Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.757
Filtrar
1.
J Agric Food Chem ; 67(48): 13307-13317, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679333

RESUMO

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


Assuntos
Anticolesterolemiantes/metabolismo , Hipercolesterolemia/dietoterapia , Polissacarídeos Bacterianos/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
2.
J Agric Food Chem ; 67(43): 11922-11930, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31576748

RESUMO

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


Assuntos
Anticolesterolemiantes/administração & dosagem , Colesterol/metabolismo , Citrus/química , Microbioma Gastrointestinal , Hipercolesterolemia/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Pectinas/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Humanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
4.
J Agric Food Chem ; 67(38): 10614-10623, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483658

RESUMO

Type 2 diabetes (T2D) is a pandemic disease chiefly characterized by hyperglycemia. In this study, the combination of serum lipidomic and metabolomic approach was employed to investigate the effect of arabinoxylan on type 2 diabetic rats and identify the critical biomarkers of T2D. Metabolomics analysis revealed that branched-chain amino acids, 12α-hydroxylated bile acids, ketone bodies, and several short- and long-chain acylcarnitines were significantly increased in T2D, whereas lysophosphatidylcholines (LPCs) were significantly decreased. Lipidomics analysis indicated T2D-related dyslipidemia was mainly associated with the increased levels of acetylcarnitine, free fatty acids (FFA), diacylglycerols, triacylglycerols, and cholesteryl esters and the decreased levels of some unsaturated phosphatidylcholines (less than 22 carbons). These variations indicated the disturbed amino acid and lipid metabolism in T2D, and the accumulation of incompletely oxidized lipid species might eventually contribute to impaired insulin action and glucose homeostasis. Arabinoxylan treatment decreased the concentrations of 12α-hydroxylated bile acids, carnitines, and FFAs and increased the levels of LPCs. The improved bile acid and lipid metabolism by arabinoxylan might be involved in the alleviation of hypercholesterolemia and hyperlipidemia in T2D.


Assuntos
Anticolesterolemiantes/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Xilanos/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Carnitina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Metabolômica , Ratos
5.
Life Sci ; 233: 116702, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31356905

RESUMO

AIMS: We previously demonstrated that iron overload induces endothelial dysfunction and oxidative stress, which could increase the risk for atherosclerosis. However, the iron-related harmfulness under a genetic predisposition to atherosclerosis is still unclear. Here, we have tested the hypothesis that chronic iron overload may change vascular reactivity associated with worsening of the atherosclerotic process in apolipoprotein E knockout (apoE(-/-)) mice. MAIN METHODS: Serum and aortas of wild-type (WT) and apoE(-/-) mice injected with iron-dextran (IO, 10 mg/mouse/day, ip) or saline 5 times a week for 4 weeks, were used. KEY FINDINGS: Iron overload increased serum levels of iron and biomarkers of liver injury and oxidative stress, and iron deposition in the aorta in both lines, but only apoE(-/-) IO mice had intensified hypercholesterolemia and atherosclerosis. By scanning electron microscopy, the small endothelial structural damage caused by iron in WT was worsened in the apoE(-/-) group. However, endothelial dysfunction was found only in the apoE(-/-) IO group, identified by impaired relaxation to acetylcholine and hyperreactivity to phenylephrine associated with reduced nitric oxide modulation. Moreover, tiron and indomethacin attenuated reactivity to phenylephrine with greater magnitude in aortas of the apoE(-/-) IO group. Confirming, there were changes in the antioxidant (superoxide dismutase and catalase) activity, increased expression of cyclooxygenase-2 in the aorta and elevated levels of thromboxane A2 and prostacyclin metabolites in the urine of apoE(-/-) IO. SIGNIFICANCE: Our results showed that chronic iron overload intensifies the atherosclerotic process and induces endothelial dysfunction in atherosclerotic mice, probably due to the oxidative stress and the imbalance between the relaxing and contractile factors synthesized by the damaged endothelium.


