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1.
J Food Sci ; 84(8): 2330-2336, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313321

RESUMO

It has been reported that genistein could improve metabolic syndromes. Our study aimed to investigate the effects and potential mechanisms of genistein on improving cholesterol metabolism in HepG2 cell. HepG2 cells were cultured with 0, 0.01, 1.00, 10.00, and 50.00 µM genistein for 24 hr. The current results showed a dose-dependent manner between genistein and intracellular contents of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and cellular apolipoprotein A1 (Apo-A1) secretion. TC was increased by 25.69%, meanwhile HDL-C and Apo-A1 were decreased by 56.00% and 25.93%, respectively, when the dosage of genistein was 1.00 µM. Genistein dose-dependently upregulated the protein and mRNA levels of sterol regulatory element binding proteins-2 (SREBP-2), as well as the mRNA levels of low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), by 145.91%, 72.29%, 310.23%, and 123.08%, respectively, when we gave 1.00 µM genistein, indicating that intracellular cholesterol synthesis and absorption of exogenous cholesterol were increased. In addition, the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and liver X receptor (LXRα), lowered by 58.23% and 34.86% at 0.01 µM genistein, were reduced in a dose-dependent manner. LXRα and ATP-binding cassette transporter A1 (ABCA1) protein levels were significantly (P < 0.05) decreased by 50.35% and 11.60% at 1.00 µM genistein, which indicated that cellular cholesterol efflux was inhibited. Taken together, our results suggested that genistein at dosage of more than 1.00 µM was able to increase the intracellular cholesterol levels by up regulating SREBP-2/LDLR/HMGCR pathway and suppressing PPARγ/LXRα/ABCA1 pathway. PRACTICAL APPLICATION: In this study, genistein appeared to be effective in reducing plasma cholesterol levels due to increase the intracellular cholesterol levels by upregulating cholesterol absorption through SREBP-2/LDLR/HMGCR pathway, and also downregulating cholesterol efflux via PPARγ/LXRα/ABCA1 pathway in vitro. In addition, plasma cholesterol is regarded as the key indicator of atherosclerosis; therefore, we believe that our findings could be used for further exploration on a possible therapeutic application of genistein for atherosclerosis.


Assuntos
Colesterol/metabolismo , Genisteína/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , HDL-Colesterol/genética , HDL-Colesterol/metabolismo , Expressão Gênica , Células Hep G2 , Humanos , Metabolismo dos Lipídeos , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
2.
Clin Biochem ; 73: 44-49, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31251897

RESUMO

BACKGROUND: Scavenger receptor class B type 1 (SR-BI) encoded by SCARB1 gene serves as a multifunctional HDL receptor, facilitating the uptake of cholesteryl esters from HDL to the liver. Recent studies have identified the association between the P376L missense mutation of the SCARB1 gene with increased serum HDL-Cholesterol level. However, the contribution of this variant to the development of cardiovascular disease (CVD) remains unclear. OBJECTIVE: We have investigated the association between the P376L polymorphism with the properties of HDL and CVD outcomes in a population sample recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: Six hundred and fifteen individuals who had a median follow-up period of 7 years were recruited as part of the MASHAD cohort. Anthropometric, biochemical parameters and HDL lipid peroxidation (HDLox) were assessed. Genotyping was performed using TaqMan-real-time-PCR based method. The association of P376L-rs74830766 with cardiovascular-risk-factors and CVD events were evaluated. RESULTS: Carriers of the P376L variant were significantly more likely than non-carriers to develop CVD using multivariate analyses adjusted for traditional CVD risk factors defined as: age, sex, BMI, presence of diabetes, or hypertension, positive smoking habit, and total cholesterol (OR: 3.75, 95%CI: 1.76-7.98, p = 0.001). In an adjusted model, there was a two fold increase in cardiovascular endpoints among individuals who were heterozygous for the P376L variant (hazard ratio, 2.08; 95% CI, 1.12-to 3.84, p = 0.02). Although there was no association between the presence of the P376L variant and HDL-C level, serum HDLox, measured as dysfunctional HDL, was 13% higher among carriers of the P376L variant than non-carriers. CONCLUSION: We have found that carriers of the P376L variant possessed higher HDLox and were at increased risk of CVD in a representative population-based cohort, as compared to non-carriers.


