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1.
PLoS One ; 15(8): e0238388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866186

RESUMO

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels. OBJECTIVE: To measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT. METHODS: Among 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS. RESULTS: The prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl-L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05). CONCLUSIONS: Although NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS.


Assuntos
Alanina Transaminase/metabolismo , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Aspartato Aminotransferases/metabolismo , Índice de Massa Corporal , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ácido Úrico/metabolismo , gama-Glutamiltransferase/metabolismo
2.
Am J Med ; 133(10): 1126-1134, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32569590

RESUMO

Cardiovascular disease remains one of the most prevalent and preventable chronic conditions worldwide. Diet modification is the foundation of cardiovascular disease prevention. Several dietary approaches have emerged to promote better cardiovascular health. The rapid dissemination of anecdotal and observational data through the internet and social media has caused confusion amongst providers and patients. The aim of this comprehensive review is to present objective insights into 2 of today's most popular fad diets: ketogenic diet and intermittent fasting. We will evaluate the performance of these diets based on their impact on cardiovascular risk factors.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Cetogênica/métodos , Dislipidemias/metabolismo , Jejum , Fibrilação Atrial , Glicemia/metabolismo , Pressão Sanguínea , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/prevenção & controle , Dietas da Moda , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos , Obesidade/metabolismo , Comportamento de Redução do Risco , Triglicerídeos/metabolismo , Perda de Peso
3.
Am J Clin Nutr ; 112(2): 373-380, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32511694

RESUMO

BACKGROUND: Evidence suggests low-grade inflammation as the cause of metabolic syndrome and suggests diet as a promoter of chronic inflammation. OBJECTIVE: We evaluated the association between inflammatory diets and the development of metabolic syndrome in Mexican adults. METHODS: A total of 399 participants of the Health Workers Cohort Study were included in this study. The follow-up period was 13 y. Metabolic syndrome definition was the presence of ≥3 of the following components: waist circumference ≥102 cm for males or ≥88 cm for females, blood pressure ≥130 mmHg for systolic or ≥85 mmHg for diastolic, HDL cholesterol <40 mg/dL for males and <50 mg/dL for females; triglycerides ≥150 mg/dL, and glucose ≥100 mg/dL. To evaluate the inflammatory potential of the diet we used the Dietary Inflammatory Index (DII), which was divided into quartiles. To assess the risk of metabolic syndrome we estimated HRs and 95% CIs using Cox proportional hazards models. RESULTS: After adjustment for potential confounders, we found a positive association between participants in the highest quartile (Q) of DII and the incidence of metabolic syndrome (HRQ4vsQ1 = 1.99; 95% CI: 1.03, 3.85; P-trend = 0.04) over a period of 13 y. When we divided the metabolic syndrome by its components, we found that participants in the highest quartile of DII were associated with hypertriglyceridemia (HRQ4vsQ1 = 2.28; 95% CI: 1.13, 4.57; P-trend = 0.01), hypertension (HRQ4vsQ1 = 2.22; 95% CI: 1.03, 4.77; P-trend = 0.032), and abdominal obesity (HRQ4vsQ1 = 2.68; 95% CI: 1.06, 6.79; P-trend = 0.02). CONCLUSIONS: A highly inflammatory diet is associated with metabolic syndrome, hypertension, abdominal obesity, and hypertriglyceridemia. Further studies are needed to corroborate the role of inflammation and diet in the development of metabolic syndrome; yet, a reduction in dietary components that have been linked to inflammation is desirable.


Assuntos
Dieta/efeitos adversos , Síndrome Metabólica/etnologia , Síndrome Metabólica/imunologia , Adulto , Glicemia/metabolismo , Pressão Sanguínea , HDL-Colesterol/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/fisiopatologia , Americanos Mexicanos , Pessoa de Meia-Idade , Triglicerídeos/metabolismo
4.
Lipids Health Dis ; 19(1): 56, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228618