Assuntos
Apolipoproteínas E/fisiologia , Aterosclerose/patologia , Endotélio Vascular/patologia , Hipercolesterolemia/patologia , Sobrecarga de Ferro/complicações , Estresse Oxidativo , Acetilcolina/metabolismo , Animais , Aterosclerose/etiologia , Aterosclerose/metabolismo , Endotélio Vascular/metabolismo , Feminino , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Ferro/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Óxido Nítrico/metabolismo
6.
J Oleo Sci ; 68(6): 517-524, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31168041

RESUMO

Abdominal fat accumulation causes metabolic syndrome, which is a cluster of metabolic abnormalities such as dyslipidemia, glucose intolerance, insulin resistance or hyperinsulinemia, and hypertension, leading to the development of diabetes and cardiovascular disease. Diets are known to contribute to the development or prevention of metabolic syndrome. Several studies have reported that the quality of dietary proteins may be an important modulator of the risk of this syndrome. We investigated the effects of consuming egg white protein (EWP) or lactic-fermented egg white (LE), an easy-to-consume form of egg white, on the development of metabolic syndrome in animal models and humans. In comparison with casein, dietary EWP decreased lymphatic lipid transport in thoracic lymph duct-cannulated rats. In an in vitro experiment, EWP pepsin hydrolysate decreased the cholesterol micellar solubility and cholesterol transfer rate from micelles to oil phase, and increased water-holding capacity, settling volume in water, and relative viscosity compared with casein pepsin hydrolysate. The daily consumption of LE for 8 weeks reduced serum total cholesterol and LDL cholesterol levels in men with mild hypercholesterolemia. Furthermore, dietary EWP reduced the body fat mass of rats by increasing the body protein mass and accelerating hepatic ß-oxidation. The daily consumption of LE for 12 weeks reduced the visceral fat area and improved the ratio of the visceral to subcutaneous fat area. Taken together, these results indicated that dietary EWP and LE would be useful for preventing or alleviating metabolic syndrome.


Assuntos
Dieta , Proteínas Dietéticas do Ovo/administração & dosagem , Proteínas Dietéticas do Ovo/farmacologia , Síndrome Metabólica/prevenção & controle , Síndrome Metabólica/terapia , Tecido Adiposo/metabolismo , Animais , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Modelos Animais de Doenças , Humanos , Hipercolesterolemia/metabolismo , Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Linfa/metabolismo , Síndrome Metabólica/etiologia , Micelas , Oxirredução , Pepsina A/farmacologia , Proteínas/metabolismo , Ratos , Solubilidade , Gordura Subcutânea/metabolismo , Ducto Torácico/metabolismo
7.
Blood Coagul Fibrinolysis ; 30(5): 205-216, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31157678

RESUMO

: The current study explores potential characteristic metabolic signatures associated with the high cholesterol (CHO), and the progression of coronary artery stenosis (CAS) in high-CHO patients. A metabolomics strategy based on ultra high-performance liquid chromatography/MS-MS and multivariate statistics has been implemented to identify potential biomarkers in high-CHO patients with different levels of CAS. The current study included 57 individuals, comprising 17 healthy paticipants, and 40 high-CHO patients. The high CHO patients were subgrouped based on the computed tomography angiography results, that is, CHO+ no ART (n = 10), CHO+ ART less than 50% (n = 13), CHO+ ART 50-75% (n = 11), and CHO+ ART more than 75% (n = 6). After metabolomics study, 16 discriminating metabolites in positive ion mode and 17 discriminating metabolites in negative ion mode were regarded as possible biomarker candidates to reflect metabolic traits differences between patients with healthy subjects and CHO. A total of six metabolites were tentatively identified as potential biomarkers for the progression diagnosis of CAS: three lysophosphatidylcholines (Lyso-phosphocholine, lysoPC and Lysopersicon esculentum, lysoPE), proline betaine and tryptophan, and prasterone sulfate. The results demonstrated that tryptophan and proline betaine could differentiate the patients with or without high CHO. Tryptophan, prasterone sulfate, LysoPE (0 : 0/18 : 2) or LysoPE (18 : 2/0 : 0), and LysoPE (0 : 0/18 : 1) or LysoPE (18 : 1/0 : 0) could differentiate the patients with severe stenosis (ART > 70%) from the healthy or mild stenosis ones. Proline betaine and significant decrease of LysoPC (17 : 0) could also be a promising biomarker for the mild stenosis (ART < 50%).


