol casein), CAh (control Ah) and EAh (ethanol Ah). When comparing EAh vs . EC, we found a positive effect of Ah on lipids, preventing the increment of serum cholesterol (p <0.001), through the higher expression of the LDL receptor (p <0.001); and it also decreased free (p < 0.05) and esterified cholesterol (p <0.01) in liver, probably via the reduction of the 3-hydroxy-3-methylglutaryl coenzyme A reductase expression (p <0.001). We also observed that amaranth contributed to the decrease of fat deposits in liver, probably through the decrease in acetyl-CoA carboxylase alpha (p <0.01), glycerol-3-phosphate acyltransferase 1 (p <0.01) and diacylglycerol O-acyltransferase 2 (p <0.05) expression. The histological study showed a decrease in the fat deposits in the amaranth group when compared to casein; this is consistent with the biochemical and molecular parameters studied in this work. In conclusion, amaranth could be recommended to avoid the alterations in the lipid metabolism induced by alcohol and other harmful agents.


Assuntos
Amaranthus/química , Colesterol/metabolismo , Fígado Gorduroso Alcoólico/dietoterapia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fitoterapia , Proteínas de Plantas/uso terapêutico , Tecido Adiposo/metabolismo , Animais , Esterificação , Etanol/efeitos adversos , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/metabolismo , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/genética , Fígado/enzimologia , Fígado/metabolismo , Masculino , Proteínas de Plantas/farmacologia , Ratos , Ratos Wistar , Receptores de LDL/sangue , Sementes/química
9.
Nutrients ; 5(7): 2629-45, 2013 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-23857172

RESUMO

Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.


Assuntos
Apolipoproteína B-100/sangue , Echium/química , Lipólise/efeitos dos fármacos , Óleos de Plantas/farmacologia , Receptores de LDL/sangue , Triglicerídeos/sangue , Animais , Ésteres do Colesterol/sangue , VLDL-Colesterol/sangue , Óleos de Peixe/farmacologia , Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óleo de Palmeira , RNA/genética , RNA/isolamento & purificação
10.
J Nutr ; 137(5): 1165-70, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17449576

RESUMO

We previously demonstrated that a diet therapy involving consumption of 7.28 g psyllium (PSY) and 2 g of plant sterols (PS) per day reduced LDL cholesterol from 3.6 +/- 0.7 to 3.1 +/- 0.8 mmol/L (P < 0.01) and decreased the number of intermediate density lipoprotein particles and the smaller LDL and HDL subfractions in hypercholesterolemic individuals (n = 33). The study design was a randomized double blind crossover. Subjects consumed either 2 test cookies containing PSY+PS or 2 placebo cookies for 1 mo with a 3-wk wash out between treatments. To explore mechanisms of the lipid-lowering effects of combined PSY+PS, we present data related to intravascular and molecular regulation. Intake of PSY+PS decreased the cholesterol concentration in LDL-1 from 2.46 +/- 0.66 to 2.26 +/- 0.46 mmol/L and in LDL-2 from 0.63 +/- 0.24 to 0.54 +/- 0.27 mmol/L (P < 0.05) in the test compared with the placebo period. An increase in LDL peak size from 27.3 +/- 0.8 to 27.5 +/- 0.6 nm (P < 0.05) and a decrease in the prevalence of LDL pattern B from 27 to 18% (P < 0.05) also occurred during the PSY+PS period. Cholesteryl ester transfer protein activity was 11% lower (P < 0.05) during the test period. Notably, the abundance of the LDL receptor in circulating mononuclear cells as measured by real time PCR was 26% higher during the test compared with the placebo period (P < 0.03). These results indicate that the hypocholesterolemic action of PSY and PS can be explained in part by modifications in the intravascular processing of lipoproteins and by increases in LDL receptor-mediated uptake.