Assuntos
Doenças Cardiovasculares , HDL-Colesterol/metabolismo , Polimorfismo Genético , Receptores Depuradores Classe B/genética , Adulto , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , HDL-Colesterol/genética , Feminino , Seguimentos , Humanos , Peroxidação de Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Fatores de Risco , Receptores Depuradores Classe B/metabolismo
3.
Food Chem Toxicol ; 131: 110558, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31175915

RESUMO

Effects of Spirulina platensis 55% ethanol extract (SPL55) on lipid metabolism in high-fat diet-induced hyperlipidaemic rats were investigated. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry indicated that SPL55 was enriched with polyunsaturated fatty acids. Meanwhile, serum and liver lipid levels, including total triglyceride, total cholesterol, and low-density-lipoprotein cholesterol, were significantly decreased in hyperlipidaemic rats of SPL55. Analysis of tissue sections showed that SPL55 treatment could markedly inhibit hepatic lipid accumulation and steatosis. Moreover, SPL55 regulated the mRNA and protein expression levels of SREBP-1c, HMG-CoA, PEPCK, ACC, and AMPK genes involved in lipid metabolism. Furthermore, SPL55 led to decrease the abundances of Turicibacter, Clostridium_XlVa, and Romboutsia, which were positive correlation with lipid metabolism indicators, and has also enriched Alloprevotella, Prevotella, Porphyromonadaceae, and Barnesiella. These results provided evidence that SPL55 might be developed as a functional food to ameliorate lipid metabolic disorders and hyperlipidaemia.


Assuntos
Ácidos Graxos Insaturados/farmacologia , Fígado Gorduroso/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Spirulina/química , Animais , Peso Corporal/efeitos dos fármacos , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Dieta Hiperlipídica , Ácidos Graxos Insaturados/metabolismo , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/patologia , Microalgas/química , Ratos , Ratos Wistar , Triglicerídeos/sangue , Triglicerídeos/metabolismo
4.
Mar Drugs ; 17(5)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067674

RESUMO

Low-fat diets, lipid-modifying nutraceuticals and a higher level of physical activity are often recommended to reduce dyslipidemia. A double-blind, randomized, crossover, controlled trial was designed to evaluate the independent and synergistic effects of Arthrospira (Spirulina) maxima supplementation (4.5 g·day-1) with or without performing a physical exercise program (PEP: aerobic exercise (3 days·week-1) + high-intensity interval training (2 days·week-1)) on blood lipids and BMI of 52 sedentary men with excess body weight. During six weeks, all participants were assigned to four intervention treatments (Spirulina maxima with PEP (SE), placebo with PEP (Ex), Spirulina maxima without PEP (Sm), placebo without PEP (C; control)) and plasma lipids were evaluated spectrophotometrically pre- vs. post intervention in stratified subgroups (overweight, obese and dyslipidemic subjects). Pre/post comparisons showed significant reductions in all plasma lipids in the SE group, particularly in those with dyslipidemia (p ≤ 0.043). Comparing the final vs. the initial values, BMI, total cholesterol, triglycerides and low-density lipoprotein cholesterol were decreased. High-density lipoprotein cholesterol increased in all treatment groups compared to C. Changes were observed mostly in SE interventions, particularly in dyslipidemic subjects (p < 0.05). Spirulina maxima supplementation enhances the hypolipidemic effect of a systematic PEP in men with excess body weight and dyslipidemia.


Assuntos
Dislipidemias/tratamento farmacológico , Exercício , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Spirulina , Adulto , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Colesterol/metabolismo , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Estudos Cross-Over , Dieta , Suplementos Nutricionais , Método Duplo-Cego , Dislipidemias/sangue , Humanos , Lipídeos/sangue , Masculino , Obesidade/sangue , Sobrepeso/sangue , Triglicerídeos/sangue , Triglicerídeos/metabolismo
5.
Int J Mol Sci ; 20(4)2019 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-30813431

