Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 639
Filtrar
1.
Life Sci ; 266: 118870, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310040

RESUMO

AIM: Betel-nut, a popular masticatory among Southeast Asian populations is a class I carcinogen, previously associated with dyslipidemia and aberrant lipid metabolism, and is reported to be used more frequently by females, than males. This study investigates the potential of repurposing the anti-diabetic drug, vildagliptin, a dipeptidyl peptidase-4 inhibitor, for alleviating the oncogenic condition in female Swiss Albino mice administered an aqueous extract of betel-nut (AEBN) orally (2 mg ml-1) for 24 weeks. MAIN METHODS: Tissues were investigated by histopathological, immunohistochemical and apoptosis assays. Biochemical analyses of oxidative stress markers and lipid profile were performed using different tissues and sera. The expressions of different proteins involved in lipid metabolism and oncogenic pathways were evaluated by Western blotting. KEY FINDINGS: AEBN induced carcinogenesis primarily in the liver by significantly impairing AMPK signaling, inducing oxidative stress, activating Akt/mTOR signaling, increasing Ki-67 immunoreactivity and cyclin D1 expression, and significantly diminishing apoptosis. Co-administration of AEBN with vildagliptin (10 mg kg-1 body weight) for 8 weeks reduced liver dysplasia, and significantly decreased free palmitic acid, increased free oleic acid, normalized lipid profile, decreased oxidative stress, cyclin D1 expression, Ki-67 immunoreactivity, and Bcl2 expression, and increased the ratio of apoptotic/non-apoptotic cells. Mechanistically, vildagliptin elicited these physiological and molecular alterations by restoring normal AMPK signaling and reducing the cellular expressions of FASN and HMGCR, restoring AMPK-dependent phosphorylation of p53 at Ser-15 and reducing Akt/mTOR signaling. SIGNIFICANCE: These results indicate that vildagliptin may alleviate betel-nut induced carcinogenesis in the liver of female mice.


Assuntos
Areca/toxicidade , Inibidores da Dipeptidil Peptidase IV/farmacologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/toxicidade , Vildagliptina/farmacologia , Animais , Carcinogênese , Dislipidemias/induzido quimicamente , Dislipidemias/patologia , Dislipidemias/prevenção & controle , Feminino , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Transdução de Sinais
2.
Ter Arkh ; 92(9): 94-101, 2020 Oct 14.
Artigo em Russo | MEDLINE | ID: mdl-33346437

RESUMO

The review presents an analysis of studies on the role of the intestinal microbiota and microbiome in lipid metabolism and the development of dyslipidemia, atherosclerosis and cardiovascular diseases. The role of the intestine as a metabolic organ with a multifactorial strain evolution, involved in lipid metabolism, cholesterol homeostasis and enterohepatic circulation is shown. The influence of microbial imbalance on the development of dyslipidemia and atherosclerosis is considered. Special attention is paid to preventive therapy with hypolipidemic probiotics. It is shown that the use of probiotics with hypolipidemic properties and consisting of a mixture of such strains asLactobacillus plantarumCECT7527, CET7528 and CECT7529, mixtures ofLactobacillus acidophilusLa-5,Bifidobacterium lactisBB-12,Bifidobacterium animalis lactisBB-12 contribute to reducing the level of LDL-C, CCS, TG, are safe and well tolerated, can be used as an adjuvant non-drug therapy in combination with hypolipidemic drugs for dyslipidemia, multifocal atherosclerosis.


Assuntos
Aterosclerose , Dislipidemias , Microbioma Gastrointestinal , Probióticos , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Dislipidemias/tratamento farmacológico , Dislipidemias/etiologia , Dislipidemias/prevenção & controle , Humanos , Fatores de Risco
3.
Ann Pediatr Endocrinol Metab ; 25(4): 199-207, Dec. 31, 2020.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1146623

RESUMO

The Committee on Dyslipidemia of Korean Pediatric and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for dyslipidemia in Korean children and adolescents. These guidelines were formulated with the Grading of Recommendations, which include both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines are based on the 2011 National Heart, Lung, and Blood Institute Guidelines, which focus on the prevention of cardiovascular disease in children and draw from a comprehensive review of evidence. These guidelines contain the definition of and screening process for dyslipidemia and introduce new dietary methods: the Cardiovascular Health Integrated Lifestyle Diet (CHILD)-1, the CHILD-2-low-density lipoprotein cholesterol, and the CHILD-2-triglyceride. Potential drug therapies for dyslipidemia along with their main effects and doses were also included.