Assuntos
Hipercolesterolemia/dietoterapia , Hipercolesterolemia/metabolismo , Hipolipemiantes/farmacologia , Lipoproteínas LDL/metabolismo , Lipoproteínas/metabolismo , Fitosteróis/administração & dosagem , Psyllium/administração & dosagem , Adulto , Idoso , Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Proteínas de Transferência de Ésteres de Colesterol/sangue , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Concentração Osmolar , Oxirredução , Tamanho da Partícula , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Fitosteróis/uso terapêutico , Psyllium/uso terapêutico , RNA Mensageiro/metabolismo , Receptores de LDL/sangue , Receptores de LDL/genética , Fatores de Tempo , Distribuição Tecidual
11.
J Nutr ; 135(9): 2075-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16140878

RESUMO

Dietary fatty acids have a considerable effect on plasma LDL cholesterol (LDL-C) concentrations and therefore on the risk for coronary heart disease. Numerous studies have been conducted in animal models to elucidate the mechanisms by which different types of fatty acids modulate plasma cholesterol concentrations. In addition, multiple clinical trials and epidemiological data have demonstrated the effects of fatty acids in determining the concentrations of circulating LDL. SFAs and trans fatty acids have a detrimental effect on plasma lipids, whereas PUFAs of the (n-6) family and monounsaturated fatty acids decrease plasma LDL-C concentrations. Among the SFAs, stearic acid (18:0) appears to have a neutral effect on LDL-C, while lauric (12:0), myristic (14:0), and palmitic (16:0) acids are considered to be hypercholesterolemic. SFAs increase plasma LDL-C by increasing the formation of LDL in the plasma compartment and by decreasing LDL turnover. Although unsaturated fatty acids increase cholesterol synthesis, they also increase hepatic LDL receptor number and LDL turnover in vivo. Fatty acids are also ligands of important regulatory elements, which can play a role in determining plasma cholesterol. This article presents a summary of the major effects of various types of fatty acids on plasma lipid concentrations and the mechanisms involved.


Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Lipídeos/sangue , Animais , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/sangue , Ácidos Graxos Insaturados/farmacologia , Humanos , Receptores de LDL/sangue
12.
J Nutr ; 133(11): 3588-91, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14608078

RESUMO

An elevated plasma concentration of homocysteine is an independent risk factor for cardiovascular disease. However, the mechanisms are still unclear. Lectin-like oxidized LDL receptor-1 (LOX-1) has ligand specificity for oxidized LDL (oxLDL). We hypothesized that homocysteine's atherogenic effects may involve LOX-1-mediated mechanisms. We examined the effect of folic acid supplementation for 6 wk and 12 mo (5 mg/d for 1 wk, 1 mg/d for 37 wk and 0.4 mg/d for the remaining 14 wk) on LOX-1 mRNA levels and on oxLDL-induced release of tumor necrosis factor alpha from peripheral blood mononuclear cells in hyperhomocysteinemic individuals. Compared with healthy controls, hyperhomocysteinemic subjects had elevated mRNA levels of LOX-1 in mononuclear cells (P < 0.001), and their mononuclear cells released more tumor necrosis factor alpha (TNFalpha) upon oxLDL stimulation (P = 0.01). This oxLDL-stimulated release of TNFalpha correlated with LOX-1 expression (r = 0.57, P = 0.026). Folic acid treatment led to a normalization of homocysteine levels accompanied by a reduction in LOX-1 gene expression (P < 0.02) and in oxLDL-stimulated release of TNFalpha (P < 0.05). These novel findings suggest both that homocysteine exerts its atherogenic effect in part by elevating levels of LOX-1, thereby enhancing oxLDL-induced inflammatory responses, and most important, that folic acid supplementation may downregulate these responses.


Assuntos
Ácido Fólico/farmacologia , Regulação da Expressão Gênica/genética , Hiper-Homocisteinemia/sangue , Leucócitos Mononucleares/fisiologia , Receptores de LDL/sangue , Receptores de LDL/genética , Adulto , Idoso , Feminino , Humanos , Hiper-Homocisteinemia/genética , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Receptores de LDL Oxidado , Receptores Depuradores Classe E , Transcrição Gênica , Fator de Necrose Tumoral alfa/biossíntese
13.
J Nutr ; 133(1): 67-70, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12514268

