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1.
Adv Clin Chem ; 90: 25-80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31122611

RESUMO

Acute-phase reactant serum amyloid A (A-SAA) plays an important role in acute and chronic inflammation and is used in clinical laboratories as an indicator of inflammation. Although both A-SAA and C-reactive protein (CRP) are acute-phase proteins, the detection of A-SAA is more conclusive than the detection of CRP in patients with viral infections, severe acute pancreatitis, and rejection reactions to kidney transplants. A-SAA has greater clinical diagnostic value in patients who are immunosuppressed, patients with cystic fibrosis who are treated with corticoids, and preterm infants with late-onset sepsis. Nevertheless, for the assessment of the inflammation status and identification of viral infection in other pathologies, such as bacterial infections, the combinatorial use of A-SAA and other acute-phase proteins (APPs), such as CRP and procalcitonin (PCT), can provide more information and sensitivity than the use of any of these proteins alone, and the information generated is important in guiding antibiotic therapy. In addition, A-SAA-associated diseases and the diagnostic value of A-SAA are discussed. However, the relationship between different A-SAA isotypes and their human diseases are mostly derived from research laboratories with limited clinical samples. Thus, further clinical evaluations are necessary to confirm the clinical significance of each A-SAA isotype. Furthermore, the currently available A-SAA assays are based on polyclonal antibodies, which lack isotype specificity and are associated with many inflammatory diseases. Therefore, these assays are usually used in combination with other biomarkers in the clinic.


Assuntos
Reação de Fase Aguda , Doença , Inflamação/sangue , Inflamação/diagnóstico , Proteína Amiloide A Sérica/análise , Amiloidose/sangue , Amiloidose/diagnóstico , Amiloidose/metabolismo , Animais , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/metabolismo , Humanos , Inflamação/metabolismo , Hepatopatias/sangue , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/metabolismo , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/metabolismo , Proteína Amiloide A Sérica/metabolismo
2.
Nat Commun ; 10(1): 1981, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31040273

RESUMO

Cardiovascular and metabolic disease (CMD) remains a main cause of premature death worldwide. Berberine (BBR), a lipid-lowering botanic compound with diversified potency against metabolic disorders, is a promising candidate for ameliorating CMD. The liver is the target of BBR so that liver-site accumulation could be important for fulfilling its therapeutic effect. In this study a rational designed micelle (CTA-Mic) consisting of α-tocopheryl hydrophobic core and on-site detachable polyethylene glycol-thiol shell is developed for effective liver deposition of BBR. The bio-distribution analysis proves that the accumulation of BBR in liver is increased by 248.8% assisted by micelles. Up-regulation of a range of energy-related genes is detectable in the HepG2 cells and in vivo. In the high fat diet-fed mice, BBR-CTA-Mic intervention remarkably improves metabolic profiles and reduces the formation of aortic arch plaque. Our results provide proof-of-concept for a liver-targeting strategy to ameliorate CMD using natural medicines facilitated by Nano-technology.


Assuntos
Berberina/farmacologia , Hipoglicemiantes/uso terapêutico , Nanotecnologia/métodos , Animais , Células CACO-2 , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Células Hep G2 , Humanos , Hipoglicemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/tratamento farmacológico , Camundongos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
3.
Transl Res ; 210: 26-42, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31121128

RESUMO

Obesity is a major cause of metabolic syndrome and type II diabetes, and it presents with metabolic disorders, such as hyperglycemia, hyperlipidemia, and insulin resistance. Pigment epithelium-derived factor (PEDF), a protein isolated from retinal pigment epithelial cells, has multiple functions, including neuronal protection, antineoplastic effects, and anti-inflammatory activity. The aim of this study is to investigate the antiobesity effects of PEDF. The antiobesity effects of PEDF on fat accumulation, inflammation, energy expenditure, insulin resistance, and obesity-related physiological parameters and protein levels were assessed in high-fat diet (HFD)-induced obese mice in vivo and in 3T3-L1 adipocytes, palmitate (PA)-treated HepG2 cells, and C2C12 myotubes in vitro. In an in vivo assay, PEDF effectively decreased body weight gain, white adipose tissue mass, and inflammation and improved insulin resistance, dyslipidemia, and hyperglycemia in HFD-induced mice. In liver tissue, PEDF decreased lipid accumulation and fibrosis. In an in vitro assay, PEDF diminished the differentiation of 3T3-L1 preadipocytes. We also determined that PEDF promoted lipolysis and prolonged cell cycle progression, through the mTOR-S6K pathway and downstream transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α (CEBP-α), and CEBP-ß. In addition, PEDF decreased reactive oxygen species production in PA-induced HepG2 cells and improved glucose uptake ability in PA-induced HepG2 cells and C2C12 myotubes. In the present study, PEDF protected against HFD-induced obesity and metabolic disorders in mice, inhibited adipogenesis, and improved insulin resistance. These results provide a new potential treatment for obesity in the future.