Assuntos
Humanos , Criança , Adolescente , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco , Aterosclerose/prevenção & controle , Dislipidemias/prevenção & controle , Comportamento Alimentar , República da Coreia/epidemiologia , Estilo de Vida
4.
Nefrología (Madrid) ; 40(5): 499-505, sept.-oct. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-199030

RESUMO

El uso de fármacos inhibidores de la proprotein convertase subtilisin/kexin type 9 (iPCSK9) ha supuesto un cambio en el tratamiento de la dislipidemia en sus efectos sobre los eventos cardiovasculares. Actualmente, disponemos de 2principios activos comercializados (evolocumab y alirocumab) que tienen indicación en los pacientes que no alcanzan unos valores de lipoproteína de baja densidad (LDL) inferior a 100mg/dl habiendo presentado un evento cardiovascular previo y con dosis máximas o intolerancia a las estatinas. Los ensayos clínicos con iPCSK9 han incluido a pacientes con enfermedad renal, aunque con límites en el filtrado glomerular de hasta 20ml/min/1,73 m2 en el menos restrictivo de ellos. Los subanálisis de estos ensayos clínicos han demostrado eficacia en los pacientes con insuficiencia renal, tanto en la mejoría del perfil lipídico como en la reducción de eventos cardiovasculares. Derivado de su intenso efecto en la reducción de colesterol LDL han surgido algunas dudas sobre su seguridad que actualmente están resueltas y que confieren a los iPCSK9 un evidente beneficio cardiovascular también pacientes con enfermedad renal


The use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has changed the clinical practice of dyslipidemia and their effects in cardiovascular events. Nowadays 2active principles have been commercialized (evolocumab and alircumab) with indication in patients with low-density lipoprotein (LDL) cholesterol over 100mg/dl, history of cardiovascular events and higher statins doses prescribed. Clinical trials with PCSK9i have included chronic kidney disease (CKD) patients, although glomerular filtration rate has been limited up to 20ml/min/1,73m2 or higher. The published sub-analysis of them have demonstrated at least the same efficacy (in reduction of LDL and cardiovascular events) and safety in patients with CKD. However, as these drugs are very powerful in reducing LDL cholesterol, some safety concerns appeared in the past. Once safety is probed, we conclude that PCSK9i are beneficial for CKD patients


Assuntos
Humanos , Pró-Proteína Convertase 9/administração & dosagem , Pró-Proteína Convertase 9/antagonistas & inibidores , Dislipidemias/terapia , Segurança do Paciente , Resultado do Tratamento , Insuficiência Renal Crônica/terapia , Pró-Proteína Convertase 9/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Lipoproteínas LDL , Guias de Prática Clínica como Assunto/normas , Dislipidemias/prevenção & controle
5.
Clín. investig. arterioscler. (Ed. impr.) ; 32(5): 209-218, sept.-oct. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-196745

RESUMO

En general, las guías de práctica clínica tanto europeas con americanas han abordado el control de la dislipidemia aterogénica de forma poco convincente e incluso superficial, en gran medida por las limitaciones terapéuticas disponibles. En consecuencia, esta dislipidemia está infradiagnosticada, infratratada e infracontrolada. Dada la reciente aparición de la guía 2019 de la European Atherosclerosis Society y de la European Society of Cardiology sobre el control de las dislipidemias, parece oportuno examinar su posicionamiento con respecto a la dislipidemia aterogénica y/o sus principales componentes, el aumento en las lipoproteínas ricas en triglicéridos y la disminución del colesterol de las lipoproteínas de alta densidad


In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein cholesterol


Assuntos
Humanos , Dislipidemias/prevenção & controle , Guias de Prática Clínica como Assunto/normas , Doenças Cardiovasculares/prevenção & controle , Triglicerídeos/normas , HDL-Colesterol/análise , Lipoproteínas HDL/normas , Apolipoproteínas B/normas , Aterosclerose/prevenção & controle , Hipolipemiantes/uso terapêutico , Hipertrigliceridemia/tratamento farmacológico , Hipertrigliceridemia/genética
7.
s.l; Annals of Internal Medicine; 2020; Sept. 22, 2020.
Monografia em Inglês | BIGG - guias GRADE | ID: biblio-1127784

RESUMO

In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.