RESUMO

BACKGROUND: Overconditioned dairy cows are prone to greater insulin resistance in transition to successfully adapt to negative energy balance. The associations among body condition score (BCS), insulin resistance, lipid metabolism and oxidative stress in cows during late lactation with positive energy balance remain to be elucidated. METHODS: The objectives of this study were to investigate insulin sensitivity and oxidative status in late lactating dairy cows with different BCS but similar milk production, parity and days in milk. Forty-two multiparous Holstein cows were fed the same diet under the same management and divided into three groups based on BCS: low BCS (LBCS; BCS ≤ 2.75; n = 12), medium BCS (MBCS; 3.0 ≤ BCS ≤ 3.5; n = 15) or high BCS (HBCS; BCS ≥ 3.75; n = 15). Blood samples used for analysis of biochemical and hematological parameters were collected from the coccygeal vein at the end of experiment. RESULTS: The concentrations of insulin and nonesterified fatty acid were higher and the revised quantitative insulin sensitivity check index (RQUICKI) was lower in HBCS cows than in LBCS and MBCS cows. These results suggest that insulin resistance exacerbates lipolysis in HBCS cows. Serum concentrations of very low-density lipoprotein, apolipoprotein A-I, and apolipoprotein B were lower in HBCS cows than in LBCS or MBCS cows. Although LBCS and MBCS cows had higher reactive oxygen species levels than did HBCS cows, the malondialdehyde concentration was not different among cows with different BCS. Ceruloplasmin activity was higher in MBCS and HBCS cows than in LBCS cows, but superoxide dismutase, glutathione peroxidase, and paraoxonase activities were not different among cows with different BCS. Despite the higher percentage of granulocytes in MBCS cows than in HBCS cows, no differences were found in leukocyte counts, red blood cell profiles and platelet profiles among the cows in the three groups. CONCLUSIONS: Results of this study showed that compared with MBCS and LBCS cows, HBCS cows at late lactation stage may have accumulated more hepatic triacylglycerol and lower antioxidant potential due to greater insulin resistance.


Assuntos
Resistência à Insulina/fisiologia , Lactação/metabolismo , Animais , Bovinos , HDL-Colesterol/metabolismo , Feminino , Resistência à Insulina/genética , Lactação/genética , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Monócitos/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Gravidez
5.
Am J Physiol Endocrinol Metab ; 318(6): E839-E847, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32286882

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise (n = 15), or conventional lifestyle advice (n = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8-32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; P < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6-36.1% to 8.9% (4.4-17.8%); P = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.


Assuntos
Apolipoproteína A-I/metabolismo , HDL-Colesterol/metabolismo , Exercício Físico , Gordura Intra-Abdominal/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Triglicerídeos/metabolismo , Adulto , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Cinética , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/terapia , Resultado do Tratamento , Perda de Peso
6.
Lipids Health Dis ; 19(1): 49, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32178676

RESUMO

BACKGROUND: Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDL-cholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis. METHODS: Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay. RESULTS: Concentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls. Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls. CONCLUSION: Our results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03052595 Registered on Feb 14, 2017.


Assuntos
Inflamação/imunologia , Inflamação/metabolismo , Lipoproteínas HDL/metabolismo , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Adulto , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Inflamação/sangue , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-17/sangue , Interleucina-17/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Interleucina-2/sangue , Interleucina-2/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Interleucina-7/sangue , Interleucina-7/metabolismo , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue
7.
Am J Clin Nutr ; 111(4): 779-786, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32140704

RESUMO

BACKGROUND: Observational studies have linked low vitamin D status to unfavorable cardiometabolic risk markers, but double-blinded vitamin D intervention studies in children are scarce. OBJECTIVES: The aim was to evaluate the effect of different doses of a vitamin D supplement on cardiometabolic risk markers in young healthy Swedish children with fair and dark skin. METHODS: Cardiometabolic risk markers were analyzed as secondary outcomes of a double-blind, randomized, milk-based vitamin D intervention trial conducted during late fall and winter in 2 areas of Sweden (latitude 63°N and 55°N, respectively) in both fair- and dark-skinned 5- to 7-y-old children. During the 3-mo intervention, 206 children were randomly assigned to a daily milk-based vitamin D3 supplement of either 10 or 25 µg or placebo (2 µg; only at 55°N). Anthropometric measures, blood pressure, serum 25-hydroxyvitamin D [25(OH)D], total cholesterol, HDL cholesterol, apoA-I, apoB, and C-reactive protein (CRP) were analyzed and non-HDL cholesterol calculated at baseline and after the intervention. RESULTS: At baseline, serum 25(OH)D was negatively associated with systolic and diastolic blood pressure (ß = -0.194; 95% CI: -0.153, -0.013; and ß = -0.187; 95% CI: -0.150, -0.011, respectively). At follow-up, there was no statistically significant difference in any of the cardiometabolic markers between groups. CONCLUSIONS: We could not confirm any effect of vitamin D supplementation on serum lipids, blood pressure, or CRP in healthy 5- to 7-y-old children. The study was registered at clinicaltrials.gov (NCT01741324).