Assuntos
Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Proteínas do Olho/farmacologia , Doenças Metabólicas/patologia , Fatores de Crescimento Neural/farmacologia , Obesidade/patologia , Obesidade/prevenção & controle , Serpinas/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Clonais , Dieta Hiperlipídica , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Células Hep G2 , Humanos , Inflamação/patologia , Resistência à Insulina , Masculino , Doenças Metabólicas/sangue , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Obesidade/sangue , Obesidade/complicações , Estresse Oxidativo/efeitos dos fármacos , Ácido Palmítico , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
4.
Heart Fail Clin ; 15(3): 371-375, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079695

RESUMO

The model used to explain the pathophysiologic substrate and progressive worsening in chronic heart failure (CHF) is based on the hyperactivity of renin-angiotensin-aldosterone system and adrenergic pathway. Although the neurohormonal medical approach has many advantages, it has several pitfalls, as demonstrated by high rates of CHF mortality and hospitalization. A growing body of evidence has led to the hypothesis that CHF is a multiple hormone deficiency syndrome, characterized by a reduced anabolic drive that has relevant functional and prognostic implications. The aim of this review is to summarize the evidence of reduced drive of main anabolic axes in CHF.


Assuntos
Deficiências Nutricionais/etiologia , Insuficiência Cardíaca , Hormônios/sangue , Doenças Metabólicas/etiologia , Biomarcadores/sangue , Deficiências Nutricionais/sangue , Progressão da Doença , Saúde Global , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Humanos , Doenças Metabólicas/sangue , Morbidade/tendências , Prognóstico
5.
Ecotoxicol Environ Saf ; 178: 94-104, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30999185

RESUMO

Light is involved in many critical physiological or biochemical processes of human beings, such as visual sensing and the production of vitamin D. Recent studies have showed that the lights of different wavelengths have a profound influence in life activities. For example, blue light promotes alertness, whereas green light (GL) induces sleep in mice. On the other hand, metabolic homeostasis is regulated by a variety of factors, including dietary habits and light exposure. Our study aims to study whether certain wavelength of light would affect metabolic status of mice. Mice were divided into normal diet-fed group and high-fat diet (HFD)-fed group, and then exposed to various colors of the light. Physiological parameters, such as body weight, food intake and water drinking were regularly measured. Glucose tolerance test and pyruvate tolerance test were simultaneously performed. After mice were humanely sacrificed, liver histology and serologic analysis were performed for detecting lipid levels. We found that GL group showed obvious glucose intolerance and increased levels of serum and liver lipid contents compared to white light group. Meanwhile, the expression levels of lipid metabolism-related genes were almost down-regulated in liver. Furthermore, melatonin receptor-1b and thyroid hormone receptor-ß expression levels were significantly lowered in liver of GL-treated obese mice, suggesting that these hormone pathways may mediate the changes of lipid metabolism. Our data indicate that GL has a detrimental effect on the energy metabolism and aggravates HFD-induced obesity in mice. In addition to malnutrition, the colors of the lights also have a profound influence in the metabolic homeostasis and should be taken into consideration in the therapy of metabolic disorders.


Assuntos
Dieta Hiperlipídica , Metabolismo Energético/efeitos da radiação , Luz , Metabolismo dos Lipídeos/efeitos da radiação , Doenças Metabólicas/metabolismo , Obesidade/metabolismo , Animais , Peso Corporal/efeitos da radiação , Ingestão de Alimentos/efeitos da radiação , Homeostase/efeitos da radiação , Fígado/efeitos da radiação , Masculino , Doenças Metabólicas/sangue , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue
6.
J Genet ; 982019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945673

RESUMO

Elevated C-reactive protein (CRP) serves as an independent biomarker for acute and chronic inflammation, and is also associated with metabolic diseases. Genomewide loci regulating CRP level in Indian population, a high-risk group for metabolic illness, is unexplored. Therefore, we aimed to discover common polymorphisms associated with plasma CRP level in 4493 Indians of Indo-European origin using genomewide association study. Genomewide strong associations of two known intronic variants in hepatocyte nuclear factor-1 α gene (HNF1A) were identified among Indian subjects. We also detected prior associations of several variants in/near metabolic and inflammatory process genes: APOC1, LEPR, CRP, HNF4A, IL6R and APOE with modest associations. This study confirms that Indians from Indo-European origin display similar core universal genetic factors for CRP levels.