Assuntos
Humanos , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Dislipidemias/diagnóstico , Dislipidemias/prevenção & controle , Reabilitação Cardíaca , Prática Clínica Baseada em Evidências
9.
Metabolism ; 107: 154226, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32277945

RESUMO

BACKGROUND: Aberrant endothelial function is a major contributing factor in cardiovascular disease. Dyslipidemia leads to decreased nitric oxide (NO) bioavailability, an early sign of endothelial failure. Low insulin gene enhancer protein (ISL1) levels decrease healthy NO bioavailability. We hypothesized that the microRNA miR-652-3p negatively regulates endothelial ISL1 expression and that dyslipidemia-induced miR-652-3p upregulation induces aberrant endothelial functioning via ISL1 downregulation. METHODS: Various in vitro experiments were conducted in human umbilical vein endothelial cells (HUVECs). Luciferase assays were performed in HEK293 cells. We constructed a high-fat diet (HFD) Apoe-/- murine model of dyslipidemia and a rat model of low-density lipoprotein (LDL)-induced dyslipidemia to conduct in vivo and ex vivo experiments. RESULTS: Luciferase assays confirmed miR-652-3p's targeting of the ISL1 3'-untranslated region (3'-UTR). Simvastatin blocked oxidized LDL (ox-LDL)-induced increases in miR-652-3p and ox-LDL-induced decreases in ISL1 protein expression, endothelial NO synthase (eNOS) activation, and NO production. Simvastatin's effects were abrogated by miR-652-3p overexpression and phenocopied by miR-652-3p inhibition. The dyslipidemic mouse model exhibited increased miR-652-3p and decreased ISL1 protein levels in the endothelium, effects opposed by simvastatin or miR-652-3p inhibition. The impact of simvastatin in vivo was abolished by overexpressing miR-652-3p or knocking-down ISL1. The rat model of dyslipidemia exhibited a similar pattern of miR-652-3p upregulation, attenuated ISL1 protein levels, decreased eNOS activation, and decreased NO production, effects mitigated by simvastatin. CONCLUSIONS: Dyslipidemia upregulates endothelial miR-652-3p, which decreases ISL1 protein levels, eNOS activation, and NO production. Simvastatin therapy lowers endothelial miR-652-3p expression to protect endothelial function under dyslipidemic conditions.


Assuntos
Dislipidemias/patologia , Dislipidemias/prevenção & controle , Endotélio/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Proteínas com Homeodomínio LIM/biossíntese , MicroRNAs/biossíntese , Fatores de Transcrição/biossíntese , Animais , Apolipoproteínas E/genética , Regulação para Baixo/efeitos dos fármacos , Dislipidemias/genética , Ativação Enzimática , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/efeitos dos fármacos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Sprague-Dawley
10.
J Ovarian Res ; 13(1): 11, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005271

RESUMO

Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder and the most common gynecological endocrinopathy among reproductive-aged women. Current remedies are often used only to control its signs and symptoms, while they are not thoroughly able to prevent complications. Quercetin is an herbal bioactive flavonoid commonly used for the treatment of metabolic and inflammatory disorders. Thus, this systematic review was conducted to evaluate the efficacy of quercetin supplementation in subjects with PCOS. Databases until March 2019 were searched. All human clinical trials and animal models evaluating the effects of quercetin on PCOS women were included. Out of 253 articles identified in our search, 8 eligible articles (5 animal studies and 3 clinical trials) were reviewed. The majority of studies supported the beneficial effects of quercetin on the ovarian histomorphology, folliculogenesis, and luteinisation processes. The effects of quercetin on reducing the levels of testosterone, luteinizing hormone (LH), and insulin resistance were also reported. Although quercetin improved dyslipidemia, no significant effect was reported for weight loss. It is suggested that the benefits of quercetin may be more closely related to antioxidant and anti-inflammatory features of quercetin rather than weight-reducing effects. Therefore, this review article provides evidence that quercetin could be considered as a potential agent to attenuate PCOS complications. However, due to the paucity of high-quality clinical trials, further studies are needed.