Assuntos
Vitamina D/análogos & derivados , Biomarcadores/sangue , Pressão Sanguínea , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , HDL-Colesterol/metabolismo , Suplementos Nutricionais/análise , Método Duplo-Cego , Feminino , Coração/efeitos dos fármacos , Coração/fisiologia , Humanos , Masculino , Suécia , Vitamina D/administração & dosagem , Vitamina D/sangue
8.
Yakugaku Zasshi ; 140(2): 153-157, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32009037

RESUMO

Atherosclerosis is a vascular disease responsible for acute heart attacks and stroke, which are leading causes of death not only in industrialized countries but also worldwide, and the number of patients afflicted by this disease has been increasing in Japan. High-density lipoprotein (HDL) is the plasma lipoprotein that carries what is often called your "good cholesterol" through the blood. This good cholesterol moniker is associated with HDL because higher circulating levels of this lipoprotein are associated with a well-known reduction in the risk of arteriosclerosis. Moreover, many protective mechanisms by which HDL could reduce atherosclerosis are described, including reverse cholesterol transport, along with anti-oxidant, anti-inflammatory and anti-thrombosis activities. However, HDL-modulating therapies to lower cardiovascular risk are not yet available. It has recently been proposed that apolipoprotein A-I (apoA-I) binding protein (AIBP) enhances HDL function by accelerating lipid release from cells and reducing associated inflammatory processes. In this context, our research is focused on the function of HDL-related proteins, such as proteins that regulate HDL production (ATP-binding cassette transporters), and HDL-binding proteins. We expect that these studies could eventually help in the development of HDL-related prognostic and therapeutic strategies to reduce the burden of cardiovascular disease in the future.


Assuntos
Transportadores de Cassetes de Ligação de ATP/fisiologia , Aterosclerose , HDL-Colesterol/metabolismo , Desenvolvimento de Medicamentos , Apolipoproteína A-I/fisiologia , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Ligação Proteica
9.
Am J Physiol Gastrointest Liver Physiol ; 318(4): G725-G735, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068443

RESUMO

Recently, peripheral lymphatic vessels were found to transport high-density lipoprotein (HDL) from interstitial tissues to the blood circulation during reverse cholesterol transport. This function is thought to be critical to the clearance of cholesterol from atherosclerotic plaques. The role of organ-specific lymphatics in modulating HDL transport and composition is, however, incompletely understood. This study aimed to 1) determine the contribution of the lymphatics draining the intestine and liver (which are major sites of HDL synthesis) to total (thoracic) lymph HDL transport and 2) verify whether the HDLs in lymph are derived from specific organs and are modified during trafficking in lymph. The mesenteric, hepatic, or thoracic lymph duct was cannulated in nonfasted Sprague-Dawley rats, and lymph was collected over 5 h under anesthesia. Whole lymph and specific lymph lipoproteins (isolated by ultracentrifugation) were analyzed for protein and lipid composition. The majority of thoracic lymph fluid, protein, and lipid mass was sourced from the mesenteric, and to a lesser extent, hepatic lymph. Mesenteric and thoracic lymph were both rich in chylomicrons and very low-density lipoprotein, whereas hepatic lymph and plasma were HDL-rich. The protein and lipid mass in thoracic lymph HDL was mostly sourced from mesenteric lymph, whereas the cholesterol mass was equally sourced from mesenteric and hepatic lymph. HDLs were compositionally distinct across the lymph sources and plasma. The composition of HDL also appeared to be modified during passage from the mesenteric and hepatic to the thoracic lymph duct. Overall, this study demonstrates that the lipoproteins in lymph are organ specific in composition, and the intestine and liver appear to be the main source of HDL in the lymph.NEW & NOTEWORTHY High-density lipoprotein in lymph are organ-specific in composition and derive mostly from the intestine and liver. High-density lipoprotein also appears to be remodeled during transport through the lymphatics. These findings have implications to cardiometabolic diseases that involve perturbations in lipoprotein distribution and metabolism.