Assuntos
Biomarcadores/análise , Proteína C-Reativa/análise , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Estudo de Associação Genômica Ampla , Inflamação/genética , Doenças Metabólicas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Inflamação/sangue , Inflamação/patologia , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/patologia , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
7.
Nat Commun ; 10(1): 1209, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30872577

RESUMO

Sparse profiling of CpG methylation in blood by microarrays has identified epigenetic links to common diseases. Here we apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal~400), providing high-resolution methylation profiling (>1.3 M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up on adipose-specific regulatory regions under (1) genetic and (2) epigenetic (environmental) regulation via integrational studies. Overall, the comprehensive sequencing of regulatory element methylomes reveals a rich landscape of functional variants linked genetically as well as epigenetically to plasma lipid traits.


Assuntos
Doenças Cardiovasculares/genética , Ilhas de CpG/genética , Epigênese Genética , Doenças Metabólicas/genética , Sequências Reguladoras de Ácido Nucleico/genética , Tecido Adiposo/metabolismo , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Metilação de DNA , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica , Genoma Humano , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Lipídeos/sangue , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos
8.
Nutrients ; 11(3)2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889844

RESUMO

Being overweight has been identified as the main risk factor for the development of metabolic disorders in adults and children. However, recent studies suggest that normal weight individuals are also frequently affected by metabolic abnormalities with underlying mechanisms not yet fully understood. The aim of the present study was to determine if dietary pattern and markers of intestinal permeability, as well as inflammation, differ between normal weight healthy children and normal weight children suffering from metabolic abnormalities. In total, 45 normal weight children aged 5⁻9 years were included in the study, of whom nine suffered from metabolic abnormalities. Anthropometric data, dietary intake and markers of inflammation, as well as intestinal permeability, were assessed in fasting blood samples. Neither BMI nor BMI-SDS differed between groups; however, children with metabolic abnormalities had a significantly larger waist circumference (+~5 cm) and a higher leptin to adiponectin ratio. While plasma leptin levels are significantly higher in normal weight children with metabolic abnormalities, neither TNF α nor sCD14, adiponectin, PAI-1 or IL-6 plasma levels differed between groups. Despite similar total calorie and macronutrient intake between groups, mean total fructose and total glucose intake (resulting mainly from sugar sweetened beverages, fruits and sweets) were higher in children with metabolic abnormalities than in healthy children. Time spent physically active was significantly higher in healthy normal weight children whereas time spent physically inactive was similar between groups. Furthermore, bacterial endotoxin levels were significantly higher in the peripheral plasma of normal weight children with metabolic abnormalities than in healthy normal weight children. Our results suggest that metabolic disorders in normal weight children are associated with a high monosaccharide intake and elevated bacterial endotoxin as well as leptin plasma levels, the latter also discussed as being indicative of visceral adiposity.


Assuntos
Índice de Massa Corporal , Endotoxinas/sangue , Glucose/efeitos adversos , Gordura Intra-Abdominal/metabolismo , Doenças Metabólicas/etiologia , Monossacarídeos/efeitos adversos , Circunferência da Cintura , Adiponectina/sangue , Criança , Pré-Escolar , Dieta , Açúcares da Dieta/administração & dosagem , Açúcares da Dieta/efeitos adversos , Ingestão de Energia , Comportamento Alimentar , Feminino , Frutose/administração & dosagem , Frutose/efeitos adversos , Glucose/administração & dosagem , Humanos , Interleucina-6/sangue , Intestinos , Leptina/sangue , Masculino , Doenças Metabólicas/sangue , Monossacarídeos/administração & dosagem , Inibidor 1 de Ativador de Plasminogênio/sangue , Valores de Referência , Fator de Necrose Tumoral alfa/sangue
9.
PLoS One ; 14(2): e0211774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30735532