Assuntos
Estenose Coronária/sangue , Estenose Coronária/complicações , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Metaboloma , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estenose Coronária/metabolismo , Progressão da Doença , Feminino , Humanos , Hipercolesterolemia/metabolismo , Masculino , Metabolômica , Pessoa de Meia-Idade , Projetos Piloto
8.
Nat Commun ; 10(1): 2375, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147543

RESUMO

Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins and is involved in many physiological processes. Obesity, as a worldwide healthcare problem, has attracted more and more attention. To investigate the role of adipose HuR, we generate adipose-specific HuR knockout (HuRAKO) mice. As compared with control mice, HuRAKO mice show obesity when induced with a high-fat diet, along with insulin resistance, glucose intolerance, hypercholesterolemia and increased inflammation in adipose tissue. The obesity of HuRAKO mice is attributed to adipocyte hypertrophy in white adipose tissue due to decreased expression of adipose triglyceride lipase (ATGL). HuR positively regulates ATGL expression by promoting the mRNA stability and translation of ATGL. Consistently, the expression of HuR in adipose tissue is reduced in obese humans. This study suggests that adipose HuR may be a critical regulator of ATGL expression and lipolysis and thereby controls obesity and metabolic syndrome.


Assuntos
Tecido Adiposo Branco/metabolismo , Proteína Semelhante a ELAV 1/genética , Intolerância à Glucose/genética , Hipercolesterolemia/genética , Resistência à Insulina/genética , Lipase/genética , Obesidade/genética , Adipócitos/patologia , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/imunologia , Animais , Crescimento Celular , Dieta Hiperlipídica , Proteína Semelhante a ELAV 1/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Intolerância à Glucose/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Hipertrofia , Inflamação/imunologia , Lipase/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Biossíntese de Proteínas , Estabilidade de RNA/genética , Gordura Subcutânea/metabolismo
9.
J Orthop Surg Res ; 14(1): 172, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182124

RESUMO

BACKGROUND: Increased tendon pain and tendon damage is a significant complication related to hyperlipidemia. Unlike the well-established pathogenesis associated with increased serum concentrations of total cholesterol, triglycerides, and low-density lipoprotein in atherosclerotic cardiovascular disease, the role of hyperlipidemia in promoting tendon damage remains controversial and requires mechanistic clarity. METHODS: In this study, we analyzed the consequences of hypercholesterolemia on the integrity of the collagen-based architecture of the Achilles tendon. The Achilles tendons from rabbits fed with normal-cholesterol (nCH) and high-cholesterol (hCH) diets were analyzed. We studied the morphology of tendons, distribution of lipids within their collagen-rich milieu, the relative amounts of fibrillar collagen I and collagen III, and selected biomechanical parameters of the tendons at the macroscale and the nanoscale. RESULTS: Histological assays of hCH tendons and tenosynovium demonstrated hypercellular areas with increased numbers of macrophages infiltrating the tendon structure as compared to the nCH tendons. While Oil Red staining revealed lipid-rich deposits in the hCH tendons, hybridization of tendon tissue with the collagen hybridizing peptide (CHP) demonstrated damage to the collagen fibers. Fourier-transform infrared (FTIR) spectra showed the presence of distinct peaks consistent with the presence of cholesterol ester. Additionally, the hCH tendons displayed regions of poor collagen content that overlapped with lipid-rich regions. The hCH tendons had a substantial fourfold increase in the collage III to collagen I ratio as compared to the nCH tendons. Tendons from the hCH rabbits showed poor biomechanical characteristics in comparison with control. The biomechanical changes were evident at the macrolevel and the nanolevel of tendon structure. CONCLUSIONS: Our findings support the hypothesis that hypercholesterolemia coincides with the weakening of the tendons. It is likely that the intimate contact between collagen fibrils and cholesterol deposits contributes to the weakening of the fibrillar structure of the tendons.