RESUMO

Lipoproteins containing apolipoprotein B modify associations of elevated urinary albumin excretion (UAE) with cardiovascular disease (CVD). Additionally, it is known that elevated UAE alters high-density lipoprotein functionality. Accordingly, we examined whether HDL features might also modify UAE-associated CVD. Multivariable Cox proportional-hazards modeling was performed on participants of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study at the baseline screening with standard lipid/lipoprotein analyses and, three-to-four years later (second screen), with nuclear magnetic resonance lipoprotein analyses focusing on HDL parameters including HDL particle (HDL-P) and apolipoprotein A-I concentrations. These were used with UAE and derived measures of HDL apoA-I content (apoA-I/HDL-C and apoA-I/HDL-P) in risk models adjusted for gender, age, apoB, diabetes, past CVD history, CRP and GFR. Interaction analysis was also performed. Baseline screening revealed significant associations inverse for HDL-C and apoA-I and direct for apoA-I/HDL-C. The second screening demonstrated associations inverse for HDL-P, large HDL-P, medium HDL-P, HDL size, and apoA-I/HDL-P. Significant interactions with UAE included apoA-I/HDL-C at the baseline screening, and apoA-I/HDL-P and medium HDL-P but not apoA-I/HDL-C at the second screening. We conclude that features of HDL particles including apoA-I/HDL-P, indicative of HDL apoA-I content, and medium HDL-P modify associations of elevated UAE with CVD risk.


Assuntos
Albuminúria/metabolismo , Doenças Cardiovasculares/metabolismo , HDL-Colesterol/metabolismo , Adulto , Idoso , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Apolipoproteína A-I/metabolismo , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/diagnóstico , Comorbidade , Feminino , Taxa de Filtração Glomerular , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Resultado do Tratamento
6.
Nutrients ; 11(3)2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30823398

RESUMO

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary in order to improve lipid HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7797 participants comprising 3559 men and 4238 women aged between 30 to 70 years were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories-no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). The multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with a higher HDL-C (ß =1.3154; p <0.0001 and ß = 6.5954; p = 0.0027, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.


Assuntos
HDL-Colesterol/metabolismo , Exercício/fisiologia , Esportes com Raquete , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan
7.
J Pak Med Assoc ; 69(3): 294-300, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30890817

RESUMO

OBJECTIVE: To evaluate the effect of motivational interviewing on diabetics related to perceived self-management and metabolic variables. METHODS: The randomised controlled and experimental study was conducted at a public hospital located in the city of Gaziantep in Turkey and comprised diabetes patients attending the outpatient clinic of endocrinology and metabolic diseases from April to July 2015. The subjects were randomised into two equal intervention and control groups. Four motivational interviewing sessions, each of which took about 15-20 minutes, were conducted by a nurse to the intervention group. Data was collected using a questionnaire and the Perceived Diabetes Self-Management Scale. RESULTS: Of the 60 subjects, there were 30 (50%) in ach of the two groups. The perceived self-management perception mean score of the intervention group was 17.1 } 5.6 at baseline and increased to 35.0 } 4.1 postintervention (p<0.05). Mean scores of body mass index, fasting and postprandial blood glucose, glycated haemoglobin, cholesterol, triglyceride, low density lipoprotein cholesterol and systolic and diastolic blood pressures of subjects in the intervention group decreased after the intervention, and their high density lipoprotein cholesterol mean scores increased (p<0.05). CONCLUSIONS: Motivational interviewing technique positively affected the metabolic control indicators of the diabetes patients and increased their perceived self-management.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Entrevista Motivacional/métodos , Autogestão/métodos , Adulto , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Jejum , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Triglicerídeos/metabolismo , Turquia
8.
J Pak Med Assoc ; 69(3): 306-312, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30890819

RESUMO

OBJECTIVE: To explore cardiovascular risk factors in people with newly-diagnosed type 2 diabetes mellitus. METHODS: The cross-sectional, prospective, multicentre, study was conducted from June 2014 till July 2015 at family practice clinics in 27 cities across Pakistan, and comprised individuals aged 30-50 years diagnosed with type 2 diabetes mellitus within the preceding six months. Laboratory investigations were conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and Aga Khan University Hospital, Karachi. The 10-year absolute risk of fatal or non-fatal coronary heart disease and stroke was calculated using the United Kingdom Prospective Diabetes Study Risk Engine version 2.0. Data were analysed using SPSS 19. RESULTS: Out of 888 subjects, 362(40.8%) were women and 526(59.2%) were men. The overall mean presenting age was 42.4}5.8 years. After stratification by age, those ≥40 years were significantly associated with higher glycated haemoglobin (p=0.02) and those ≤39 years were associated with higher levels of very low density lipoprotein (p=0.001) and triglyceride (p=0.006). The mean risk estimate for CHD was 9.7% (95% Confidence Interval (CI) 9.0- 10.1)), for fatal CHD 4.4% (95% CI 4.0-4.6), for stroke 1.5% (95% CI 1.2-1.7), and for fatal stroke 0.25% (95% CI 0.24- 0.26). CONCLUSIONS: There is a need for screening cardiovascular risk factors even in younger age groups of newlydiagnosed diabetes.