Assuntos
HDL-Colesterol/química , HDL-Colesterol/metabolismo , Sistema Linfático/anatomia & histologia , Sistema Linfático/fisiologia , Animais , Transporte Biológico , Feminino , Lipídeos/química , Fígado , Linfa/química , Mesentério , Proteínas/química , Ratos , Ratos Sprague-Dawley , Tórax
10.
Annu Rev Med ; 71: 191-201, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31986087

RESUMO

The development of potent cholesterol-reducing medications in the last decade of the twentieth century has altered the approach to prevention and treatment of cardiovascular disease (CVD). Initial experience with statins, and more recently with the addition of PCSK9 inhibitors, has proven that human CVD, like that in animal models, can be halted and regressed. Available clinical data show that the lower the achieved level of low-density lipoprotein cholesterol, the greater the regression of disease. Investigative studies are now aimed to understand those factors that both accelerate and impede this healing process. Some of these are likely to be modifiable, and the future of atherosclerotic CVD treatment is likely to be early screening, use of measures to repair atherosclerotic arteries, and prevention of most CVD events.


Assuntos
Aterosclerose/metabolismo , Placa Aterosclerótica/metabolismo , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Quilomícrons/metabolismo , Angiografia por Tomografia Computadorizada , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Macrófagos/metabolismo , Imagem por Ressonância Magnética , Camundongos , Camundongos Knockout , Camundongos Knockout para ApoE , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/prevenção & controle , Pró-Proteína Convertase 9/antagonistas & inibidores , Coelhos , Ratos , Receptores de LDL/genética , Receptores de LDL/metabolismo , Indução de Remissão , Triglicerídeos/metabolismo , Ultrassonografia de Intervenção
11.
Metabolism ; 104: 154141, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31923386

RESUMO

Functional assessment of cholesterol efflux capacity (CEC) to high-density lipoprotein (HDL) is an emerging tool for evaluating morbidity and mortality associated with cardiovascular disease (CVD). By promoting macrophage reverse cholesterol transport (RCT), HDL-mediated CEC is believed to play an important role in atherosclerotic lesion progression in the vessel wall. Furthermore, recent evidence indicates that the typical inverse associations between various forms of CEC and CV events may be strongly modulated by environmental systemic factors and traditional CV risk factors, in addition to autoimmune diseases. These factors influence the complex and dynamic composition of HDL particles, which in turn positively or negatively affect HDL-CEC. Herein, we review recent findings connecting HDL-CEC to traditional CV risk factors and cardiometabolic conditions (non-autoimmune diseases) as well as autoimmune diseases, with a specific focus on how these factors may influence the associations between HDL-CEC and CVD risk.


Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , HDL-Colesterol/metabolismo , Lipoproteínas HDL/metabolismo , Animais , Doenças Autoimunes/complicações , Doenças Cardiovasculares/complicações , Humanos , Fatores de Risco
12.
J Med Chem ; 63(4): 1660-1670, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-31990537

RESUMO

Endothelial lipase (EL) hydrolyzes phospholipids in high-density lipoprotein (HDL) resulting in reduction in plasma HDL levels. Studies with murine transgenic, KO, or loss-of-function variants strongly suggest that inhibition of EL will lead to sustained plasma high-density lipoprotein cholesterol (HDL-C) increase and, potentially, a reduced cardiovascular disease (CVD) risk. Herein, we describe the discovery of a series of oxadiazole ketones, which upon optimization, led to the identification of compound 12. Compound 12 was evaluated in a mouse pharmacodynamics (PD) model and demonstrated a 56% increase in plasma HDL-C. In a mouse reverse cholesterol transport study, compound 12 stimulated cholesterol efflux by 53% demonstrating HDL-C functionality.


Assuntos
HDL-Colesterol/metabolismo , Inibidores Enzimáticos/farmacologia , Cetonas/farmacologia , Lipase/antagonistas & inibidores , Oxidiazóis/farmacologia , Animais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacocinética , Cetonas/síntese química , Cetonas/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/farmacocinética , Relação Estrutura-Atividade
13.
Adipocyte ; 9(1): 51-56, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31996075