Assuntos
Tendão do Calcâneo/metabolismo , Tendão do Calcâneo/patologia , Colesterol/metabolismo , Modelos Animais de Doenças , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Animais , Colágeno/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Hipercolesterolemia/etiologia , Coelhos
10.
Thromb Res ; 180: 74-85, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229924

RESUMO

BACKGROUND: The incretin hormone Glucagon-like peptide 1(GLP-1) plays a pivotal role in maintaining glucose homeostasis with effects also on the cardiovascular system. GLP-1 influences platelet functions by increasing the inhibitory action of nitric oxide (NO) and reducing oxidative stress. To date, the role of hypercholesterolemia (HyC) on platelet GLP-1 effects needs to be elucidated. METHODS: Forty-five subjects with primary HyC and twenty normocholesterolemic controls (NoC) were enrolled. In platelets from all subjects, the native GLP-1 (7-36), the truncated GLP-1 (9-36) and the GLP-1 analogue Liraglutide were evaluated in their ability to interfere with the activation of NO/PKG/VASP, PI-3K/Akt e MAPK/ERK-1/2 pathways and oxidative stress. Furthermore, in HyC subjects the role of a lipid-lowering therapy with statin on GLP-1 related peptide effects on platelet function was evaluated. RESULTS: Unlike in NoC, in platelets from HyC subjects the GLP-1 related peptides GLP-1 (7-36), GLP-1 (9-36) and Liraglutide all failed to: i) increase the antiaggregating effects of NO and the NO-induced VASP-ser239 phosphorylation, ii) decrease phosphorylation levels of Akt and ERK-2 and iii) reduce reactive oxygen species (ROS) generation. The treatment with simvastatin (40 mg/die) in HyC (n = 18) significantly reduced total and LDL cholesterol levels, platelet aggregability/activation, ROS production and NO action but did not modify platelet sensitivity to the GLP-1 effects. CONCLUSION: Collectively, these results indicate that hypercholesterolemia per se is characterized by a resistance to GLP-1 effects on platelets and this impairment is not corrected by treatment with simvastatin.


Assuntos
Plaquetas/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Sinvastatina/uso terapêutico , Adulto , Plaquetas/metabolismo , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
11.
Inflamm Res ; 68(7): 581-595, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31073849

RESUMO

OBJECTIVE: Hypercholesterolemia is associated with the development of a pro-inflammatory state and is a documented risk factor for progression to insulin resistance, nonalcoholic fatty liver and cardiovascular diseases. Sitagliptin is an incretin enhancer that improves glucose tolerance by inhibiting dipeptidyl peptidase-4, but it also has reported anti-inflammatory effects. The current study was thus undertaken to examine the interactions of dietary Cholesterol (Cho) and sitagliptin on markers of inflammation. METHODS: Male Sprague-Dawley rats were provided diets high in Cho and gavaged with vehicle or an aqueous suspension of sitagliptin (100 mg/kg/day) from day 10 through day 35. Molecular methods were used to analyze the lipid profile and inflammatory markers in liver and serum samples. H&E-stained liver sections were used for histopathological evaluation. Hepatic influx of mononuclear cells and necrosis were assessed by immunohistochemistry. RESULTS: Sitagliptin reduced triglyceride and Cho levels in serum of rats on the control diet but these effects were abrogated in rats on the high-Cho diet. Sitagliptin produced a significant increase in the expression of hepatic inflammatory markers (Tnfa, Il1b, and Mcp1) and a corresponding increase in serum TNFα and IL-1ß in rats on the high-Cho diet, but it had no effect on rats on the control diet. Additionally, sitagliptin had no effect on liver morphology in rats on the control diet, but it produced hepatic histopathological changes indicative of necrosis and mononuclear cell infiltration in rats on the high-Cho diet. These mononuclear cells were identified as macrophages and T cells. CONCLUSION: When provided in the context of a high-Cho diet, these findings reveal previously unrecognized hepato-inflammatory effects of sitagliptin that are accompanied by evidence of hepatic necrosis and mononuclear cell infiltration.


Assuntos
Colesterol na Dieta/farmacologia , Citocinas/metabolismo , Hipercolesterolemia/metabolismo , Incretinas/farmacologia , Fígado/efeitos dos fármacos , Fosfato de Sitagliptina/farmacologia , Animais , Hipercolesterolemia/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos Sprague-Dawley
12.
Am J Clin Nutr ; 109(5): 1239-1250, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31051508