RESUMO

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) is a sensitive biomarker of systemic inflammation and is related to the development and progression of cardiometabolic diseases. Beyond individual-level determinants, characteristics of the residential physical and social environment are increasingly recognized as contextual determinants of systemic inflammation and cardiometabolic risks. Based on a large nationwide sample of adults in Germany, we analyzed the cross-sectional association of hsCRP with residential environment characteristics. We specifically asked whether these associations are observed independent of determinants at the individual level. METHODS: Data on serum hsCRP levels and individual sociodemographic, behavioral, and anthropometric characteristics were available from the German Health Interview and Examination Survey for Adults (2008-2011). Area-level variables included, firstly, the predefined German Index of Socioeconomic Deprivation (GISD) derived from the INKAR (indicators and maps on spatial and urban development in Germany and Europe) database and, secondly, population-weighted annual average concentration of particulate matter (PM10) in ambient air provided by the German Environment Agency. Associations with log-transformed hsCRP levels were analyzed using random-intercept multi-level linear regression models including 6,768 participants aged 18-79 years nested in 162 municipalities. RESULTS: No statistically significant association of PM10 exposure with hsCRP was observed. However, adults residing in municipalities with high compared to those with low social deprivation showed significantly elevated hsCRP levels (change in geometric mean 13.5%, 95%CI 3.2%-24.7%) after adjusting for age and sex. The observed relationship was independent of individual-level educational status. Further adjustment for smoking, sports activity, and abdominal obesity appeared to markedly reduce the association between area-level social deprivation and hsCRP, whereas all individual-level variables contributed significantly to the model. CONCLUSIONS: Area-level social deprivation is associated with higher systemic inflammation and the potentially mediating role of modifiable risk factors needs further elucidation. Identifying and assessing the source-specific harmful components of ambient air pollution in population-based studies remains challenging.


Assuntos
Proteína C-Reativa/metabolismo , Bases de Dados Factuais , Exposição Ambiental/efeitos adversos , Cardiopatias , Doenças Metabólicas , Modelos Biológicos , Material Particulado/efeitos adversos , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Alemanha , Cardiopatias/sangue , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Humanos , Estudos Longitudinais , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Pessoa de Meia-Idade , Fatores de Risco
10.
Arch Oral Biol ; 99: 183-189, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30731368

RESUMO

OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory mucosal lesion and systemic disease. In OLP, reticular type is the most common presentation of the disease. However, little is known about it. The aim of this study was to analyze the pathogenesis of reticular OLP and its possible associations with the pathological changes in other organ systems through serum-based metabolomics. METHODS: Blood samples were obtained from 16 reticular OLP patients and 24 control subjects. Liquid chromatography (LC)-mass spectrometry (MS) system was used to identify differentially expressed metabolites. The pathways analysis was performed by MetaboAnalyst. Pathological network was constructed by Cytoscape software. RESULTS: Totally, 31 modulated metabolites were identified, whose dysregulations affected 25 metabolic pathways and 7 pathological processes in the disease. Through an impact-value screen (impact-value>0.1), 6 pathways were selected as the significantly dysregulated pathways. Pathological network showed that these metabolites participated in 7 pathological processes, that is, apoptosis process, DNA damage and repair disorder, oxidative stress injury, carbohydrate metabolism disorder, mood dysfunction, inflammatory lesion, and other pathological process. CONCLUSION: The study demonstrated that reticular OLP could cause the dysregulations of the metabolites in serum, which might be also further linked to other organ and systemic diseases through the blood system, such as diabetes, sleep disorders, and depression, etc.


Assuntos
Líquen Plano Bucal/sangue , Líquen Plano Bucal/metabolismo , Metabolômica , Mucosa Bucal/metabolismo , Adolescente , Adulto , Apoptose , Metabolismo dos Carboidratos , China , Cromatografia Líquida , Dano ao DNA , Reparo do DNA , Feminino , Humanos , Líquen Plano Bucal/patologia , Masculino , Espectrometria de Massas , Doenças Metabólicas/sangue , Redes e Vias Metabólicas , Metaboloma , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Análise Multivariada , Estresse Oxidativo , Software , Adulto Jovem
11.
Dis Model Mech ; 12(2)2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30733237

RESUMO

Endoplasmic reticulum (ER) stress has been causatively linked to the onset of various pathologies. However, whether and how inherent variations in the resulting unfolded protein response (UPR) affect predisposition to ER-stress-associated metabolic conditions remains to be established. By using genetically diverse deer mice (Peromyscus maniculatus) as a model, we show that the profile of tunicamycin-induced UPR in fibroblasts isolated at puberty varies between individuals and predicts deregulation of lipid metabolism and diet-induced hepatic steatosis later in life. Among the different UPR targets tested, CHOP (also known as Ddit3) more consistently predicted elevated plasma cholesterol and hepatic steatosis. Compared with baseline levels or inducibility, the maximal intensity of the UPR following stimulation best predicts the onset of pathology. Differences in the expression profile of the UPR recorded in cells from different populations of deer mice correlate with the varying response to ER stress in altitude adaptation. Our data suggest that the response to ER stress in cultured cells varies among individuals, and its profile early in life might predict the onset of ER-stress-associated disease in the elderly.This article has an associated First Person interview with the first author of the paper.