Assuntos
Antioxidantes/uso terapêutico , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Quercetina/uso terapêutico , Adulto , Animais , Dislipidemias/metabolismo , Dislipidemias/prevenção & controle , Feminino , Humanos , Resistência à Insulina , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/metabolismo
11.
PLoS One ; 15(2): e0228932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32040532

RESUMO

Although the beneficial effects of probiotics in the prevention or treatment of metabolic disorders have been extensively researched, the precise mechanisms by which probiotics improve metabolic homeostasis are still not clear. Given that probiotics usually exert a comprehensive effect on multiple metabolic disorders, defining a concurrent mechanism underlying the multiple effects is critical to understand the function of probiotics. In this study, we identified the SIRT1-dependent or independent PGC-1α pathways in multiple organs that mediate the protective effects of a strain of Lactobacillus plantarum against high-fat diet-induced adiposity, glucose intolerance, and dyslipidemia. L. plantarum treatment significantly enhanced the expression of SIRT1, PPARα, and PGC-1α in the liver and adipose tissues under HFD-fed condition. L. plantarum treated mice also exhibited significantly increased expressions of genes involved in bile acid synthesis and reverse cholesterol transport in the liver, browning and thermogenesis of adipose tissue, and fatty acid oxidation in the liver and adipose tissue. Additionally, L. plantarum treatment significantly upregulated the expressions of adiponectin in adipose tissue, irisin in skeletal muscle and subcutaneous adipose tissue (SAT), and FGF21 in SAT. These beneficial changes were associated with a significantly improved HFD-induced alteration of gut microbiota. Our findings suggest that the PGC-1α-mediated pathway could be regarded as a potential target in the development of probiotics-based therapies for the prevention and treatment of metabolic disorders.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Doenças Metabólicas/prevenção & controle , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Probióticos/uso terapêutico , Tecido Adiposo/metabolismo , Adiposidade , Animais , Ácidos e Sais Biliares/biossíntese , Colesterol/metabolismo , Dislipidemias/metabolismo , Dislipidemias/prevenção & controle , Dislipidemias/terapia , Microbioma Gastrointestinal , Intolerância à Glucose/metabolismo , Intolerância à Glucose/prevenção & controle , Intolerância à Glucose/terapia , Lactobacillus plantarum/fisiologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Doenças Metabólicas/terapia , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Sirtuína 1/metabolismo
12.
Molecules ; 25(3)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32012786

RESUMO

Adropin is a unique hormone encoded by the energy homeostasis-associated (Enho) gene. Adropin is produced in the liver and brain, and also in peripheral tissues such as in the heart and gastrointestinal tract. Furthermore, adropin is present in the circulatory system. A decade after its discovery, there is evidence that adropin may contribute to body weight regulation, glucose and lipid homeostasis, and cardiovascular system functions. In this review, we summarize and discuss the physiological, metabolic, and pathophysiological factors regulating Enho as well as adropin. Furthermore, we review the literature addressing the role of adropin in adiposity and type 2 diabetes. Finally, we elaborate on the role of adropin in the context of the cardiovascular system, liver diseases, and cancer.


Assuntos
Adiposidade/efeitos dos fármacos , Dislipidemias/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Obesidade/tratamento farmacológico , Humanos
13.
Praxis (Bern 1994) ; 109(1): 31-34, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31910767

RESUMO

CoLaus: Diet, the Forgotten Key to Preventing Cardiovascular Diseases Abstract. Healthy eating is paramount for the prevention and management of cardiovascular diseases. Still, data from the CoLaus study show that dietary management of cardiovascular risk factors and cardiovascular disease is little implemented. Less than one fifth of participants with dyslipidemia reported being on a hypolipidemic diet, and only half of participants with diabetes reported being on an antidiabetic diet. Further, the occurrence of a myocardial infarction was not associated with an improvement in dietary quality.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Dieta , Dislipidemias , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/prevenção & controle , Dislipidemias/prevenção & controle , Humanos
14.
Sci Rep ; 10(1): 1245, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988303

RESUMO

Fenugreek (Trigonella foenum-graecum) is an annual herbaceous plant and a staple of traditional health remedies for metabolic conditions including high cholesterol and diabetes. While the mechanisms of the beneficial actions of fenugreek remain unknown, a role for intestinal microbiota in metabolic homeostasis is likely. To determine if fenugreek utilizes intestinal bacteria to offset the adverse effects of high fat diets, C57BL/6J mice were fed control/low fat (CD) or high fat (HFD) diets each supplemented with or without 2% (w/w) fenugreek for 16 weeks. The effects of fenugreek and HFD on gut microbiota were comprehensively mapped and then statistically assessed in relation to effects on metrics of body weight, hyperlipidemia, and glucose tolerance. 16S metagenomic analyses revealed robust and significant effects of fenugreek on gut microbiota, with alterations in both alpha and beta diversity as well as taxonomic redistribution under both CD and HFD conditions. As previously reported, fenugreek attenuated HFD-induced hyperlipidemia and stabilized glucose tolerance without affecting body weight. Finally, fenugreek specifically reversed the dysbiotic effects of HFD on numerous taxa in a manner tightly correlated with overall metabolic function. Collectively, these data reinforce the essential link between gut microbiota and metabolic syndrome and suggest that the preservation of healthy populations of gut microbiota participates in the beneficial properties of fenugreek in the context of modern Western-style diets.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Bactérias/genética , Glicemia , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Dislipidemias/prevenção & controle , Glucose/metabolismo , Intolerância à Glucose/prevenção & controle , Hiperlipidemias/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Extratos Vegetais/metabolismo , RNA Ribossômico 16S/genética , Trigonella/metabolismo
15.
Nutrients ; 12(2)2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31991567

RESUMO

Excessive triglyceride accumulation in lipid-metabolizing tissues is associated with an increased risk of a variety of metabolic diseases. Kamishoyosan (KSS) is a Kampo composed of 10 constituent herbs, and contains moutan cortex (MC) and paeonol (PN) as the major ingredient of MC. Here, we demonstrate the molecular mechanism underlying the effect of KSS on the differentiation of mouse preadipocytes (3T3-L1 cells). KSS inhibited the accumulation of triglycerides in a dose-dependent manner in 3T3-L1 cells that were induced to differentiate into adipocytes. We also found that MC and PN were responsible for the anti-adipogenetic effect of KSS and significantly suppressed the expression of CCAAT/enhancer-binding proteins-δ (C/EBP-δ) mRNA 3 days after the induction of differentiation. Thus, PN may contribute to the anti-adipogenetic property of MC in 3T3-L1 cells. In addition, PN inhibited dexamethasone (Dex)-induced glucocorticoid receptor (GR) promoter activity. Taken together, these results suggest that PN suppresses C/EBP-δ expression by inhibiting Dex-induced GR promoter activity at the early stage of differentiation and, consequently, delays differentiation into mature adipocytes. Our results suggest that the habitual intake of Kampo-containing PN contributes to the prevention of the onset of metabolic diseases by decreasing the excessive accumulation of triglycerides in lipid-metabolizing tissues.


Assuntos
Acetofenonas/farmacologia , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Dislipidemias/prevenção & controle , Hipolipemiantes/farmacologia , Receptores de Glucocorticoides/antagonistas & inibidores , Triglicerídeos/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Proteína delta de Ligação ao Facilitador CCAAT/genética , Proteína delta de Ligação ao Facilitador CCAAT/metabolismo , Dislipidemias/metabolismo , Dislipidemias/patologia , Camundongos , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Transdução de Sinais
16.
Nutrients ; 12(1)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968556

RESUMO

The pursuit of cholesterol lowering natural products with less side effects is needed for controlling dyslipidemia and reducing the increasing toll of cardiovascular diseases that are associated with morbidity and mortality worldwide. The present study aimed at the examining effects of p-methoxycinnamic acid diesters (PCO-C) from carnauba (Copernicia prunifera)-derived wax on cytotoxic, genotoxic responses in vitro and on dyslipidemia and liver oxidative stress in vivo, utilizing high-fat diet (HFD) chronically fed Swiss mice. In addition, we evaluated the effect of PCO-C on the expression of key cholesterol metabolism-related genes, as well as the structural interactions between PCO-C and lecithin-cholesterol acyl transferase (LCAT) in silico. Oral treatment with PCO-C was able to reduce total serum cholesterol and low-density lipoprotein (LDL) levels following HFD. In addition, PCO-C reduced excessive weight gain and lipid peroxidation, and increased the gene expression of LCAT following HFD. Furthermore, the high affinity of the studied compound (ΔG: -8.78 Kcal/mol) towards the active sites of mutant LCAT owing to hydrophobic and van der Waals interactions was confirmed using bioinformatics. PCO-C showed no evidence of renal and hepatic toxicity, unlike simvastatin, that elevated aspartate aminotransferase (AST) levels, a marker of liver dysfunction. Finally, PCO-C showed no cytotoxicity or genotoxicity towards human peripheral blood lymphocytes in vitro. Our results suggest that PCO-C exerts hypocholesterolemic effects. The safety of PCO-C in the toxicological tests performed and the reports of its beneficial biological effects render this a promising compound for the development of new cholesterol-lowering therapeutics to control dyslipidemia. More work is needed for further elucidating PCO-C role on lipid metabolism to support future clinical studies.


Assuntos
Antioxidantes/farmacologia , Cinamatos/farmacologia , Dieta Hiperlipídica , Dislipidemias/prevenção & controle , Hipolipemiantes/farmacologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/toxicidade , Biomarcadores/sangue , Células Cultivadas , Cinamatos/toxicidade , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/etiologia , Humanos , Hipolipemiantes/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Camundongos , Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo
17.
Nutrients ; 12(1)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968607

RESUMO

This study aimed to investigate the beneficial effects of seabuckthorn freeze-dried powder on high-fat diet-induced obesity and related lipid metabolism disorders, and further explored if this improvement is associated with gut microbiota. Results showed that seabuckthorn freeze-dried powder administration decreased body weight, Lee's index, adipose tissue weight, liver weight, and serum lipid levels. Moreover, treatment with seabuckthorn freeze-dried powder effectively reduced fat accumulation by modulating the relative expression of genes involved in lipid metabolism through down-regulation of encoding lipogenic and store genes, including SREBP-1c, PPAR-γ, ACC, and SCD1, and up-regulation of regulating genes of fatty acid oxidation, including HSL, CPT-1, and ACOX. Especially, seabuckthorn freeze-dried powder regulated the composition of gut microbiota, such as increasing the ratio of Firmicutes/Bacteroidetes, decreasing relative abundance of harmful bacteria (Desulfovibrio), and increasing relative abundance of beneficial bacteria (Akkermansia and Bacteroides). The changes of beneficial bacteria had a positive correlation with genes encoding lipolysis and a negative correlation with genes encoding lipid lipogenesis and store. The harmful bacteria were just the opposite. Besides, changes in gut microbiota had an obvious effect in the secretion of main metabolites-short-chain fatty acids (SCFAs), especially propionic acid. Thus, our results indicated that the seabuckthorn freeze-dried powder could ameliorate high-fat diet-induced obesity and obesity-associated lipid metabolism disorders by changing the composition and structure of gut microbiota.


Assuntos
Fármacos Antiobesidade/farmacologia , Dislipidemias/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Hippophae , Hipolipemiantes/farmacologia , Lipídeos/sangue , Obesidade/prevenção & controle , Extratos Vegetais/farmacologia , Ganho de Peso/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Animais , Fármacos Antiobesidade/isolamento & purificação , Biomarcadores/sangue , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/genética , Dislipidemias/microbiologia , Liofilização , Regulação da Expressão Gênica , Hippophae/química , Hipolipemiantes/isolamento & purificação , Masculino , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/genética , Obesidade/microbiologia , Extratos Vegetais/isolamento & purificação , Pós
18.
Nutr Metab Cardiovasc Dis ; 30(2): 190-200, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31757571