RESUMO

BACKGROUND: Replacing dietary saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFA) reduces the plasma low-density lipoprotein (LDL) cholesterol and subsequently the risk of cardiovascular disease. However, beyond changes in LDL cholesterol, we lack a complete understanding of the physiologic alterations that occur when improving dietary fat quality. OBJECTIVES: The aim of this study was to gain knowledge of metabolic alterations paralleling improvements in the fat quality of the diet. METHODS: We recently conducted an 8-wk, double-blind, randomized controlled trial replacing SFAs with PUFAs in healthy subjects with moderate hypercholesterolemia (n = 99). In the present substudy, we performed comprehensive metabolic profiling with multiple platforms (both nuclear magnetic resonance- and mass spectrometry-based technology) (n = 99), and analyzed peripheral blood mononuclear cell gene expression (n = 95) by quantitative real-time polymerase chain reaction. RESULTS: A large number of lipoprotein subclasses, myristoylcarnitine and palmitoylcarnitine, and kynurenine were reduced when SFAs were replaced with PUFAs. In contrast, bile acids, proprotein convertase subtilisin/kexin type 9, acetate, and acetoacetate were increased by the intervention. Some amino acids were also altered by the intervention. The mRNA levels of LXRA and LDLR were increased, in addition to several liver X receptor α target genes and genes involved in inflammation, whereas the mRNA levels of UCP2 and PPARD were decreased in peripheral blood mononuclear cells after replacing SFAs with PUFAs. Partial least squares-discriminant analysis showed that the 30 most important variables that contributed to class separation spanned all classes of biomarkers, and was in accordance with the univariate analysis. CONCLUSIONS: Applying metabolomics in randomized controlled dietary intervention trials has the potential to extend our knowledge of the biological and molecular effects of dietary fat quality. This study was registered at clinicaltrials.gov as NCT01679496.


Assuntos
Dieta , Gorduras na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Comportamento Alimentar , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas/sangue , Ácido Acético/sangue , Acetoacetatos/sangue , Aminoácidos/sangue , Ácidos e Sais Biliares/sangue , LDL-Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/sangue , Método Duplo-Cego , Ácidos Graxos/administração & dosagem , Ácidos Graxos/sangue , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/uso terapêutico , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Hipercolesterolemia/dietoterapia , Hipercolesterolemia/genética , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Pessoa de Meia-Idade , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo
13.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(8): 1124-1133, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31054325

RESUMO

Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms of diosgenin (DG) that promote cholesterol homeostasis and alleviate hypercholesterolemia remain elusive. To investigate the effects and molecular mechanisms of the promotion of cholesterol metabolism by DG, a rat model of hypercholesterolemia was induced by providing a high-fat diet for 4 weeks. After 4 weeks, the rats were intragastrically administered high-dose DG (0.3 g/kg/d), low-dose DG (0.15 g/kg/d) or simvastatin (4 mg/kg/d) once a day for 8 weeks. The serum and hepatic cholesterol were tested, the mRNA and protein expression levels of Niemann-Pick C1-Like 1 (NPC1L1), liver X receptor-α (LXR-α) and the ATP-binding cassette G5/G8 (ABCG5/G8) transporters were measured. The results indicate that DG could reduce body weight, decrease the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, liver total cholesterol and free cholesterol levels compared to those in the controls. Simultaneously, liver tissue pathological morphology analyses revealed that DG could attenuate hepatic steatosis compared to that in the high-fat diet group. Further investigation demonstrated that DG significantly decreased the expression of NPC1L1 and LXR-α in the intestine and markedly increased the expression of ABCG5/G8 in the liver and intestine. Compared to the high-fat diet group, the rats in the DG-treated groups ameliorated hypercholesterolemia in a dose- and time-dependent manner. These data suggest that DG may not only inhibit intestinal cholesterol absorption by downregulating NPC1L1 but also enhance cholesterol excretion by increasing the expression of ABCG5/G8. DG could be a new candidate for the prevention of hypercholesterolemia.