Assuntos
Doenças Metabólicas/patologia , Resposta a Proteínas não Dobradas , Altitude , Animais , Animais não Endogâmicos , Células Cultivadas , Dieta Hiperlipídica , Suscetibilidade a Doenças/sangue , Suscetibilidade a Doenças/patologia , Fígado Gorduroso/patologia , Feminino , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Lipídeos/sangue , Masculino , Doenças Metabólicas/sangue , Peromyscus , Fatores de Transcrição/metabolismo
12.
Dis Markers ; 2019: 3102870, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30805036

RESUMO

Chronic low-grade, systemic inflammation is a well-characterized risk factor in the development of chronic metabolic diseases, such as cardiovascular disease, type 2 diabetes, and metabolic syndrome. Diet could be an effective strategy for reducing inflammation associated with chronic disease. While anti-inflammatory properties of isolated dietary bioactive and functional foods have been routinely studied, the evaluation of dietary patterns on inflammation warrants further review-especially given the recent inclusion of dietary pattern recommendations into dietary guidelines and policies. Therefore, the objective of this narrative review is to examine current evidence linking diet to low-grade, systemic inflammation within the context of chronic disease. Specifically, we provide an update on the findings from human trials that have characterized anti-inflammatory properties of dietary patterns, defined by various methods and indexes. Given the complexity of interpreting results from dietary pattern analysis, we further present recent evidence on the anti-inflammatory roles of isolated bioactive nutrients and functional foods that are common components of distinct dietary patterns, in addition to considerations for interpreting dietary pattern research, population-specific dietary recommendations, and future studies. Overall, we observe a vast range of variability in the evidence from observational studies that have evaluated the relationships between healthy dietary patterns and inflammatory markers. These studies highlight the need for additional intervention studies with study designs that account for metabolic status, diversity in populations, breadth of inflammatory measurements, fasting vs. postprandial effects of diet, and control of confounding factors (e.g., genotype, microbiome profiles, and dietary adherence) in order to better understand the effect that diet has, as a whole, on inflammation. These strategies will help to strengthen diet recommendations aimed at reducing inflammation and chronic disease risk.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Citocinas/sangue , Dieta , Doenças Metabólicas/prevenção & controle , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Humanos , Doenças Metabólicas/sangue , Recomendações Nutricionais
13.
Nutrients ; 11(1)2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30634478

RESUMO

Non-cholesterol sterols are validated biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis. However, their use in metabolic disturbances has not been systematically explored. Therefore, we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders. Potentially relevant studies were retrieved by a systematic search of three databases in July 2018 and ninety-four human studies were included. Cholesterol-standardized levels of campesterol, sitosterol and cholestanol were collected to reflect cholesterol absorption and those of lathosterol and desmosterol to reflect cholesterol synthesis. Their use as biomarkers was examined in the following metabolic disorders: overweight/obesity (n = 16), diabetes mellitus (n = 15), metabolic syndrome (n = 5), hyperlipidemia (n = 11), cardiovascular disease (n = 17), and diseases related to intestine (n = 16), liver (n = 22) or kidney (n = 2). In general, markers for cholesterol absorption and synthesis displayed reciprocal patterns, showing that cholesterol metabolism is tightly regulated by the interplay of intestinal absorption and endogenous synthesis. Distinctive patterns for cholesterol absorption or cholesterol synthesis could be identified, suggesting that metabolic disorders can be classified as 'cholesterol absorbers or cholesterol synthesizers'. Future studies should be performed to confirm or refute these findings and to examine whether this information can be used for targeted (dietary) interventions.


Assuntos
Biomarcadores/sangue , Colesterol/metabolismo , Doenças Metabólicas/sangue , Esteróis/sangue , Doenças Cardiovasculares/sangue , Colesterol/análogos & derivados , Colesterol/sangue , Desmosterol/sangue , Diabetes Mellitus/sangue , Humanos , Absorção Intestinal , Enteropatias/sangue , Nefropatias/sangue , Hepatopatias/sangue , Obesidade/sangue , Sobrepeso/sangue , Fitosteróis/sangue , Sitosteroides/sangue
14.
Diabetes Metab Syndr ; 13(1): 596-602, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641772