RESUMO

FTO gene polymorphisms are associated with obesity and food intake. This study aimed to investigate the association of FTO rs9939609 polymorphism genotypes with serum glucose, lipid profile and serum hormones level. This cross-sectional study was carried out on 196 randomly selected overweight adults. Anthropometric measurements including weight, height, body mass index (BMI), fat mass, and fat-free mass were assessed. Serum TGs, total cholesterol, HDL cholesterol, LDL cholesterol, glucose and insulin levels were measured. The FTO gene was Genotyped for rs9939609 polymorphism. Dietary intake was assessed by avalid 168-item semi-quantitative food frequency questionnaire (FFQ). The homozygotes for the FTO rs9939609 risk allele (A) had higher serum leptin (p = 0.005, F: 5.131) and lower HDL (p = 0.001, F: 7.687) level than TT genotype. The differences between TT and AT genotypes were not significant. The association remained significant for HDL level after adjustments for age and sex, calorie intake, physical activity, and BMI. The association between rs9939609 polymorphism genotypes and leptin was disappeared after adjustments for calorie intake and physical activity. In conclusion, rs9939609 risk allele was associated with higher serum leptin and lower HDL levels in overweight people. Further studies are warranted.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Predisposição Genética para Doença , Sobrepeso/sangue , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Adiponectina/sangue , Adiponectina/metabolismo , Adulto , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Estudos Transversais , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Insulina/sangue , Insulina/metabolismo , Leptina/sangue , Leptina/metabolismo , Masculino , Inquéritos Nutricionais , Sobrepeso/metabolismo , Adulto Jovem
14.
Arthritis Rheumatol ; 72(1): 20-30, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350818

RESUMO

Systemic lupus erythematosus (SLE) patients exhibit accelerated development of atherosclerosis and increased incidents of cardiovascular disease (CVD) that cannot be explained by traditional risk factors alone. Accumulating evidence suggests that reduced levels of high-density lipoproteins (HDLs), along with altered HDL composition and function, may contribute to the accelerated atherosclerosis in SLE patients. Normally, HDLs play various atheroprotective roles through facilitating cholesterol efflux, inhibiting vascular inflammation, and scavenging oxidative species. However, systemic inflammation, oxidative stress, and autoimmunity in SLE patients induce changes in HDL size distribution and proteomic and lipidomic signatures. These compositional changes in HDLs result in the formation of proinflammatory, dysfunctional HDL. These lupus-altered HDLs have impaired antiatherogenic function with reduced cholesterol efflux capacities, impaired antioxidation abilities, and diminished antiinflammatory properties. In fact, dysfunctional HDL may promote atherogenesis by inducing inflammation. Thus, dysfunctional HDLs could be an important biomarker of accelerated atherosclerosis in lupus. Additionally, HDL-targeted therapies, especially infusion of reconstituted HDLs, may serve as a potential therapeutic intervention for SLE patients with CVD.


Assuntos
Aterosclerose/metabolismo , Dislipidemias/metabolismo , Lipoproteínas HDL/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Aterosclerose/epidemiologia , Aterosclerose/imunologia , Colesterol/metabolismo , HDL-Colesterol/metabolismo , Dislipidemias/epidemiologia , Dislipidemias/imunologia , Humanos , Inflamação/imunologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Estresse Oxidativo/imunologia
15.
Int J Vitam Nutr Res ; 90(1-2): 95-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30932777

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious global health problem, thus the prevention and management of the disease is necessary. This study aimed to determine the effects of Ramadan Fasting (RF) on liver function, Visceral Adiposity Index (VAI) and Atherogenic Index of Plasma (AIP) in these patients. METHODS: Eighty-three NAFLD patients (57 males and 26 females) were enrolled in the study, 42 patients who practiced RF, between Jun 18 through July 17, 2015 and 41 patients in non-fasting groups. Anthropometric parameters and Ultrasound grading were measured before and after Ramadan. The biochemical parameters including lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides), liver enzymes (Aspartate aminotransferase, SGOT and Alanine aminotransferase, SGPT) were evaluated before and after Ramadan. AIP and VAI were calculated based on formula. RESULTS: The mean decreases in anthropometric indices were significantly different between groups. Similarly, the mean decrease in the total cholesterol values in the fasting group was remarkably greater than in the control group (p = 0.02). The values of AIP and VAI decreased at the end of the study in both group and the mean of changes showed no differences between groups (p = 0.79 and p = 0.65 for AIP and VAI, respectively). The changes in the concentrations of liver enzymes, as well as the severity of hepatic steatosis, showed remarkable differences between groups (p = 0.03, p = 0.05, and p = 0.02 for SGOT and SGPT, and Liver steatosis, respectively). CONCLUSION: RF improved liver steatosis in NAFLD patients and might be useful in the management of NAFLD.