Assuntos
Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/agonistas , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/agonistas , Colesterol/metabolismo , Diosgenina/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Animais , Anticolesterolemiantes , Colesterol/sangue , Diosgenina/farmacologia , Hipercolesterolemia/metabolismo , Hipercolesterolemia/prevenção & controle , Mucosa Intestinal/metabolismo , Intestinos , Fígado/metabolismo , Ratos
14.
Mol Med Rep ; 19(6): 5185-5194, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059080

RESUMO

Sphincter of Oddi dysfunction (SOD) is a benign obstructive disorder predominantly resulting from spasms of the SO. Pharmacological therapies aim to induce SO relaxation; the hypercholesterolemic (HC) rabbit is the only SOD model available for study. In the present study, SO muscle strips, intracellular calcium ion concentrations and the mRNA expression levels of the α1C subunit of the L­type calcium channel in the SO muscle cells of HC rabbits were employed to investigate the effects of paeoniflorin (PF). Alterations in L­type calcium channel α subunit 1C mRNA and protein expression in SO cells with HC following the application of different concentrations of PF were determined by reverse transcription­quantitative polymerase chain reaction and western blotting. The whole cell patch clamp technique was used to observe the effects of different concentrations of paeoniflorin on L­type calcium channel current. The results of the present study demonstrated that PF induced the relaxation of SO muscle strips and reduced the intracellular calcium concentration in the SO muscle cells of HC rabbits. In addition, PF decreased the mRNA expression levels of the α1C subunit of the L­type calcium channel and reduced the L­type calcium channel current in SO cells. These results suggested that the mechanism underlying the relaxation of the SO muscle by PF may be associated with the reduction of calcium ion influx via L­type calcium channels.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Canais de Cálcio Tipo L/metabolismo , Glucosídeos/farmacologia , Hipercolesterolemia/patologia , Monoterpenos/farmacologia , Músculos/efeitos dos fármacos , Esfíncter da Ampola Hepatopancreática/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Cálcio/metabolismo , Canais de Cálcio Tipo L/genética , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Glucosídeos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Masculino , Monoterpenos/uso terapêutico , Tono Muscular/efeitos dos fármacos , Músculos/fisiologia , Técnicas de Patch-Clamp , Coelhos
15.
Food Funct ; 10(5): 2888-2893, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31070609

RESUMO

The aim of this study was to investigate whether supplementation with nattokinase, which is considered one of the most active functional ingredients found in natto, alters hemostatic factors. Subjects presenting with hypercholesterolemia (serum cholesterol: 200-280 mg dL-1) were randomly divided into nattokinase and placebo groups (n = 50, respectively). No significant between-group differences were found at baseline in collagen-epinephrine closure time (C-EPI CT), prothrombin time (PT), or activated partial thromboplastin time (aPTT). After 8 weeks of treatment, the nattokinase group exhibited significant increases in C-EPI CT, PT, and aPTT. The nattokinase group showed significantly greater increases in C-EPI CT (P = 0.001) and aPTT (P = 0.016) than the placebo group. Moreover, at 8 weeks, the nattokinase group showed a significantly higher C-EPI CT than the placebo group (P = 0.001). Additionally, a significant correlation between PT and aPTT was observed (r = 0.491, P < 0.001). In conclusion, nattokinase supplementation was associated with prolonged C-EPI CT and aPTT in nondiabetic and borderline-to-moderate hypercholesterolemic subjects.


Assuntos
Colágeno/metabolismo , Suplementos Nutricionais/análise , Epinefrina/metabolismo , Hipercolesterolemia/tratamento farmacológico , Alimentos de Soja/análise , Subtilisinas/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Tempo de Protrombina
16.
Nutrients ; 11(5)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31096723

RESUMO

The plasma membranes of the human lens fiber cell are overloaded with cholesterol that not only saturates the phospholipid bilayer of these membranes but also leads to the formation of pure cholesterol bilayer domains. Cholesterol level increases with age, and for older persons, it exceeds the cholesterol solubility threshold, leading to the formation of cholesterol crystals. All these changes occur in the normal lens without too much compromise to lens transparency. If the cholesterol content in the cell membranes of other organs increases to extent where cholesterol crystals forma, a pathological condition begins. In arterial cells, minute cholesterol crystals activate inflammasomes, induce inflammation, and cause atherosclerosis development. In this review, we will indicate possible factors that distinguish between beneficial and negative cholesterol action, limiting cholesterol actions to those performed through cholesterol in cell membranes and by cholesterol crystals.