RESUMO

Psyllium (PSY) intake decreases plasma LDL cholesterol (LDL-C) in men and pre- and post-menopausal women while PSY effects on plasma triglycerides (TG) are sex related. A significant decrease in plasma TG was observed in men while postmenopausal women experienced an increase in plasma TG concentrations following PSY supplementation. To further explore the mechanisms by which sex and hormonal status influence the effects of PSY on plasma lipids, HMG-CoA reductase, LDL receptor and lipoprotein lipase (LPL) mRNA abundance were measured in mononuclear cells isolated from these subjects. The intervention followed a randomized crossover design in which participants were allocated to either 15 or 0 g (control) of PSY/d for 30 d. Compared to the control period, PSY intake induced a 20% increase in HMG-CoA reductase mRNA abundance (P < 0.05) while no significant changes in LDL receptor mRNA abundance were observed. In contrast, LPL mRNA abundance was 24% higher in men and 23% lower in postmenopausal women (P < 0.05) when comparing PSY with the control period. These results suggest that the LDL-C lowering induced by PSY was related to changes in HMG-CoA reductase gene expression in monocytes while the expression of LPL in this system was affected by sex and hormonal status.


Assuntos
LDL-Colesterol/sangue , Lipase Lipoproteica/sangue , Psyllium/farmacologia , Receptores de LDL/sangue , Estudos Cross-Over , Feminino , Humanos , Hidroximetilglutaril-CoA Redutases/sangue , Masculino , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Psyllium/administração & dosagem , Fatores Sexuais
14.
Atherosclerosis ; 150(2): 285-93, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10856520

RESUMO

Despite numerous studies, the precise role of dietary n-6 polyunsaturated fatty acids in the pathogenesis of atherosclerosis remains controversial. It has been shown that feeding an n-6-enriched diet resulted in decreased atherosclerosis in African green monkeys and was associated with a reduction in LDL levels. However, other authors reported that n-6 supplementation increased the oxidative stress and the susceptibility of LDL to undergo in vitro oxidation, thus potentially enhancing atherosclerosis. The present study was designed to investigate the effect of dietary supplementation of n-6 polyunsaturated fats (safflower oil), as compared with a saturated fat-rich diet (Paigen), on the blood lipid profile and atherosclerosis in two mouse models. In the first experiment, female C57BL/6 mice (n=23-30 per group) were fed a cholate containing Paigen diet, a safflower oil-rich diet (with cholate), or normal chow for 15 weeks. No significant differences between the high fat diet groups were evident with respect to total cholesterol, LDL, HDL or triglyceride levels. The extent of aortic sinus fatty streaks did not differ significantly between the two groups. In the second experiment, LDL-receptor-deficient (LDL-RD) mice (n=20-30 per group) were randomized into similar dietary regimens. Mice consuming a safflower oil-enriched diet developed significantly less atherosclerosis, in comparison with Paigen diet-fed mice. A reduction in LDL levels, although not of a similar magnitude as the reduction in atherosclerosis, was evident in the safflower oil-fed mice when compared to the Paigen diet-fed littermates. In both mouse models of atherosclerosis, LDL isolated from the plasma of mice on the n-6 polyunsaturated diet was rendered slightly more susceptible to oxidation in vitro, as indicated by a shorter lag period for diene formation. Thus, the effects of n-6 fatty acids on the lipoprotein composition and other potential influences may have contributed to the anti-atherogenic effect in the LDL-RD mouse model.


Assuntos
Arteriosclerose/dietoterapia , Gorduras Insaturadas na Dieta/administração & dosagem , Suplementos Nutricionais , Ácidos Graxos Insaturados/administração & dosagem , Lipoproteínas LDL/sangue , Estresse Oxidativo/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Arteriosclerose/sangue , Arteriosclerose/induzido quimicamente , Arteriosclerose/patologia , Peso Corporal , Dieta Aterogênica , Progressão da Doença , Ácidos Graxos Ômega-6 , Feminino , Lipoproteínas LDL/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Receptores de LDL/sangue , Receptores de LDL/deficiência , Receptores de LDL/efeitos dos fármacos , Óleo de Cártamo/administração & dosagem , Triglicerídeos/sangue
15.
J Lipid Res ; 39(5): 1079-90, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9610776