Assuntos
HDL-Colesterol/metabolismo , Jejum/metabolismo , Hepatopatia Gordurosa não Alcoólica , Obesidade Abdominal , Triglicerídeos/metabolismo , HDL-Colesterol/química , Feminino , Humanos , Masculino , Triglicerídeos/química
16.
Artigo em Inglês | MEDLINE | ID: mdl-31678516

RESUMO

SR-B1 belongs to the class B scavenger receptor, or CD36 super family. SR-B1 and CD36 share an affinity for a wide array of ligands. Although they exhibit similar ligand binding specificity, SR-B1 and CD36 have some very specific lipid transport functions. Whereas SR-B1 primarily facilitates the selective delivery of cholesteryl esters (CEs) and cholesterol from HDL particles to the liver and non-placental steroidogenic tissues, as well as participating in cholesterol efflux from cells, CD36 primarily mediates the uptake of long-chain fatty acids in high fatty acid-requiring organs such as the heart, skeletal muscle and adipose tissue. However, CD36 also mediates cholesterol efflux and facilitates selective lipoprotein-CE delivery, although less efficiently than SR-B1. Interestingly, the ability or efficiency of SR-B1 to mediate fatty acid uptake has not been reported. In this paper, using overexpression and siRNA-mediated knockdown of SR-B1, we show that SR-B1 possesses the ability to facilitate fatty acid uptake. Moreover, this function is not blocked by BLT-1, a specific chemical inhibitor of HDL-CE uptake activity of SR-B1, nor by sulfo-N-succinimidyl oleate, which inhibits fatty acid uptake by CD36. Attenuated fatty acid uptake was also observed in primary adipocytes isolated from SR-B1 knockout mice. In conclusion, facilitation of fatty acid uptake is an additional function that is mediated by SR-B1.


Assuntos
Adipócitos/metabolismo , Ácidos Graxos/metabolismo , Receptores Depuradores Classe B/metabolismo , Adipócitos/efeitos dos fármacos , Animais , Antígenos CD36/antagonistas & inibidores , Antígenos CD36/genética , Antígenos CD36/metabolismo , Células Cultivadas , Ésteres do Colesterol/metabolismo , HDL-Colesterol/metabolismo , Ciclopentanos/farmacologia , Técnicas de Silenciamento de Genes , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Ácidos Oleicos/farmacologia , Cultura Primária de Células , RNA Interferente Pequeno/metabolismo , Receptores Depuradores Classe B/antagonistas & inibidores , Receptores Depuradores Classe B/genética , Succinimidas/farmacologia , Tiossemicarbazonas/farmacologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-31863971

RESUMO

Several hereditary point mutations in human apolipoprotein A-I (apoA-I) have been associated with low HDL-cholesterol levels and/or increased coronary artery disease (CAD) risk. However, one apoA-I mutation, the V19L, recently identified in Icelanders, has been associated with increased HDL-cholesterol levels and decreased CAD risk. In an effort to gain mechanistic insight linking the presence of this mutation in apoA-I with the increase of HDL-cholesterol levels we evaluated the effect of V19L mutation on the conformational integrity and functional properties of apoA-I in lipid-free and lipidated form. ApoA-I[V19L] was found to be thermodynamically destabilized in lipid-free form and displays an increased capacity to associate with phospholipids compared to WT apoA-I. When associated to reconstituted HDL (rHDL), apoA-I[V19L] was more thermodynamically stabilized than WT apoA-I. ApoA-I[V19L] displayed normal capacity to promote ABCA1-mediated cholesterol efflux and to activate the enzyme LCAT, in lipid-free and rHDL-associated forms, respectively. Additionally, rHDL-associated apoA-I[V19L] showed normal capacity to promote ABCG1-mediated cholesterol efflux, but 45% increased capacity to promote SR-BI-mediated cholesterol efflux, while the SR-BI-mediated HDL-lipid uptake was normal. Overall, our findings show that the apoA-I V19L mutation does not affect the first steps of HDL biogenesis pathway. However, the increased capacity of apoA-I[V19L] to associate with phospholipids, in combination with the enhanced thermodynamic stability of lipoprotein-associated apoA-I[V19L] and increased capacity of apoA-I[V19L]-containing lipoprotein particles to accept additional cholesterol by SR-BI could account for the increased HDL-cholesterol levels observed in human carriers of the mutation.