Assuntos
Colesterol na Dieta/administração & dosagem , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Cristalino/irrigação sanguínea , Cristalino/fisiologia , Animais , Humanos
17.
J Agric Food Chem ; 67(22): 6150-6159, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31117552

RESUMO

Consumptions of fruit seed oils and meals could potentially improve cardiovascular health by reducing plasma total cholesterol and low-density lipoprotein (LDL). The study objective was to compare the effectiveness of expeller-pressed and solvent-extracted grape, tomato, pomegranate seed oils, and defatted pomegranate meals in lowering plasma and hepatic cholesterol using hamster models. Hamsters were fed with fruit seed oils (FSO), defatted pomegranate seed meals (PDM), or control diets. After a 3-week feeding period, plasma total triglycerides of treatment diets were significantly lower. FSO also reduced total, very-low-density lipoprotein- (VLDL), and LDL-cholesterols, while PDM only lowered VLDL-cholesterols. Decreases in low-density and high-density lipoproteins (LDL/HDL) ratios were also observed in most treatments. In liver, triglycerides, total, and free cholesterol levels did not vary between control and treatments. There were no significant differences in lipid modulating properties between solvent-extracted and expeller-pressed oils. In conclusion, partial replacements of saturated fat in high-fat diets with tomato, pomegranate, and grape seed oils could effectively reduce plasma triglyceride levels and improve HDL/LDL ratios.


Assuntos
Anticolesterolemiantes/metabolismo , Hipercolesterolemia/dietoterapia , Lythraceae/química , Óleos Vegetais/metabolismo , Sementes/química , Animais , Anticolesterolemiantes/química , Colesterol/metabolismo , Cricetinae , Humanos , Hipercolesterolemia/metabolismo , Lipoproteínas HDL/sangue , Fígado/metabolismo , Lythraceae/metabolismo , Masculino , Mesocricetus , Óleos Vegetais/química , Sementes/metabolismo , Triglicerídeos/metabolismo
18.
Pharmacol Rep ; 71(3): 417-421, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31003151

RESUMO

BACKGROUND: Individuals with non-classic congenital adrenal hyperplasia (NC-CAH) often show evidence of hyperandrogenism, including premature pubarche, accelerated linear growth velocity, short final height, hirsutism, acne, alopecia, impaired ovulation, menstrual dysfunction and subfertility. Although statins were found to reduce elevated levels of androgens in subjects with this disorder, no previous study has investigated whether 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors affect cardiometabolic risk factors in patients with NC-CAH. METHODS: We studied 12 women with NC-CAH, 6 of whom because of coexisting hypercholesterolemia received atorvastatin (20-40 mg daily). Circulating levels of lipids, glucose homeostasis markers, plasma levels of androgens, 17-hydroxyprogesterone, high-sensitivity C-reactive protein (hsCRP), uric acid, fibrinogen, homocysteine and 25-hydroxyvitamin D, as well as urinary albumin-to-creatinine ratio (UACR) were determined at the beginning of the study and 12 weeks later. RESULTS: Beyond affecting plasma lipids, atorvastatin reduced circulating levels of testosterone, dehydroepiandrosterone sulphate, androstenedione and 17-hydroxyprogesterone, and decreased free androgen index. Moreover, atorvastatin caused a decrease in plasma levels/urinary loss of uric acid, hsCRP, homocysteine and UACR, and insignificantly increased circulating levels of 25-hydroxyvitamin D. The drug produced no effect on plasma fibrinogen. The effect of atorvastatin on hsCRP, uric acid, homocysteine, 25-hydroxyvitamin D and UACR correlated with the magnitude of reduction in 17-hydroxyprogesterone and androgens. CONCLUSION: Our results suggest that statin therapy reduces cardiometabolic risk in women with NC-CAH.


Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Atorvastatina/farmacologia , Doenças Cardiovasculares/induzido quimicamente , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/metabolismo , Adulto , Androgênios/sangue , Androgênios/metabolismo , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Sulfato de Desidroepiandrosterona/sangue , Feminino , Fibrinogênio/metabolismo , Homocisteína/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Projetos Piloto , Fatores de Risco , Testosterona/sangue , Ácido Úrico/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
19.
Food Funct ; 10(5): 2515-2527, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-30990213