RESUMO

The aims were to assess the prevalence and characteristics of dyslipidemia phenotypes in a Romanian population-based sample from the PREDATORR study. METHODS: PREDATORR was an epidemiological study with a cross-sectional, cluster random sampling design. Participants were classified into four dyslipidemia phenotypes based on the NCEP ATP III criteria: isolated hypertrigliceridemia, isolated hypoHDL-C, isolated hyperLDL-C and mixed dyslipidemia (≥2 standard lipid abnormalities). Overall, 2656 were included in the analysis by dyslipidemia phenotypes. RESULTS: An estimated 67.1% of Romanian adults have at least one lipid abnormality: 27.5% (95%CI26.0-28.9%) have elevated TG, 29.4% (95%CI27.9-30.8%) have low HDL-C and 47.8% (95%CI46.3-49.2%) have elevated LDL-C (26.2% had LDL-C levels ≥2.58 mmol/l associated with CHD or CHD risk equivalent). Also, 30% Romanian adults have mixed dyslipidemia with 7.6% (95%CI6.1-9.0%) having all three lipid abnormalities. THE AGE: and sex-adjusted prevalence of isolated dyslipidemia phenotypes in Romanian adult population was 23.7% (95%CI22.2-25.1%) for hyperLDL-Cholesterolemia, 9.3% (95%CI7.8-10.7%) for hypoHDL-Cholesterolemia and 4.1% (95%CI2.6-5.5%) for hypertriglyceridemia. Among participants with triglycerides ≥2.25 mmol/l, 15.2% (95%CI13.7-16.6%) of Romanian adults have non-HDL-C levels ≥3.36 mmol/l. CONCLUSIONS: The PREDATORR survey indicated a high prevalence of dyslipidemia phenotypes in the Romanian population aged 20-79 years, providing data on its association with several cardiometabolic risk factors.


Assuntos
Doenças Cardiovasculares/epidemiologia , Dislipidemias/epidemiologia , Rim/fisiologia , Doenças Metabólicas/epidemiologia , Vigilância da População , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Análise por Conglomerados , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Pessoa de Meia-Idade , Vigilância da População/métodos , Prevalência , Fatores de Risco , Romênia/epidemiologia
15.
Psychiatry Res ; 272: 643-648, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30616135

RESUMO

Bipolar disorder (BD), a psychiatric illness, results partly as a side effect of psychotropic medications and presents a high risk of metabolic disturbance. Fibroblast growth factor 21 (FGF21) is as an important regulator in carbohydrate and lipid metabolism. In this study, we investigated the serum levels of FGF21 and analyzed its association with metabolic parameters in bipolar mania patients at pre- and post-treatment with psychotropic medications. Bipolar mania inpatients (n = 99) and healthy controls (n = 99) were included at baseline; the patients were followed up after four-week treatment. Serum levels of FGF21 and several metabolic parameters were measured by appropriate detection methods. We found that baseline serum FGF21 levels were significantly higher in bipolar manic patients when compared to that in controls. After four-week medication, FGF21 levels were found to be decreased in patients when compared to the baseline suggesting that FGF21 may be associated with the psychopathology of bipolar mania. Moreover, FGF21 levels were found to be negatively correlated with the serum triglycerides (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), glucose (Glu), and Body Mass Index (BMI). In addition, our data also indicates that FGF21 may monitor and/or prevent the metabolic abnormalities induced by psychotropic drugs.


Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/sangue , Doenças Metabólicas/sangue , Doenças Metabólicas/induzido quimicamente , Psicotrópicos/uso terapêutico , Adulto , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico , Índice de Massa Corporal , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Glucose/metabolismo , Humanos , Masculino , Doenças Metabólicas/diagnóstico , Pessoa de Meia-Idade , Psicotrópicos/efeitos adversos
16.
Diabetes Metab Syndr ; 13(1): 278-283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641712

RESUMO

AIMS: Diabetic nephropathy is known to be an independent risk factor in the progression of renal and cardiovascular disorders. Due to the association between vitamin D deficiency and diabetic nephropathy, vitamin D deficiency in the diabetic nephropathy population, this study conducted to examine the effects of Vitamin D3 on metabolic and inflammatory parameters in patients with diabetic nephropathy. METHODS: This eight-week, randomized, double-blind, placebo-controlled trial was carried out on 50 diabetic nephropathy patients with marginal status of vitamin D. Participants were randomly assigned to two groups: control and intervention. Participants received a vitamin D3 (50000 IU) supplement weekly on a specific day. Fasting blood samples were collected from all patients at their entry to the study, and eight weeks after intervention. RESULTS: Analyses showed significance differences in physical activity between the intervention and placebo groups (P = 0.018). There were no significant differences between the percentage changes of HbA1c, insulin and, inflammatory parameters such as TNF-α and IL-6 (P > 0.05), while the percentage change of FBS was significantly higher in the placebo group compared to the treatment one (P < 0.0001). Lower levels of FBS (P < 0.0001), insulin (P < 0.069), HOMA-IR (P < 0.001), TNF-α (P< 0.002) and IL-6 (P < 0.037) were found after supplementation in treatment group. However, the phosphorous and protein percentage change in urine were lower (P = 0.07) and higher (P = 0.003) between groups. CONCLUSIONS: It was found that vitamin D supplementation can be regarded as an effective way to prevent the progression of diabetic nephropathy by reducing levels of proteinuria, and inflammatory markers such as TNF-α and IL-6.