Assuntos
Apolipoproteína A-I/química , HDL-Colesterol/metabolismo , Mutação de Sentido Incorreto , Fosfolipídeos/metabolismo , Animais , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , Sítios de Ligação , Células HEK293 , Humanos , Camundongos , Simulação de Dinâmica Molecular , Ligação Proteica , Estabilidade Proteica
18.
Food Funct ; 11(1): 544-551, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31848551

RESUMO

Hyperlipidemia associated with cardiovascular health, and bone loss with regard to osteoporosis contribute to increased morbidity and mortality and are influenced by diet. Soy protein has been shown to reduce cholesterol levels, and its isoflavones may improve bone health. The objective of this study was to determine the effects of soy protein on lipid profiles and biomarkers of bone metabolism and inflammation. Ninety men and women (aged 27-87) were randomly assigned to consume 40 g of soy or casein protein daily for three months. Both soy and casein consumption significantly reduced bone alkaline phosphatase (P = 0.011) and body fat % (P < 0.001), tended to decrease tartrate-resistant acid phosphatase (P = 0.066), and significantly increased serum insulin-like growth factor-I (IGF-1) (P < 0.001), yet soy increased IGF-1 to a greater extent (P = 0.01) than casein. Neither treatment affected total cholesterol, HDL cholesterol, LDL cholesterol, or C-reactive protein. These results demonstrate that daily supplementation of soy and casein protein may have positive effects on indices of bone metabolism and body composition, with soy protein being more effective at increasing IGF-1, an anabolic factor, which may be due to soy isoflavones' role in upregulating Runx2 gene expression, while having little effect on lipid profiles and markers of inflammation.


Assuntos
Osso e Ossos/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Proteínas de Soja/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Densidade Óssea , Proteína C-Reativa/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Feminino , Humanos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Pak J Pharm Sci ; 32(5): 2099-2105, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31813876

RESUMO

Cardiovascular diseases and cancer are the leading cause of death worldwide, changed lifestyle and eating habits are the major contributing factors. Daily consumption cooking oils is one of the nutritional sources in today's life. Oils are available in market in the blend of two or more oils to get the maximum health benefits. There are number of factors which decide the pathogenic or protective effects of these oils, like fatty acids(FAs) composition, duration and extent of thermal exposure, daily intake and consumption duration. While processing the food cooking oils are thermally oxidized, that exert deleterious health effects, when taken for long time. The present study designed to evaluate the lipid peroxidation and level of oxidative stress in rabbits treated with repeatedly heated mix vegetable oils, in low (L-RHMVO) and high doses (H-RHMVO) in comparison with single time heated olive (STH-OO), canola (STH-CO), sunflower (STH-SO) oils individually and in mixture (STH-MVO) collected from Karachi (Pakistan).Six groups of animals treated with all these processed oils for 16 weeks along with normal diet .Control group was kept on normal rabbit diet. Animal body and organ weight was recorded. Blood samples were collected to measure plasma Malondialdehyde (MDA), Homocysteine(H-Cys), Creatine phosphokinase (CPK), Lactate dehydrogenase (LDH),C-reactive protein (CRP) and lipid profile (TGs, Total-cholesterol, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol).Statistically highly significant (p<0.005) increased body and organ weight along with Total-cholesterol, TGs, LDL-cholesterol, VDLD-Cholesterol, H-Cys, MDA,CPK,LDH & CRP and decreased HDL-cholesterol was found in H-RHMVO and L-RHMVO groups in dose dependent manner compared to control and single time heated oils groups. Among the single time heated oils STH-SO fed animals had significant (p<0.05) increase in lipid periodization and oxidative stress parameters. STH-OO showed least variation from control with significant increase in HDL-cholesterol level. The finding of this study not only confirms health deleterious effect of vegetable oils when used in thermally oxidized condition but also suggests induced-metabolic changes with oxidative stress. So more advance studies simulating real-life exposure to multiple hazardous substances is required.


Assuntos
Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Óleos Vegetais/administração & dosagem , Óleos Vegetais/química , Animais , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Ácidos Graxos/metabolismo , Temperatura Alta , Lipídeos/química , Masculino , Olea/química , Oxirredução/efeitos dos fármacos , Paquistão , Coelhos
20.
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
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