RESUMO

We previously demonstrated that the combination of phytosterols (PS) and curcumin administered as dietary supplements significantly lowers LDL-cholesterol (LDL-C) more than either treatment alone. The aim of this study was to investigate the effects of this combination in a novel food (bread) on plasma lipid profiles in hypercholesterolaemic individuals. In a double-blinded, placebo-controlled, 2 × 2 factorial trial, participants were randomised to receive bread fortified with placebo (PL), 2.3 g PS (PS), 228 mg curcumin (CC) or a combination of 2.3 g PS and 228 mg CC (PS-CC) daily for four weeks. Primary outcomes were fasting plasma lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)] and secondary outcomes were plasma LDL-particle (LDL-P) profile: LDL-P number and LDL-P size. Cardiovascular disease (CVD) risk (Framingham Risk Algorithm) was also explored. There was no significant difference between PL and CC or PS and PS-CC on blood lipids or CVD risk; therefore, groups were pooled for final analysis: the PL and CC group (PL-C, n = 36) and the PS and PS-CC group (PS-C, n = 39). PS-C significantly lowered TC (-0.52 mmol L-1, p < 0.0001), LDL-C (-0.49 mmol L-1, p < 0.0001) and CVD risk (-1.1 absolute %, p = 0.0005) compared to the PL-C group. Reductions from baseline in the PS-C group compared to that in the PL-C group were 7.6% and 10.6% for TC and LDL-C, respectively, and statistically significant (p < 0.0001). CVD-risk in the PS-C group reduced significantly (-12.7%) compared to that in the PL-C group (p = 0.0005). HDL-C and TG remained unchanged. The LDL-P number significantly decreased in the PS-C group by 124.33 nmol L-1 compared to that in the PL-C group (p = 0.005) and both groups showed a significant decrease in LDL-P size (p < 0.01); however, the absolute nm change in LDL-P size did not differ between groups and the percent change in LDL-P size in the PS-C group was borderline significant (-0.89%, p = 0.05) compared to that in the PL-C group. Regular consumption of PS-enriched bread with or without curcumin lowers blood cholesterol; however, curcumin alone did not influence blood lipids. Bread may be a convenient means of delivering PS with greater compliance for reducing the blood cholesterol concentration.


Assuntos
Pão/análise , Curcumina/metabolismo , Hipercolesterolemia/dietoterapia , Lipoproteínas/metabolismo , Fitosteróis/metabolismo , Adolescente , Adulto , Idoso , Austrália , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Curcumina/análise , Feminino , Humanos , Hipercolesterolemia/metabolismo , Lipoproteínas/química , Masculino , Pessoa de Meia-Idade , Fitosteróis/análise , Triglicerídeos/sangue , Adulto Jovem
20.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(7): 976-984, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30905828

RESUMO

Long-term exposure to hypercholesterolemia induces the development of skin xanthoma's characterized by the accumulation of lipid-laden foam cells in humans and in mice. Early skin changes in response to hypercholesterolemia are however unknown. In this study, we investigated the skin lipid composition and associated barrier function in young adult low-density lipoprotein receptor knockout (LDLR-/-) and apolipoprotein E knockout (APOE-/-) mice, two commonly used hypercholesterolemic mouse models characterized by the accumulation of apolipoprotein B containing lipoproteins. No differences were observed on cholesterol content in the epidermis in LDLR-/- mice nor in the more extremely hypercholesterolemic APOE-/- mice. Interestingly, the free fatty acid profile in the APOE-/- epidermis shifted towards shorter and unsaturated chains. Genes involved in the synthesis of cholesterol and fatty acids were downregulated in APOE-/- skin suggesting a compensation for the higher influx of plasma lipids, most probably as cholesteryl esters. Importantly, in vivo transepidermal water loss and permeability studies with murine lipid model membranes revealed that the lipid composition of the APOE-/- skin resulted in a reduced skin barrier function. In conclusion, severe hypercholesterolemia associated with increased apolipoprotein B containing lipoproteins affects the epidermal lipid composition and its protective barrier.


Assuntos
Apolipoproteínas E/genética , Epiderme/química , Hipercolesterolemia/fisiopatologia , Lipídeos/química , Animais , Apolipoproteínas B/metabolismo , Apolipoproteínas E/deficiência , Ácidos Graxos/metabolismo , Hipercolesterolemia/metabolismo , Lipídeos/análise , Camundongos , Permeabilidade , Receptores de LDL/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA