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1.
Clin Sci (Lond) ; 134(2): 273-287, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31957803

RESUMO

The current main treatment for coronary artery disease (CAD) is to reduce low-density lipoprotein cholesterol (LDL-C) by statins, which could decrease the incidence of major adverse cardiovascular events (MACEs) by 30%. However, many residual risks still remain. To clarify the mechanism involved, we studied patients with acute myocardial infarction (AMI) with low LDL-C levels. Lymphocytes were isolated, and it was found that despite no difference in plasma LDL-C level, the lymphocyte cholesterol content was higher in AMI patient than those in non-CAD patients; thus, the decrease in intracellular cholesterol content was inconsistent with that in the plasma. Additionally, [3H]-cholesterol efflux rates were lower and mRNA levels of the inflammatory factors tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) higher in AMI lymphocytes. It was found that sulphotransferase 2B1b (SULT2B1b) expression was higher in AMI lymphocytes. Further research using Jurkat T lymphocytes confirmed that SULT2B1b knockdown increased cholesterol efflux capacity and decreased mRNA levels of TNF-α and IFN-γ by increasing liver X receptor (LXR)-ß levels. Furthermore, the degree of CpG island methylation in the SULT2B1b promoter was reduced in cells from AMI patients. In conclusion, SULT2B1b up-regulation due to hypomethylation of its promoter promotes cholesterol accumulation and inflammation by inhibiting LXR-ß in lymphocytes of AMI patients with low LDL-C levels. Therefore, reducing intracellular cholesterol is also important as plasma cholesterol levels. Therapeutic approaches to decrease SULT2B1b expression might be potentially beneficial for CAD prevention by decreasing intracellular cholesterol.


Assuntos
Colesterol/metabolismo , Interferon gama/metabolismo , Linfócitos/metabolismo , Sulfotransferases/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Transporte Biológico , Colesterol/sangue , LDL-Colesterol/metabolismo , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/prevenção & controle , Metilação de DNA , Humanos , Mediadores da Inflamação/metabolismo , Interferon gama/genética , Células Jurkat , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Regiões Promotoras Genéticas/genética , Sulfotransferases/genética , Fator de Necrose Tumoral alfa/genética
2.
J Agric Food Chem ; 67(48): 13307-13317, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679333

RESUMO

Epidemiological studies have demonstrated that hypercholesterolemia is associated with an elevated risk of atherosclerosis and cardiovascular diseases. In addition to the available cholesterol-lowering drugs, nutritionally balanced diets containing functional foods have attracted much interest as potential candidates to improve hypercholesterolemia. In the study, we demonstrated that dietary succinoglycan riclin effectively alleviated diet-induced hypercholesterolemia. Compared with the high-cholesterol-diet (HCD) group, the high-riclin group significantly decreased levels of the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and hepatic cholesterol (34, 40, and 51%, respectively), consequently improving hepatic steatosis and reducing proinflammatory cytokine expressions. 1H nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analyses revealed that the riclin group partially reversed metabolic profile changes induced by the HCD, approaching that of the normal diet (ND) group. Riclin has no direct effects on cholesterol metabolism-related gene expression among the three HCD model groups. Basically, riclin increased the solution viscosity and interfered in the process of bile acid-cholesterol emulsification, decreasing cholesterol digestion and promoting cholesterol and bile acid excretion in the feces. These results suggested potential therapeutic utility of succinoglycan riclin as a food additive for people suffering from hypercholesterolemia and related diseases.


Assuntos
Anticolesterolemiantes/metabolismo , Hipercolesterolemia/dietoterapia , Polissacarídeos Bacterianos/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
3.
World J Gastroenterol ; 25(38): 5826-5837, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31636475