Assuntos
Colecalciferol/administração & dosagem , Nefropatias Diabéticas/prevenção & controle , Suplementos Nutricionais , Inflamação/prevenção & controle , Doenças Metabólicas/prevenção & controle , Deficiência de Vitamina D/complicações , Vitaminas/administração & dosagem , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Colecalciferol/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/etiologia , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/etiologia , Pessoa de Meia-Idade , Prognóstico , Vitaminas/sangue , Adulto Jovem
17.
J Pediatr Endocrinol Metab ; 32(2): 135-142, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30685743

RESUMO

Background To develop a diagnostic assessment tool, using clinical, biochemical and sonographic markers, to help clinicians in the differential diagnosis of functional oligomenorrhea (FO) and endocrine-metabolic oligomenorrhea (EMO). Methods Sixty-two adolescents with oligomenorrhea without evident hormonal imbalances or severe energy deficit were selected. They were divided into two groups (EMO and FO) and they all underwent the following assessment: physical examination (height, weight, presence of hirsutism or acne), blood exams and transabdominal ultrasonography. The biochemical markers included: hemoglobin, thyrotropin stimulating hormone (TSH), prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), free (FT) and total testosterone (TT), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG). Uterine and ovarian volume, ovarian morphology, endometrial thickness and pulsatility index (PI) of uterine arteries were evaluated with ultrasound. Results Body mass index (BMI), hemoglobin, LH levels and LH/FSH ratio were significantly higher in women with EMO than in those with FO. Increased androgens values were found in the EMO group, but only A and FT were significantly different (p=0.04). Ovarian volume and uterine artery PI were the only ultrasound features significantly different, with higher values in the EMO population (p<0.05). Considering these variables, with a receiving characteristic operating curve, new cut-offs were calculated, and a diagnostic assessment tool elaborated (area under curve [AUC] 0.88, specificity 99%, sensibility 59%, p<0.001]. Conclusions This diagnostic tool, specific for adolescents, could be useful in the management of oligomenorrhea. Recognizing and distinguishing EMO and FO is very important in order to establish an appropriate treatment and a correct follow-up.


Assuntos
Biomarcadores/sangue , Doenças do Sistema Endócrino/diagnóstico , Hormônios Esteroides Gonadais/sangue , Doenças Metabólicas/diagnóstico , Oligomenorreia/diagnóstico , Adolescente , Diagnóstico Diferencial , Doenças do Sistema Endócrino/sangue , Feminino , Seguimentos , Humanos , Masculino , Doenças Metabólicas/sangue , Oligomenorreia/sangue , Prognóstico
18.
Ecotoxicol Environ Saf ; 170: 391-398, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30550969

RESUMO

BACKGROUND: Plasticizer di-2-ethylhexyl phthalate (DEHP) can induce lipid metabolic disorder. There was a chronic low level inflammatory response in adipose tissue of patients with lipid metabolic disorder. But the effect of inflammation on lipid metabolic disorder induced by DEHP is unclear. The present study was undertaken to explore the effect of di-2-ethylhexyl phthalate on inflammation and lipid metabolic disorder in rats. METHODS: Eighty healthy 21-day-old Wistar rats were randomly divided into 4 groups and administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/ d for 8 weeks. Morphological changes of adipose tissue, the levels of IL-1ß, TNF-α, LEP, and ADP in rat serum and adipose tissue, the serum TC, TG, HDL-C and LDL-C, the mRNA and protein expression levels of lipid metabolism-related gene CEBP/ß and inflammation-related gene CD68 were measured. RESULTS: After exposure to DEHP, the weight of rats in the high dose group was significantly higher than that in the control group (p < 0.05). And the number of adipose tissue cells in the medium-dose and high-dose DEHP groups increased, with much more macrophage infiltrated. The levels of LDL-C, HDL-C, TC in serum and LEP in adipose tissue of rats exposed to 500 mg/kg DEHP were significantly higher than those in the control group (p < 0.05); while the level of ADP in adipose tissue in rats exposed to DEHP was significantly lower (p < 0.05). The levels of IL-1ß and TNF-α in surum and adipose tissue of rats exposed to DEHP were significantly higher than those in the control group (p < 0.05). The mRNA and protein expression levels of CEBP/ß and CD68 in adipose tissue of rats exposed to DEHP were significantly higher than those in the control group. The TC, LEP and ADP Levels of rats were significantly different among different subgroup of IL-1ß and TNF-α, and in high level subgroup, the TC, LEP and ADP Levels were increased. The levels of TC and LEP was increased in high level subgroup of CD68. CONCLUSION: DEHP induced more macrophage infiltrated in adipose tissue of rats, promoted the secretion of IL-1ß, TNF-α and the formation of inflammation, and disturbed the normal lipid metabolism and lead to lipid metabolic disorders. What is more, the levels of inflammation were associated with the lipid levels.