RESUMO

BACKGROUND AND AIM: Higher fish consumption has been reported to be associated with a lower incidence of coronary artery disease (CAD). We hypothesized that higher fish intake may be associated with lower serum level of non-high-density lipoprotein cholesterol (non-HDL-C) levels, representing the entire dyslipidemia spectrum, and a healthy lifestyle. METHODS AND RESULTS: This cross-sectional study was conducted in a population of 1270 apparently healthy males over the age of 50 years without lipid-modifying therapy at the Health Planning Center of Nihon University Hospital between April and August 2018. The average number of days of fish intake per week was 2.6 ± 1.4. We performed analysis of variance using fish consumption as a categorical variable (0-1 day, 2-3 days, 4-5 days, or 6-7 days per week). The serum non-HDL-C levels in the 6-7 days fish intake group were significantly lower than those in the 0-1 and 2-3days fish intake groups. Furthermore, with increasing frequency of fish intake per week, the proportion of subjects with cigarette smoking decreased (p = 0.026), that of subjects engaging in habitual aerobic exercises increased (p = 0.034), and the sleep duration of the subjects increased (p < 0.0001). CONCLUSIONS: These results suggest that a high frequency of fish intake, that is a fish intake of 6-7 days per week, was associated with healthier lifestyle behaviours as well as lower non-HDL-C levels, and thus may represent a component of a healthy lifestyle associated with a lower risk of CAD in Japanese males over the age of 50. CLINICAL TRIAL REGISTRATION: UMIN (http://www.umin.ac.jp/). STUDY ID: UMIN000035899.


Assuntos
Aterosclerose/prevenção & controle , Colesterol/sangue , Dieta Saudável , Dislipidemias/prevenção & controle , Peixes , Comportamentos Relacionados com a Saúde , Comportamento de Redução do Risco , Alimentos Marinhos , Fatores Etários , Idoso , Animais , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Exercício Físico , Voluntários Saudáveis , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes , Valor Nutritivo , Fatores de Proteção , Recomendações Nutricionais , Medição de Risco , Fatores de Risco , Fatores Sexuais , Sono , Fatores de Tempo
19.
J Clin Pathol ; 73(7): 384-390, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31757783

RESUMO

Monogenic dyslipidaemia is a diverse group of multisystem disorders. Patients may present to various specialities from early childhood to late in adult life, and it usually takes longer before the diagnosis is established. Increased awareness of these disorders among clinicians is imperative for early diagnosis. This best practice review provides an overview of primary dyslipidaemias, highlighting their clinical presentation, relevant biochemical and molecular tests. It also addresses the emerging role of genetics in the early diagnosis and prevention of these disorders.


Assuntos
Dislipidemias/diagnóstico , Doenças Metabólicas/diagnóstico , Algoritmos , Dislipidemias/genética , Dislipidemias/patologia , Dislipidemias/prevenção & controle , Diagnóstico Precoce , Humanos , Doenças Metabólicas/genética , Doenças Metabólicas/patologia , Doenças Metabólicas/prevenção & controle , Prognóstico
20.
Zhonghua Nei Ke Za Zhi ; 59(1): 18-22, 2020 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-31887831

RESUMO

The prevalence of dyslipidemia in Chinese adult is increasing dramatically, which poses a severe challenge to the prevention and treatment of atherosclerotic cardiovascular diseases. In recent years, a series of new research results have been published, providing a lot of new information for the management strategy of dyslipidemia. In order to apply these new research results to clinical practice for the further prevention and treatment of dyslipidemia more reasonably and effectively, the China Cholesterol Education Program (CCEP) Working Committee organized joint expert meeting and revised the "Expert Advice on Prevention and Treatment of Dyslipidemia in China Cholesterol Education Program 2014", in which a new classification standard for cardiovascular risk stratification has been proposed, and the target value of lipid-lowering therapy has been updated.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Dislipidemias , Guias de Prática Clínica como Assunto , Adulto , China , Dislipidemias/prevenção & controle , Dislipidemias/terapia , Humanos , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...