RESUMO

BACKGROUND: Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus (HCV). APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection. The relationship between cholesterol, APOE alleles, and the outcome of HCV infection has not been evaluated in the admixed population of Mexico. AIM: To investigate the role of APOE -ε2, -ε3, and -ε4 alleles and the metabolic profile in the outcome of HCV infection. METHODS: A total of 299 treatment-naïve HCV patients were included in this retrospective study. Patients were stratified in chronic hepatitis C (CHC) (n = 206) and spontaneous clearance (SC) (n = 93). A clinical record was registered. Biochemical tests were assessed by dry chemistry assay. APOE genotypes were determined using a Real-Time polymerase chain reaction assay. RESULTS: Total cholesterol, low-density lipoprotein cholesterol (LDL-c), triglycerides, and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOE ε4 allele (12.4% vs 7.3%). SC patients were overweight (54.8%). The ε4 allele was associated with SC (OR = 0.55, 95%CI: 0.31-0.98, P = 0.042) and mild fibrosis (F1-F2) in CHC patients (OR 0.091, 95%CI 0.01-0.75, P = 0.020). LDL-c ≥ 101.5 mg/dL (OR = 0.20, 95%CI: 0.10-0.41, P < 0.001) and BMI ≥ 26.6 kg/m2 (OR= 0.37, 95%CI: 0.18-0.76, P < 0.001) were associated with SC status; while ALT ≥ 50.5 IU/L was negatively associated (OR = 5.67, 95%CI: 2.69-11.97, P < 0.001). CONCLUSION: In SC patients, the APOE ε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.


Assuntos
Apolipoproteínas E/genética , LDL-Colesterol/sangue , Hepatite C/genética , Hipercolesterolemia/metabolismo , Sobrepeso/metabolismo , Adulto , Alelos , Apolipoproteínas E/metabolismo , Peso Corporal , LDL-Colesterol/metabolismo , Feminino , Hepacivirus/isolamento & purificação , Hepacivirus/metabolismo , Hepacivirus/patogenicidade , Hepatite C/sangue , Hepatite C/virologia , Interações Hospedeiro-Patógeno/genética , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/genética , Masculino , México , Pessoa de Meia-Idade , Sobrepeso/sangue , Sobrepeso/genética , Polimorfismo Genético , Fatores de Proteção , Remissão Espontânea , Estudos Retrospectivos , Carga Viral/genética
4.
Food Funct ; 10(11): 6987-6998, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31637390

RESUMO

Cardiovascular disease (CVD) is the greatest cause of premature death and disability globally. Consequently, numerous therapeutic strategies have been developed in order to prevent the onset of adverse cardiovascular events including nutritional approaches. This includes strawberries as they have a high oxidant and micronutrient content, so we examined the extent to which dietary supplementation impacts on CVD risk factors. A comprehensive literature search without any limitation on language was conducted using the following bibliographical databases: ISI Web of Science, Scopus, PubMed and Cochrane Library. Search was conducted between 1985 and February 2019. The mean difference (MD) of the reported effects was calculated using a random effect model. A total of 20 groups from 14 clinical trials were included for final analysis. The pooled effect size showed that strawberry supplementation decreased circulating oxidized LDL (MD = -5.8 ng ml-1, p = 0.012), malondialdehyde (0.309 µmol L-1, p = 0.002), C-reactive protein (MD = -0.472 mg L-1, p = 0.003), total cholesterol (MD = -6.49 mg dL-1, p = 0.019), and diastolic blood pressure (MD = -2.220 mmHg, p = 0.033). It also demonstrated raised fasting blood sugar (MD = 2.083 mg dl-1; p = 0.040), but had no effect on other CVD risk factors examined. Dietary supplementation with strawberries improved specific CVD risk factors, suggesting that larger well-designed, adequately powered, and longer-term follow up studies should now be undertaken.


Assuntos
Doenças Cardiovasculares/dietoterapia , Fragaria/metabolismo , Adulto , Pressão Sanguínea , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Feminino , Fragaria/química , Frutas/química , Frutas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
5.
Biol Pharm Bull ; 42(10): 1628-1636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582651