Assuntos
Doença das Coronárias/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Acidente Vascular Cerebral/epidemiologia , Adulto , Fatores Etários , Glicemia/metabolismo , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Estudos Transversais , Medicina de Família e Comunidade , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Lipoproteínas VLDL/metabolismo , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/metabolismo
9.
J Pak Med Assoc ; 69(3): 330-336, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30890823

RESUMO

OBJECTIVE: To estimate the adequacy of nutrients intake among females with metabolic syndrome. METHODS: The quantitative case-control study was conducted in November 2015 at King Fahd University Hospital, Al Khobar, Eastern Province, Saudi Arabia, and comprised patients who had three or more risk factors associated with metabolic syndrome. Group I had patients who met three of the six criteria components, Group II had those who met four components, and Group III had those who met more than four components. Healthy subjects were enrolled as controls. Socioeconomic data, as well as weight, height, body mass index and waist circumference, were collected. The 24-hour recall method was used for collecting data about food intake, and the nutrient intake was calculated by Saudi food composition tables. Data related to nutrient intake was compared with standard dietary requirements. RESULTS: Of the 216 subjects, 134(%) were patients and 82(%) were controlled. Among the patients, 20(15%) were in Group I, 34(25%) in Group II and 89(60%) were in Group III. None of the cases in the three groups had normal weight compared to 20(24.4%) controls (p<0.001). Intake of calories, protein and carbohydrates in groups II and III were lower than the controls and those in group I (p<0.05). Percentage of energy yielded from protein, fat, and carbohydrates by the patients differed significantly from normal values (p<0.05).. CONCLUSIONS: Majority of the patients failed to fulfill their requirements from essential nutrients. The higher the number of metabolic syndrome risk factors, the higher was the insufficiency of nutrient intake..


Assuntos
Dieta , Carboidratos da Dieta , Gorduras na Dieta , Proteínas na Dieta , Síndrome Metabólica/metabolismo , Adulto , Glicemia/metabolismo , Estudos de Casos e Controles , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade Mórbida/metabolismo , Sobrepeso/metabolismo , Arábia Saudita , Triglicerídeos/metabolismo
10.
Int J Mol Sci ; 20(3)2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30744100

RESUMO

BACKGROUND: We determined relationships of cholesterol efflux capacity (CEC), plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) with anti-c-terminus apoA-1 (Ac-terAA1) and anti-apolipoprotein (apo)-1 (AAA1) autoantibodies in subjects with and without Type 2 diabetes mellitus (T2D). METHODS: In 75 T2D subjects and 75 nondiabetic subjects, Ac-terAA1 and AAA1 plasma levels were measured by enzyme-linked immunosorbent assay. CEC was measured as [³H]-cholesterol efflux from human cultured fibroblasts to diluted individual subject plasma. Plasma EST and CET were assayed by isotope methods. RESULTS: Ac-terAA1 and AAA1 levels and were similar between T2D and control subjects. Univariate regression analysis (n = 150) demonstrated that Ac-terAA1 levels were inversely correlated with CEC, EST, CET, total cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B, (p < 0.05 to p < 0.01), but not with glucose and HbA1c. In separate multivariable linear regression models, CEC, EST and CET were inversely associated with Ac-terAA1 levels independently of age, sex, T2D and drug use (ß = -0.186, p = 0.026; ß = -0.261, p < 0.001; and ß = -0.321, p < 0.001; respectively). These associations were lost after additional adjustment for non-HDL cholesterol and triglycerides. No associations were observed for AAA1. CONCLUSIONS: CEC, plasma EST and CET are inversely associated with Ac-terAA1 autoantibodies, conceivably attributable to an inverse relationship of these autoantibodies with apolipoprotein B-containing lipoproteins.