RESUMO

Probucol is a powerful inhibitor of atherosclerosis in a number of animal models. However, it is unknown whether this is due to the strong antioxidant protection of low density lipoprotein (LDL), to antioxidant effects in the artery wall, or to cellular effects not shared by other antioxidants. To investigate whether murine models are suitable to study the antiatherogenic mechanisms of probucol, three experiments following different protocols were carried out in 135 male and female LDL receptor-deficient (LDLR-/-) mice. Treatment groups received a high (0.5%) or low (0.025%) dose of probucol, or low-dose probucol plus a high dose (0.1%) of vitamin E for periods ranging from 6 to 26 weeks. In all experiments, probucol strongly protected LDL against ex vivo oxidation (lag times exceeding 1400 min in 0.5% probucol-treated mice). Treatment with 0.5% probucol significantly lowered both HDL-cholesterol and plasma apolipoprotein (apo)A-I concentrations. In all three experiments, treatment with 0.5% probucol consistently increased the size of lesions in the aortic origin, from 1.3-fold (n.s.) to 2.9-fold (P < 0.05) in female mice and from 3.6- to 3.7-fold in males (P < 0.001). Even treatment with 0.025% probucol increased atherosclerosis 1.6-fold in male mice (P < 0.01). Addition of the high dose of vitamin E did not attenuate the pro-atherogenic effect of 0.025% probucol. In conclusion, probucol not only failed to decrease but actively increased atherogenesis in LDLR-/- mice in a dose-dependent manner, even though it provided a very strong antioxidant protection of LDL. This suggests that the reduction of atherosclerosis observed in other animal models is due to intracellular effects of probucol not found in mice, to differences in the metabolism of probucol, and/or to an overriding atherogenic effect of the decrease in HDL in murine models.


Assuntos
Anticolesterolemiantes/farmacologia , Arteriosclerose/sangue , Lipoproteínas LDL/sangue , Probucol/farmacologia , Receptores de LDL/fisiologia , Animais , Anticolesterolemiantes/sangue , Colesterol na Dieta/sangue , Colesterol na Dieta/farmacologia , Feminino , Lipoproteínas HDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Probucol/sangue , Receptores de LDL/sangue , Vitamina E/sangue , Vitamina E/farmacologia
16.
Lipids ; 33(12): 1177-86, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9930403

RESUMO

We investigated the possibility that dietary cholesterol downregulates the expression of low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase genes of circulating mononuclear cells in vivo in healthy humans. We also studied the variations of the LDL receptor-related protein (LRP) gene in the same conditions. Dieters (n = 5) were submitted to a 4-d fat restriction (mean cholesterol intake: 6+/-4 mg/d), followed by a 7-d cholesterol (a mean of 791+/-150 mg/d) supplementation. Controls (n = 3) did not change their diet. During fat restriction, serum total and LDL cholesterol decreased significantly (P < 0.05), and LDL receptor and HMG-CoA reductase mRNA copy numbers in mononuclear cells increased by 57 and 147%, respectively (P < 0.05). After reintroducing cholesterol, serum cholesterol was stable whereas LDL receptor and HMG-CoA reductase mRNA decreased by 46 and 72% (P < 0.05) and LRP mRNA increased by 59% (P < 0.005). The changes in LDL receptor and HMG-CoA reductase mRNA abundance were correlated (r = +0.79, P = 0.02) during cholesterol reintroduction as were LDL receptor and LRP mRNA levels, but negatively (r = -0.70, P = 0.05). Also, 70% of the variability in LRP mRNA (P < 0.005) was explained by dietary cholesterol. Thus, the basic mechanisms regulating cellular cholesterol content, the coordinate feedback repression of genes governing the synthesis and uptake of cholesterol, are operating in vivo in humans. However, serum cholesterol did not increase in response to dietary cholesterol, suggesting that these mechanisms may not play as predominant a role as previously believed in the short-term control of serum cholesterol in vivo in humans. A new finding is that LRP gene is also sensitive to dietary cholesterol, suggesting that it may participate in the control of serum cholesterol. Further in vivo studies in humans are warranted to explore the molecular mechanisms of the physiological response to dietary cholesterol in humans.


Assuntos
Colesterol na Dieta/administração & dosagem , Hidroximetilglutaril-CoA Redutases/sangue , RNA Mensageiro/genética , Receptores Imunológicos/sangue , Receptores de LDL/sangue , Adulto , Sequência de Bases , Primers do DNA , Ácidos Graxos/sangue , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Masculino , Pessoa de Meia-Idade , Receptores Imunológicos/genética , Receptores de LDL/genética , Valores de Referência
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