RESUMO

Cigarette smoke extract (CSE) contains many toxicants and may derange the physiological processes, such as cholesterol metabolism. We examined the impact of CSE on transcriptional regulation mediated peroxisome proliferator-activated receptors (PPARs) and its interaction with cofactors to elucidate differences in the molecular mechanism between CSE and other agonists of PPARs. We constructed several mutant PPARs (mPPARs) with amino acid substitution in the ligand-binding domain, which according to the molecular modeling, may affect the binding of agonists. In transient expression assays, each wild-type peroxisome proliferator-activated receptor (PPAR) mediated transcription stimulated by CSE was faintly yet significantly elevated compared to the control. The CSE-induced transcriptional activation was abolished in the H323A, H323Y, S342A, and H449A mPPARγs, although the activation elevated by pioglitazone was reserved. In the mPPARγ with Y473A and mPPARß/δs with H286Y and Y436A, the pioglitazone-induced or L165041-activated transcriptional elevations were decreased and were lower than that of CSE-induced stimulation. These results suggested that CSE activated both mutant PPARs to be selectively different from those ligands. Mammalian two-hybrid assay illustrated that CSE could mildly recruit SRC1 or GRIP1 to the wild-type PPARγ. Representative ingredients, such as acrolein and crotonaldehyde present in CSE, could stimulate PPAR isoforms even at the toxicological concentrations and might possibly contribute to stimulatory effects. CSE mildly regulates the cholesterol metabolism-related genes, such as low density lipoprotein (LDL) receptor and Liver X receptor (LXR)ß. In conclusion, these CSE effects the nuclear hormone receptors and their cofactors thereby disturbing metabolic phenomena. Therefore, CSE might be involved in cholesterol metabolism.


Assuntos
Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Fumaça , Tabaco , Substituição de Aminoácidos , Linhagem Celular , LDL-Colesterol/metabolismo , Humanos , Receptores X do Fígado/genética , Receptores Ativados por Proliferador de Peroxissomo/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores de LDL/genética
6.
Biochimie ; 167: 145-151, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586653

RESUMO

The research literature on atherosclerosis includes findings investigating the atherosclerotic effect of oxysterols, which are the oxidation products of cholesterol; and the literature on oxysterols refers to mechanisms by which oxysterols cause phospholipid packing defects in cell membranes. This review synthesizes these two bodies of research findings to describe how oxysterols cause phospholipid packing defects within the membranes of vascular endothelial cells, potentially increasing cell permeability of low-density lipoprotein cholesterol which may lead to atheroma formation. Exogenous sources of oxysterols are provided by dietary intake of animal-based foods that contain cholesterol oxidation products. This review proposes an explanation for the anti-atherosclerotic effect of plant-based dietary patterns, which is attributed to restriction or avoidance of dietary oxysterol intake from animal-based foods. Furthermore, raw-milk cheeses play an important role in the traditional French diet-low oxysterol content in these unheated foods may contribute to the French paradox, in which reduced coronary heart disease is associated with a diet high in saturated fat and cholesterol.


Assuntos
Aterosclerose , LDL-Colesterol/metabolismo , Células Endoteliais/metabolismo , Membranas/metabolismo , Oxisteróis/metabolismo , Fosfolipídeos/metabolismo , Aterosclerose/dietoterapia , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Dieta , Células Endoteliais/citologia , Humanos , Oxirredução , Compostos Fitoquímicos/farmacologia
7.
J Agric Food Chem ; 67(43): 11922-11930, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31576748

RESUMO

We investigated the regulatory effects of citrus pectin oligosaccharides (POS) from an innovative, chemically controllable degradation process on cholesterol metabolism and the gut microbial composition. The modulatory role of the intestinal flora was explored. Four-week-old male C57BL/6 mice were fed either a standard diet; a high-fat (HF) diet; or a HF diet with 0.15, 0.45, and 0.9 g/kg body weight POS for 30 days. POS reduced serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) in a dose-dependent manner. The relative abundances of specific bacterial groups in the feces and the concentrations of their metabolites were higher in the POS groups. There were significant correlations among Bifidobacterium, Lactobacillus, and Bacteroides and short-chain fatty acids, as well as among serum TC, LDL-C, fecal bile acids, and liver cholesterol 7-α-hydroxylase and 3-hydroxy-3-methylglutaryl-coenzyme A reductase. These findings indicate that the prepared POS exhibited hypocholesterolemic effects and that the potential regulatory mechanisms of citrus POS on cholesterol metabolism are modulated by specific bacterial groups together with their metabolites.


Assuntos
Anticolesterolemiantes/administração & dosagem , Colesterol/metabolismo , Citrus/química , Microbioma Gastrointestinal , Hipercolesterolemia/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Pectinas/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Humanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
J Oleo Sci ; 68(9): 909-922, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31484903

RESUMO

The objective of this research was to evaluate the effect of wheat gluten on gut microbiota from hamsters and also analyse whether alterations in microbiota could result in wheat gluten's lipid-lowering properties. Four weeks male hamsters were divided into 3 groups (n=10). Two hypercholesterolemic groups were fed for 35 days with hypercholesterolemic diet, containing 20% (w/w) wheat gluten or casein. Wheat gluten significantly reduced serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) concentrations, and also decreased the liver total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE), triglycerides (TG) concentrations. Wheat gluten group had a higher fecal lipids, total cholesterol (TC) and bile acids (BA) than that of casein group (p < 0.05). Moreover, wheat gluten significantly increased total short-chain fatty acids (SCFA) concentrations in feces. Sequencing of 16S rRNA gene revealed that intake of wheat gluten decreased the relative abundances of Firmicutes and Erysipelotrichaceae, but to increased the relative abundances of Bateroidetes, Bacteroidales_S24-7_group and Ruminococcaceae. The lipid lowering properties of wheat gluten was associated with the lower ratio of Firmicutes/Bateroidetes, the lower of the bacterial taxa Erysipelotrichaceae and the higher of the bacterial taxa Bacteroidales_S24-7_group and Ruminococcaceae. These results suggest that wheat gluten modulate cholesterol metabolism by altering intestinal microflora.


Assuntos
Anticolesterolemiantes/farmacologia , LDL-Colesterol/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Glutens/farmacologia , Hiperlipidemias/microbiologia , Triticum/química , Animais , LDL-Colesterol/sangue , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Masculino , Mesocricetus , RNA Ribossômico 16S/análise
10.
Food Funct ; 10(9): 5290-5301, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31475703

RESUMO

High consumption of cooking oils in modern society is believed to be the major cause of cardiovascular disease. The effect of cooking oils depends on their fatty acid composition. Therefore, it is important to blend different types of oils to improve functional properties. In this study we evaluated the effects of a functional blended oil (BO) composed of a high level of oleic acid (OA) (50.93%) and α-linolenic acid (ALA) (5.41%) on cardiovascular health, blood pressure (BP) and body weight (BW) in comparison with lard oil (LO) and peanut oil (PO). Ninety male Wistar rats were divided into three groups and fed for 12 weeks with BO, LO and PO. Each group was divided into low, middle and high fat groups and fed with oil supply ratios of 6.7%, 10.9% and 48.1%, respectively. After the feeding period, the rats were sacrificed, and data were collected and analyzed. Rats treated with BO especially at a high dose (HBO) showed a significantly lower body weight, fat weight, liver weight, fat ratio, food intake and energy intake. BO significantly reduced n-6/n-3 levels in plasma, liver and adipose tissues as well as serum triglycerides (TGs) and low density lipoprotein cholesterol (LDL-C) but contrarily increased high density lipoprotein cholesterol (HDL-C). Furthermore, HBO treatments decreased mRNA expression of lipid anabolism-related genes, lipid inflammatory-related genes, toll-like receptor 4 (TLR4), nuclear factor kappa beta (NF-κB) and monocyte chemoattractant protein (MCP)-1 and increased lipid catabolism-related genes as well as peroxisome proliferator-activated receptor gamma mRNA (PPARγ mRNA). In terms of antioxidant enzymes, BO treatment has increased the activity of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) by lowering malondialdehyde (MDA) and reactive oxygen species (ROS) in tissues. Moreover, BO supplementation showed a significant lowering effect on the serum levels of C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α), blood pressure (BP), atherosclerosis index (AI) and heart rate (HR). These findings highlight that the new blend of canola oil, corn oil, olive oil, peanut oil and sunflower oil with a low n-6/n-3 PUFA ratio of 6 : 1 could prevent and control cardiovascular disease (CVD).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Obesidade/dietoterapia , Óleos Vegetais/metabolismo , Animais , Pressão Sanguínea , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Catalase/genética , Catalase/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Humanos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Ácido Oleico/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Óleos Vegetais/química , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Triglicerídeos/metabolismo , Ácido alfa-Linoleico/metabolismo
11.
Nat Commun ; 10(1): 3521, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387993

RESUMO

The intracellular transport of cholesterol is subject to tight regulation. The structure of the lysosomal integral membrane protein type 2 (LIMP-2, also known as SCARB2) reveals a large cavity that traverses the molecule and resembles the cavity in SR-B1 that mediates lipid transfer. The detection of cholesterol within the LIMP-2 structure and the formation of cholesterol-like inclusions in LIMP-2 knockout mice suggested the possibility that LIMP2 transports cholesterol in lysosomes. We present results of molecular modeling, crosslinking studies, microscale thermophoresis and cell-based assays that support a role of LIMP-2 in cholesterol transport. We show that the cavity in the luminal domain of LIMP-2 can bind and deliver exogenous cholesterol to the lysosomal membrane and later to lipid droplets. Depletion of LIMP-2 alters SREBP-2-mediated cholesterol regulation, as well as LDL-receptor levels. Our data indicate that LIMP-2 operates in parallel with Niemann Pick (NPC)-proteins, mediating a slower mode of lysosomal cholesterol export.


Assuntos
Antígenos CD36/metabolismo , LDL-Colesterol/metabolismo , Glicoproteínas de Membrana Associadas ao Lisossomo/metabolismo , Lisossomos/metabolismo , Receptores Depuradores/metabolismo , Animais , Antígenos CD36/genética , Células CHO , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cricetulus , Fibroblastos , Técnicas de Inativação de Genes , Células HeLa , Humanos , Gotículas Lipídicas/metabolismo , Glicoproteínas de Membrana Associadas ao Lisossomo/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Domínios Proteicos , RNA Interferente Pequeno/metabolismo , Receptores Depuradores/genética
12.
J Oleo Sci ; 68(9): 811-816, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31413246

RESUMO

Cardiovascular disease (CVD) has emerged as the leading cause of dealth worldwide today. Lowering circulating total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) is one of the most effective approaches of CVD prevention. Dietary guidelines and health organizations approved using plant sterols (PS) as the alternative to conventional method in attenuating circulating TC and LDL-C levels and risk of CVD. However, current findings apprear to be controversial on the efficacy of PS. Giving the rise of the field "Nutrigenetics", single nucleotide polymorphisms (SNPs) such as CYP7A1-rs3808607 have been identified that strongly associate with cholesterol metabolism in response to PS intake, towards causing inter-individual variations. This review article aims to discuss the efficacy of dietary PS in managing cholesterol levels based on findings from recent studies. The scope includes reviewing evidence on supporting the efficacy, the metabolic claims, inter-individual variations as well as sitosterolemia associated with PS intake.


Assuntos
Anticolesterolemiantes/uso terapêutico , Fitosteróis/uso terapêutico , Animais , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/dietoterapia , Colesterol/sangue , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Humanos , Fitosteróis/efeitos adversos , Polimorfismo de Nucleotídeo Único
13.
Curr Med Chem ; 26(37): 6704-6723, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31438826

RESUMO

Dietary phytosterols, which comprise plant sterols and stanols, reduce plasma Low-Density Lipoprotein-Cholesterol (LDL-C) levels when given 2 g/day. Since this dose has not been reported to cause health-related side effects in long-term human studies, food products containing these plant compounds are used as potential therapeutic dietary options to reduce LDL-C and cardiovascular disease risk. Several mechanisms have been proposed to explain the cholesterol-lowering action of phytosterols. They may compete with dietary and biliary cholesterol for micellar solubilization in the intestinal lumen, impairing intestinal cholesterol absorption. Recent evidence indicates that phytosterols may also regulate other pathways. Impaired intestinal cholesterol absorption is usually associated with reduced cholesterol transport to the liver, which may reduce the incorporation of cholesterol into Very-Low- Density Lipoprotein (VLDL) particles, thereby lowering the rate of VLDL assembly and secretion. Impaired liver VLDL production may reduce the rate of LDL production. On the other hand, significant evidence supports a role for plant sterols in the Transintestinal Cholesterol Excretion (TICE) pathway, although the exact mechanisms by which they promote the flow of cholesterol from the blood to enterocytes and the intestinal lumen remains unknown. Dietary phytosterols may also alter the conversion of bile acids into secondary bile acids, and may lower the bile acid hydrophobic/hydrophilic ratio, thereby reducing intestinal cholesterol absorption. This article reviews the progress to date in research on the molecular mechanisms underlying the cholesterol-lowering effects of phytosterols.


Assuntos
LDL-Colesterol/antagonistas & inibidores , Fitosteróis/farmacologia , Animais , Ácidos e Sais Biliares/antagonistas & inibidores , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/metabolismo , LDL-Colesterol/química , LDL-Colesterol/metabolismo , Suplementos Nutricionais , Humanos , Estrutura Molecular , Fitosteróis/administração & dosagem , Fitosteróis/química
14.
Nutr Metab Cardiovasc Dis ; 29(11): 1245-1253, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31439394

RESUMO

BACKGROUND AND AIMS: The novel nutraceutical combination containing red yeast rice (monacolin K 3.3 mg), Berberis aristata cortex extract (Berberine 531.25 mg) and Morus alba leaves extract (1-deoxynojirimycin 4 mg) is effective in the management of elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The aim of the present study was to investigate the effects of the three components on proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of LDL receptor (LDLR) expression, in hepatocyte cell lines and to compare their effects on LDL cellular uptake. METHODS AND RESULTS: HepG2 and Huh7 cells were incubated with B. aristata cortex extract (BCE), red yeast rice (RYR) and M. alba leaves extract (MLE) alone or in combination for 24 h. RYR (50 µg/mL) increased PCSK9 protein expression (Western blot analysis and ELISA), PCSK9 mRNA (qPCR) and its promoter activity (luciferase reporter assay). BCE (40 µg/mL) reduced instead PCSK9 expression, mRNA levels and promoter activity. MLE determined a concentration-dependent reduction of PCSK9 at the mRNA and protein levels, with a maximal reduction at 1 mg/mL, without significant changes of PCSK9 promoter activity. MLE also downregulated the expression of 3-hydroxy-3-methyl-3-glutaryl coenzyme A reductase and fatty acid synthase mRNA levels. The combination of RYR, BCE and MLE reduced the PCSK9 mRNA and protein levels, as well as the promoter activity. Finally, the single components and their combination induced LDL receptor and LDL uptake by the hepatocytes. CONCLUSION: The positive effect of MLE on PCSK9 supports the rationale of using the nutraceutical combination of RYR, BCE and MLE to control hyperlipidemic conditions.


Assuntos
Anticolesterolemiantes/farmacologia , Berberis/química , Produtos Biológicos/farmacologia , LDL-Colesterol/metabolismo , Hepatócitos/efeitos dos fármacos , Lovastatina/farmacologia , Morus/química , Extratos Vegetais/farmacologia , Pró-Proteína Convertase 9/metabolismo , Anticolesterolemiantes/isolamento & purificação , Relação Dose-Resposta a Droga , Regulação para Baixo , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Regulação Enzimológica da Expressão Gênica , Células Hep G2 , Hepatócitos/enzimologia , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Pró-Proteína Convertase 9/genética
15.
Med Sci Monit ; 25: 5934-5941, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397429

RESUMO

BACKGROUND The impact of low-density lipoprotein cholesterol (LDL-C) levels on outcomes in patients with non-diabetic acute ischemic stroke remains uncertain. The objective of this study was to explore whether LDL-C could refine outcomes after acute ischemic stroke in patients with non-diabetic acute ischemic stroke. MATERIAL AND METHODS A multi-center, retrospective, clinical-based study was conducted within eight hospitals between January 2015 and August 2016. Adjusted odds ratio (aOR) was used for measurement of unfavorable outcome which was evaluated by the modified Rankin Scale (mRS) score at 6 months after acute ischemic stroke, estimated categorically according to multivariate logistic regression. RESULTS A total of 1614 participants with non-diabetic acute ischemic stroke were enrolled, of which 376 patients (23.3%) had unfavorable neurologic outcomes at 6 months. After multivariate analysis comparing 4 LDL-C levels by quartiles (Q), we found that compared to Q1 (LDL-C level ≤2.41 mmol/L), there was a significant association between the frequency of unfavorable outcomes and levels of LDL-C (Q3: 2.95-3.54 mmol/L) for all participants (adjusted odds ratio [aOR]=0.63; 95% CI: 0.44-0.92, P=0.016) and patients with first ever strokes (aOR=0.52; 95% CI: 0.31-0.87, P=0.013). CONCLUSIONS Compared to lower LDL-C levels, non-diabetic patients with LDL-C levels in Q3 (2.95-3.54 mmol/L), were less likely to have unfavorable functional outcomes at 6 months after acute ischemic stroke. Managing HDL-C is one of the most important steps for the recovery of acute ischemic stroke.


Assuntos
LDL-Colesterol/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etiologia , Isquemia Encefálica/metabolismo , China , LDL-Colesterol/metabolismo , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
16.
Folia Med (Plovdiv) ; 61(2): 231-239, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301656

RESUMO

BACKGROUND AND AIMS: An important factor in the development of vascular wall lesions is the degradation of the major protein of connective tissue - type IV collagen. Type IV collagen peptides (CIVDP) derived from this degradation are present in the circulation and are a stimulus for production of anti-collagen type IV antibodies (ACIVAbs) IgM, IgG and IgA. The aim of this study was to find a possible association between ACIVAbs, lipid indices and the development of microvascular complications. MATERIALS AND METHODS: Sera of 93 patients (mean age 61.4±11.3 yrs, diabetes duration 9.88±3.12 yrs; hypertension duration 9.28±4.98) with type 2 diabetes mellitus (T2DM) and arterial hypertension (AH) were investigated. ACIVAbs was determined using ELISA and then compared to serum ACIVAbs in 42 age- and sex-matched controls. Diabetics were divided into two groups according to presence (group 1, n=67) or absence (group 2, n=26) of microangiopathy. Lipid profile and lipid indices (log TG/HDL, LDL/HDL, TC/HDL and TG/HDL) were examined too. RESULTS: Patients with T2DM and AH showed statistically significant higher levels of serum ACIVAbs IgG than healthy controls [0.298 (0.237÷0.381) vs 0.210 (0.149÷0.262), KW=14.01, p<0.0001]. Group 1 had statistically significant higher levels of ACIVAbs IgG than patients without microangiopathy [0.323 (0.243÷0.391) vs 0.241 (0.207÷0.291), KW=7.66, p=0.006] and healthy controls [0.210 (0.149÷0.262), KW=17.52, p<0.0001). ACIVAbs IgG showed correlation with duration of diabetes (r=0.49, p=0.01), retinopathy (r=-0.20, p=0.04) and BMI (r=-0.24, p=0.05), HbA1c (r=0.21, p=0.04), SBP (r=0.16, p=0.05). ACIVAbs IgG correlated with log TG/HDL (r=0.21, p=0.01), LDL/HDL (r=0.19, p=0.02) TC/HDL (r=0.16, p=0.05) and with TG/HDL (r=0.15, p=0.05). CONCLUSION: Our study shows relationship between elevation of ACIVAbs IgG, high lipid indices and development of microvascular complications in patients with type 2 diabetes mellitus and arterial hypertension.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Neuropatias Diabéticas/metabolismo , Retinopatia Diabética/metabolismo , Hipertensão/metabolismo , Idoso , Autoanticorpos/imunologia , Estudos de Casos e Controles , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Colágeno Tipo IV/imunologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/imunologia , Angiopatias Diabéticas/metabolismo , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/imunologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/imunologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Triglicerídeos/metabolismo
18.
Gene ; 712: 143911, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31176730

RESUMO

MicroRNA-23b (miR-23b) is associated with inflammation and autoimmune diseases. This study evaluated miR-23b expression and assessed its potential as a biomarker of disease activity for rheumatoid arthritis (RA). Differential expression of microRNAs was determined by miRNA microarray analysis in fibroblast-like synoviocytes (FLSs) from four trauma patients as healthy controls (HCs) and eight RA patients. The microarray results showed elevated expression of miR-23b in FLSs from RA patients and this finding was corroborated by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization using synovial tissues (STs). Furthermore, we found miR-23b levels in plasma of RA patients were significantly higher than in HCs, and plasma miR-23b levels positively correlated with the erythrocyte sedimentation rate (ESR), hypersensitive C-reactive protein (hs-CRP), C-reactive protein (CRP), DAS28, and platelet (PLT) count (P < 0.05). MiR-23b levels in plasma inversely correlated with the levels of hemoglobin (Hb), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), but not with rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA) (P > 0.05). Moreover, patients with anorexia showed higher levels of miR-23b in plasma than those without anorexia. Similar results were observed with fatigue. Appropriate treatment for RA not only ameliorated the disease condition but also reversed the elevated plasma miR-23b level remarkably. These results suggest that circulating miR-23b may be a promising biomarker for RA disease activity.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/genética , MicroRNAs/sangue , Adulto , Idoso , Anticorpos Anti-Proteína Citrulinada/metabolismo , Bilirrubina/química , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Feminino , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hemoglobinas/química , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Contagem de Plaquetas , Fator Reumatoide/metabolismo , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo
19.
JAMA Netw Open ; 2(6): e195844, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31199452