Assuntos
Dietilexilftalato/toxicidade , Inflamação/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/sangue , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adiponectina/sangue , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Peso Corporal , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Inflamação/induzido quimicamente , Interleucina-1beta/sangue , Leptina/sangue , Masculino , Doenças Metabólicas/induzido quimicamente , Ratos , Ratos Wistar , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue
19.
J Gastroenterol Hepatol ; 34(2): 330-345, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30550622

RESUMO

We aimed to review the epidemiologic literature examining lifestyle and metabolic risk factors, and blood-based biomarkers including multi-omics (genomics, proteomics, and metabolomics) and to discuss how these predictive markers can inform early diagnosis of pancreatic ductal adenocarcinoma (PDAC). A search of the PubMed database was conducted in June 2018 to review epidemiologic studies of (i) lifestyle and metabolic risk factors for PDAC, genome-wide association studies, and risk prediction models incorporating these factors and (ii) blood-based biomarkers for PDAC (conventional diagnostic markers, metabolomics, and proteomics). Prospective cohort studies have reported at least 20 possible risk factors for PDAC, including smoking, heavy alcohol drinking, adiposity, diabetes, and pancreatitis, but the relative risks and population attributable fractions of individual risk factors are small (mostly < 10%). High-throughput technologies have continued to yield promising genetic, metabolic, and protein biomarkers in addition to conventional biomarkers such as carbohydrate antigen 19-9. Nonetheless, most studies have utilized a hospital-based case-control design, and the diagnostic accuracy is low in studies that collected pre-diagnostic samples. Risk prediction models incorporating lifestyle and metabolic factors as well as other clinical parameters have shown good discrimination and calibration. Combination of traditional risk factors, genomics, and blood-based biomarkers can help identify high-risk populations and inform clinical decisions. Multi-omics investigations can provide valuable insights into disease etiology, but prospective cohort studies that collect pre-diagnostic samples and validation in independent studies are warranted.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/epidemiologia , Detecção Precoce de Câncer/métodos , Estilo de Vida , Doenças Metabólicas/sangue , Doenças Metabólicas/epidemiologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Feminino , Predisposição Genética para Doença , Genômica , Humanos , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/genética , Metabolômica , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco
20.
Rev Assoc Med Bras (1992) ; 64(12): 1122-1128, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30569989

RESUMO

BACKGROUND: Sleep abnormalities are frequent in patients with endocrine metabolic disorders (EMD) such as arterial hypertension, diabetes and obesity. Adiponectin is a peptide largely secreted by adipocytes and has various properties e.g. anti-inflammatory, antioxidant, antiatherogenic, pro-angiogenic, vasoprotective and insulin-sensitizing. Adiponectin inversely relates to body weight and when its concentration decreases, the resistin concentration increases resulting in greater insulin resistance. OBJECTIVE: The objective of this study is to examine factors influencing adiponectin levels in a population with EMD. METHODS: This was a cross-sectional evaluation of 332 patients (18 to 80y) presenting arterial hypertension, pre-diabetes, diabetes, and/or obesity. Investigation included clinical evaluation of comorbidities, general blood tests and adiponectin measures (ELISA). Chronic sleep deprivation was determined if habitual sleep was <6 hours >4 days/week. RESULTS: Arterial hypertension (78.5%), type-2 diabetes (82.3%), and overweight (45.0%)/obesity (38.8%) were frequent. Patients with type-2 diabetes tended to have more chronic sleep deprivation (p=0.05). Adiponectin levels increased with age and were inversely correlated with sagittal abdominal diameter (p=0.04) and fasting insulin (p=0.001). Chronic sleep deprivation was associated with higher adiponectin concentration [OR=1.34; CI=1.13-1.58; p<0.005] and this was maintained after adjustment for gender, age, body mass index, menopause, arterial hypertension, American Diabetes Association classification and physical exercise levels [OR=1.38; 0=1.14-1.66: p=0.001]. CONCLUSION: In patients with EMD, adiponectin is influenced not only by obesity but also by age and sleep deprivation. The latter finding may be explained by a compensatory effect or a counter regulation to minimize the harmful effects of sleep deprivation.


Assuntos
Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Hipertensão/complicações , Doenças Metabólicas/etiologia , Obesidade/complicações , Privação do Sono/etiologia , Adiponectina/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Humanos , Hipertensão/sangue , Doenças Metabólicas/sangue , Pessoa de Meia-Idade , Fatores de Risco , Privação do Sono/sangue , Adulto Jovem
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