Assuntos
Anticorpos Monoclonais/farmacologia , Apolipoproteína A-I/antagonistas & inibidores , HDL-Colesterol/metabolismo , Colesterol/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , Apolipoproteína A-I/química , Transporte Biológico , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino
11.
Food Funct ; 10(1): 448-457, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30628614

RESUMO

Momordica charantia (M. charantia) has been widely used to treat obesity due to its bioactive ingredients. This research aimed to investigate the anti-obesity effect of polysaccharides (FP) from fermented M. charantia with Lactobacillus plantarum NCU116 on high-fat induced obese rats. We found that FP could effectively lower the body weight gain, Lee's index, insulin resistance and cell sizes of epididymal adipose tissues in obese rats compared with polysaccharides from non-fermented M. charantia (NFP). FP treatments decreased the total cholesterol, triacylglycerols, and low-density lipoprotein cholesterol, leptin, whereas they elevated the high-density lipoprotein cholesterol, adiponectin, significantly in the serum of obese rats. Furthermore, administrations of FP notably improved oxidative balance in obese rats. Lipidomics results indicated that 24 potential biomarkers have been identified in serum. Additionally, 21 lipids were considerably altered by FP and NFP intakes, such as fatty acyls, glycerolipids, sphingolipids, sterol lipids and glycerophospholipids. The anti-obesity properties of FP were revealed via relieving insulin resistance and fat accumulation of obese rats, which was associated with the regulation of lipid metabolism. Overall, FP exerted more favourable impacts on the anti-obesity effect than NFP, which may be attributed to fermentation.


Assuntos
Lactobacillus plantarum/metabolismo , Momordica charantia/química , Momordica charantia/microbiologia , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fermentação , Humanos , Resistência à Insulina , Masculino , Momordica charantia/metabolismo , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/metabolismo , Polissacarídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
12.
PLoS One ; 14(1): e0209575, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30673715

RESUMO

OBJECTIVE: Previous studies have evaluated the link between metabolic syndrome and obesity with impaired lung function, however findings have been controversial. We aimed to compare lung function among subjects with different metabolic health and obesity status. METHODS: Total 10,071 participants were evaluated at the Health Promotion Center in Seoul St. Mary's Hospital between January 2012 and December 2014. Being metabolically healthy was defined as having fewer than three of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and abdominal obesity. Obesity status was defined as body mass index (BMI) higher than 25 kg/m2. Analyses of pulmonary function were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically health obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO). RESULTS: Metabolically unhealthy subjects were more prone to decreased lung function compared with their metabolically healthy counterparts, regardless of obesity status. When multinomial logistic regression analysis was performed according to quartiles of forced vital capacity (FVC) or forced expiratory volume in 1 second (FEV1) (% pred), after adjusting for age, sex, and smoking status, odds ratio (OR) for the lowest FVC and FEV1 (% pred) quartiles were significantly higher in MUHO subjects (1.788 [95% CI, 1.531-2.089] and 1.603 [95% CI, 1.367-1.881]) and lower in MHO subjects (0.768 [95% CI, 0.654-0.902] and 0.826 [95% CI, 0.700-0.976]) with MHNO group as the reference, when OR for highest FVC and FEV1 quartiles were considered as 1.0. CONCLUSION: Metabolic health is more closely associated with impaired lung function than obesity.


Assuntos
Pulmão/metabolismo , Obesidade Metabolicamente Benigna/metabolismo , Obesidade/metabolismo , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Jejum/sangue , Feminino , Humanos , Hiperglicemia , Hipertensão/complicações , Resistência à Insulina , Masculino , Síndrome Metabólica/complicações , Metabolismo/fisiologia , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Obesidade Metabolicamente Benigna/fisiopatologia , Razão de Chances , República da Coreia , Testes de Função Respiratória/métodos , Fatores de Risco , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Capacidade Vital
13.
Drug Metab Dispos ; 47(3): 227-233, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30567880

RESUMO

Anacetrapib is an inhibitor of cholesteryl ester transfer protein (CETP), associated with reduction in LDL cholesterol and increase in HDL cholesterol in hypercholesterolemic patients. Anacetrapib was not taken forward into filing/registration as a new drug for coronary artery diease, despite the observation of a ∼9% reduction in cardiovascular risk in a large phase III cardiovascular outcomes trial (REVEAL). Anacetrapib displayed no adverse effects throughout extensive preclinical safety evaluation, and no major safety signals were observed in clinical trials studying anacetrapib, including REVEAL. However, anacetrapib demonstrated a long terminal half-life in all species, thought to be due, in part, to distribution into adipose tissue. We sought to understand the dependence of anacetrapib's long half-life on adipose tissue and to explore potential mechanisms that might contribute to the phenomenon. In mice, anacetrapib localized primarily to the lipid droplet of adipocytes in white adipose tissue; in vitro, anacetrapib entry into cultured human adipocytes depended on the presence of a mature adipocyte and lipid droplet but did not require active transport. In vivo, the entry of anacetrapib into adipose tissue did not require lipase activity, as the distribution of anacetrapib into adipose was-not affected by systemic lipase inhibition using poloaxamer-407, a systemic lipase inhibitor. The data from these studies support the notion that the entry of anacetrapib into adipose tissue/lipid droplets does not require active transport, nor does it require mobilization or entry of fat into adipose via lipolysis.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Gotículas Lipídicas/metabolismo , Oxazolidinonas/farmacologia , Adipócitos/citologia , Tecido Adiposo/citologia , Animais , Linhagem Celular , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Meia-Vida , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Lipase/antagonistas & inibidores , Lipase/metabolismo , Lipólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxazolidinonas/administração & dosagem , Oxazolidinonas/uso terapêutico , Poloxâmero/farmacologia , Distribuição Tecidual/efeitos dos fármacos
14.
Int J Biol Macromol ; 125: 445-452, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30537499

RESUMO

The aim of this study is to investigate hypolipidemic and antioxidant effects of Pine needle polysaccharide (PNP) from Pinus massoniana in high-fat diet (HFD)-induced mice. PNP could significantly improve the serum lipid levels (total cholesterol, triacylglycerols, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), enhance the antioxidant enzymes levels (total antioxidant capability, superoxide dismutase, glutathione peroxidase, catalase), and decrease malondialdehyde (MDA) content in HFD-induced mice. PNP exhibited distinct antioxidant ability on the superoxide anions, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) in vitro. The average molecular weight (Mw) of PNP was 6.17 × 105 Da, and mainly of fucose, arabinose, galactose, glucose, galacturonic acid. These results suggested that PNP might be used as functional foods and natural drugs in enhancing antioxidant ability and alleviating the hyperlipidemia.


Assuntos
Antioxidantes/farmacologia , Hipolipemiantes/farmacologia , Pinus/química , Polissacarídeos/farmacologia , Animais , Compostos de Bifenilo/farmacologia , Catalase/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Glutationa Peroxidase/metabolismo , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Superóxido Dismutase/metabolismo , Triglicerídeos/metabolismo
15.
Ann Agric Environ Med ; 25(4): 635-641, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30586977

RESUMO

INTRODUCTION: Dietary pattern analysis is used to describe the dietary habits of a selected population. In many studies, dietary patterns (DPs) have been associated with risk factors for cardiovascular disease (CVD). The aim of the study was to assess the association between dietary patterns identified in the population of Lower Silesia, Poland, with anthropometric and biochemical risk factors for CVD. MATERIAL AND METHODS: The study group included 2,025 participants of the Prospective Urban Rural Epidemiological (PURE) Study. Dietary intake was evaluated based on data from the Food Frequency Questionnaire (FFQ). Dietary patterns were derived using principal component analysis (PCA). The relationship between DPs and body mass index (BMI), waist circumference, waist-hip ratio, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and fasting glucose level, was assessed. RESULTS: Three dietary patterns identified in the study explained 35.6% of total variance. The 'fruit, vegetables & dairy' DP, characterized by a high intake of vegetables, fruits, nuts, seeds, raisins, milk and low-fat dairy, was associated with improved lipid profile and anthropometric measures, lower diastolic blood pressure and lower fasting glucose concentration. 'Traditional' and 'fat & sugar' DPs were unfavourably associated with most of the risk factors for CVD presented in this study. CONCLUSIONS: Dietary patterns identified in this study were differently related to selected anthropometric and biochemical risk factors for CVD. 'Fruit, vegetables & dairy' DP was favourably associated with the biochemical and anthropometric CVD risk factors, and was characterized by higher nutritional value in comparison with 'traditional' and 'fat & sugar' DPs.


Assuntos
Doenças Cardiovasculares/psicologia , Comportamento Alimentar , Adulto , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dieta , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Estudos Prospectivos , Fatores de Risco , População Rural , Triglicerídeos/metabolismo
16.
Ann Agric Environ Med ; 25(3): 517-526, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30260180

RESUMO

INTRODUCTION AND OBJECTIVE: There are some clinical situations where a high level of HDL cholesterol (HDL-C) may be unfavourable. In these situations, HDL-C may undergo some changes, and even if its quantity is within the reference range, its quality is no longer the same. BRIEF DESCRIPTION OF STATE OF KNOWLEDGE: Diabetes is the state of elevated oxidative stress. Studies conducted to-date have revealed an increased production of the reactive forms of oxygen as the result of tissue damage in diabetes patients. The expression 'dysfunctional HDL' has been coined in the literature to describe high-density lipoproteins that lose their antioxidative and anti-inflammatory properties, that is, HDL-C that loses its basic functions. Recent observational studies have confirmed that the atheroprotective activity of properly functioning HDL-C is frequently impaired in clinical situations associated with oxidative stress. The presented review lays the foundation for a new approach to understanding how the functional properties of HDL help reduce cardiovascular risk. CONCLUSIONS: In the light of presented findings it seems that there is a need to seek a better diagnostic marker than HDL-C level. This study presents some possible directions for future research to bring us closer to the full understanding of the HDL particle and its role in patients with ischemic heart disease and type 2 diabetes.


Assuntos
Doenças Cardiovasculares/metabolismo , HDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Animais , Humanos , Estresse Oxidativo
17.
Lipids Health Dis ; 17(1): 200, 2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-30144814

RESUMO

BACKGROUND: Scavenger receptor BI (SR-BI) is a classic high-density lipoprotein (HDL) receptor, which mediates selective lipid uptake from HDL cholesterol esters (HDL-C). Apolipoprotein M (ApoM), as a component of HDL particles, could influence preß-HDL formation and cholesterol efflux. The aim of this study was to determine whether SR-BI deficiency influenced the expression of ApoM. METHODS: Blood samples and liver tissues were collected from SR-BI gene knockout mice, and serum lipid parameters, including total cholesterol (TC), triglyceride (TG), high and low-density lipoprotein cholesterol (HDL-C and LDL-C) and ApoM were measured. Hepatic ApoM and ApoAI mRNA levels were also determined. In addition, BLT-1, an inhibitor of SR-BI, was added to HepG2 cells cultured with cholesterol and HDL, under serum or serum-free conditions. The mRNA and protein expression levels of ApoM were detected by RT-PCR and western blot. RESULTS: We found that increased serum ApoM protein levels corresponded with high hepatic ApoM mRNA levels in both male and female SR-BI-/- mice. Besides, serum TC and HDL-C were also significantly increased. Treatment of HepG2 hepatoma cells with SR-BI specific inhibitor, BLT-1, could up-regulate ApoM expression in serum-containing medium but not in serum-free medium, even in the presence of HDL-C and cholesterol. CONCLUSIONS: Results suggested that SR-BI deficiency promoted ApoM expression, but the increased ApoM might be independent from HDL-mediated cholesterol uptake in hepatocytes.


Assuntos
Apolipoproteínas M/metabolismo , HDL-Colesterol/metabolismo , Hepatócitos/metabolismo , Receptores Depuradores Classe B/metabolismo , Animais , Apolipoproteínas M/sangue , Apolipoproteínas M/genética , HDL-Colesterol/sangue , Ciclopentanos/farmacologia , Feminino , Genótipo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tiossemicarbazonas/farmacologia
18.
Int J Mol Sci ; 19(7)2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29986413

RESUMO

High-density lipoprotein (HDL) particles have experienced a turbulent decade of falling from grace with widespread demotion from the most-sought-after therapeutic target to reverse cardiovascular disease (CVD), to mere biomarker status. HDL is slowly emerging from these dark times due to the HDL flux hypothesis wherein measures of HDL cholesterol efflux capacity (CEC) are better predictors of reduced CVD risk than static HDL-cholesterol (HDL-C) levels. HDL particles are emulsions of metabolites, lipids, protein, and microRNA (miR) built on the backbone of Apolipoprotein A1 (ApoA1) that are growing in their complexity due to the higher sensitivity of the respective “omic” technologies. Our understanding of particle composition has increased dramatically within this era and has exposed how our understanding of these particles to date has been oversimplified. Elucidation of the HDL proteome coupled with the identification of specific miRs on HDL have highlighted the “hormonal” characteristics of HDL in that it carries and delivers messages systemically. HDL can dock to most peripheral cells via its receptors, including SR-B1, ABCA1, and ABCG1, which may be a critical step for facilitating HDL-to-cell communication. The composition of HDL particles is, in turn, altered in numerous disease states including diabetes, auto-immune disease, and CVD. The consequence of changes in composition, however, on subsequent biological activities of HDL is currently poorly understood and this is an important avenue for the field to explore in the future. Improving HDL particle quality as opposed to HDL quantity may, in turn, prove a more beneficial investment to reduce CVD risk.


Assuntos
Doenças Cardiovasculares/metabolismo , HDL-Colesterol/metabolismo , Inflamação/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Apolipoproteína A-I/fisiologia , Biomarcadores , HDL-Colesterol/química , Humanos , Metaboloma , MicroRNAs , Modelos Animais , Proteoma , Fatores de Risco
19.
Kidney Blood Press Res ; 43(3): 970-978, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29913451

RESUMO

BACKGROUND/AIMS: Hypertriglyceridaemia (HTG) and reduction and dysfunction of high density lipoprotein (HDL) are common lipid disturbances in chronic kidney disease (CKD). HTG in CKD is caused mainly by the decreased efficiency of lipoprotein lipase (LPL)-mediated very low density lipoprotein triglyceride (VLDL-TG) lipolysis. It has not been clarified whether HDL dysfunction in CKD contributes directly to HTG development; thus, the aim of this study was to assess the impact of CKD progression on the ability of HDL to enhance LPL-mediated VLDL-TG lipolysis efficiency. METHODS: VLDL was isolated from non-dialysis patients in CKD stages 3 and 4 and from non-CKD patients. The VLDL was incubated with LPL at the constant LPL:VLDL-TG ratio, in the absence or presence of HDL. After incubation, the VLDL was separated and the percentage (%) of hydrolyzed TG was calculated. RESULTS: HDL presence increased the lipolysis efficiency of VLDL isolated from CKD and non-CKD patients, for the VLDL-TG> 50 mg/dl. Its effect was dependent on the VLDL-TG and HDL-cholesterol concentrations in the reaction mixtures: the higher the concentrations of VLDL-TG and HDL-cholesterol, the greater the effect. The positive impact of HDL on VLDL lipolysis was modified by CKD progression: the percentage of lipolyzed VLDL-TG in the presence of HDL decreased with a reduction in eGFR (r=0.43, p=0.009), and for patients with stage 4 CKD, no positive impact of HDL on lipolysis was observed. The percentage of lipolyzed TG correlated negatively with apoE and apoCs content in VLDL, and positively with HDL-apoCII, as well as with VLDL and HDL apoCII/ apoCIII ratios. The progression of CKD was associated with unfavourable changes in VLDL and HDL composition; apoE and apoCs levels increased in VLDL with a decrease in eGFR whereas the HDL-cholesterol level decreased. CONCLUSION: The progression of CKD affects lipoprotein composition and properties, and modulates the positive impact of HDL on VLDL lipolysis efficiency. In CKD patients, HDL deficiency and dysfunction can directly affect hypertriglyceridaemia development.


Assuntos
Hipertrigliceridemia/etiologia , Lipólise/efeitos dos fármacos , Lipase Lipoproteica/metabolismo , Lipoproteínas HDL/farmacologia , Lipoproteínas VLDL/metabolismo , Insuficiência Renal Crônica/patologia , Triglicerídeos/metabolismo , Idoso , HDL-Colesterol/metabolismo , Progressão da Doença , Feminino , Humanos , Lipoproteínas HDL/deficiência , Masculino , Pessoa de Meia-Idade
20.
Int J Mol Sci ; 19(6)2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29874886

RESUMO

Almost 600 million people are predicted to have diabetes mellitus (DM) by 2035. Diabetic patients suffer from increased rates of microvascular and macrovascular complications, associated with dyslipidaemia, impaired angiogenic responses to ischaemia, accelerated atherosclerosis, and inflammation. Despite recent treatment advances, many diabetic patients remain refractory to current approaches, highlighting the need for alternative agents. There is emerging evidence that high-density lipoproteins (HDL) are able to rescue diabetes-related vascular complications through diverse mechanisms. Such protective functions of HDL, however, can be rendered dysfunctional within the pathological milieu of DM, triggering the development of vascular complications. HDL-modifying therapies remain controversial as many have had limited benefits on cardiovascular risk, although more recent trials are showing promise. This review will discuss the latest data from epidemiological, clinical, and pre-clinical studies demonstrating various roles for HDL in diabetes and its vascular complications that have the potential to facilitate its successful translation.


Assuntos
Aterosclerose/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Lipoproteínas HDL/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , HDL-Colesterol/metabolismo , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/uso terapêutico , Fatores de Risco
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