RESUMO

Importance: The prevalence of high-intensity binge drinking (HIBD), defined as consuming 2 or more times the binge threshold defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), is rapidly increasing in the United States. While the relationship between alcohol consumption and lipid and liver function enzyme (LFT) biomarkers has been previously examined, the associations of HIBD with those biomarkers remain unknown. Objective: To examine associations of HIBD with lipid and LFT levels in a cross-sectional sample enriched with participants who engage in HIBD. Design, Setting, and Participants: Cross-sectional study using data from the NIAAA clinical sample collected from March 3, 2005, to August 21, 2017, with participants recruited for either the NIAAA screening protocols or inpatient alcohol treatment program. For this study, participants were stratified by self-reported alcohol consumption into 4 sex-specific binge levels: nonbinge and 1, 2, and 3 or more times the binge threshold (levels I, II, and III). Multivariable analyses examined the odds of clinically high levels of lipids and LFTs across binge levels. Analyses were performed from December 3, 2018, to January 30, 2019. Main Outcomes and Measures: Serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase. Results: A total of 2065 participants underwent protocol screening; 1519 with data available on alcohol consumption, body mass index, lipid levels, and LFT levels were included in the final analyses. Mean (SD) age was 39.7 (12.1) years; mean (SD) body mass index was 26.6 (5.1); 978 (64.4%) were male; 718 (47.3%) were white; and 578 (31.1%) consumed alcohol at the nonbinge level, 321 (21.2%) at level I, 239 (15.7%) at level II, and 318 (25.1%) at level III. High-intensity binge drinking was associated with 2- to 8-fold increased odds for clinically high levels of HDL-C, total cholesterol, triglycerides, and all LFTs (eg, for HDL-C: level III odds ratio [OR], 8.65; 95% CI, 4.75-15.77 and for γ-glutamyltransferase: level III OR, 8.21; 95% CI, 5.90-11.43). Increased HIBD frequency (days consuming at levels II and III) was associated with increased odds for clinically high levels of HDL-C, total cholesterol, and all LFTs (per unit increase in days consuming at the respective binge level) (eg, for HDL-C: level II OR, 1.025; 95% CI, 1.014-1.036 and level III OR, 1.033; 95% CI, 1.019-1.047 and for γ-glutamyltransferase: level II OR, 1.028; 95% CI, 1.019-1.037 and level III OR, 1.033; 95% CI, 1.019-1.047). Conclusions and Relevance: High-impact binge drinking was significantly associated with increased odds for clinically high levels of lipids and LFTs. Given that HIBD is increasingly common among US adults, targeted interventions aimed at reducing HIBD may have important health benefits.


Assuntos
Bebedeira/fisiopatologia , Metabolismo dos Lipídeos/fisiologia , Transferases/metabolismo , Adulto , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Bebedeira/sangue , Bebedeira/enzimologia , Biomarcadores/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Estudos Transversais , Feminino , Humanos , Fígado/enzimologia , Testes de Função Hepática , Masculino , Triglicerídeos/metabolismo , gama-Glutamiltransferase/metabolismo
20.
Food Funct ; 10(6): 3660-3670, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31166330

RESUMO

In this study, we investigated the effects of a newly synthesized α-galacto-oligosaccharide mixture (α-GOSg), 0.5% in drinking water, on high-fat/western-style diet (HFWD)-induced metabolic abnormality in mice in a study of 13 weeks. Raffinose family oligosaccharides (RFOs) were included as a comparison. Mice treated with α-GOSg had significantly lower body weight and body fat (p < 0.05), while RFOs were less effective. Both α-GOSg and RFOs significantly reduced serum levels of total cholesterol and low-density lipoprotein cholesterol, alanine aminotransferase and liver lipids. However, only α-GOSg significantly decreased the histopathological score for liver steatosis and downregulated hepatic fatty acid synthesis gene acetyl CoA carboxylase-α. α-GOSg also significantly reduced the content of bile acids in the small intestine and significantly increased the abundance of gut Bifidobacterium and decreased the abundance of Clostridium leptum. These actions are proposed to be key mechanisms contributing to the beneficial health effects of α-GOSg.


Assuntos
Síndrome Metabólica/prevenção & controle , Oligossacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Camundongos , Camundongos Endogâmicos C57BL
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