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1.
Sci Rep ; 11(1): 21514, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728695

RESUMO

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.


Assuntos
Adipocinas/sangue , Quimiocinas/sangue , Citocinas/sangue , Lectinas/sangue , Serpinas/sangue , Idoso , Índice de Massa Corporal , Proteína C-Reativa/análise , COVID-19/complicações , COVID-19/metabolismo , COVID-19/patologia , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Proteínas Ligadas por GPI/sangue , Hospitalização , Humanos , Fígado/metabolismo , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , gama-Glutamiltransferase/metabolismo
2.
Nutrients ; 13(10)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34684536

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain. METHODS: In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months' dietary regimens. RESULTS: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet. CONCLUSIONS: Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/dietoterapia , Inflamação/dietoterapia , Inflamação/etiologia , Dor/dietoterapia , Dor/etiologia , Adipocinas/sangue , Adulto , Idoso , Artrite Reumatoide/sangue , Citocinas/sangue , Feminino , Humanos , Inflamação/sangue , Pessoa de Meia-Idade , Dor/sangue , Cooperação do Paciente , Inquéritos e Questionários , Escala Visual Analógica
3.
Nutrients ; 13(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684585

RESUMO

Adipokines and gastrointestinal tract hormones are important metabolic parameters, and both epigenetic factors and differential gene expression patterns may be associated with the alterations in their concentrations in children. The function of the FTO gene (FTO alpha-ketoglutarate dependent dioxygenase) in the regulation of the global metabolic rate is well described, whereas the influence of protooncogene PLAG1 (PLAG1 zinc finger) is still not fully understood. A cross-sectional study on a group of 26 children with various BMI values (15.3-41.7; median 28) was carried out. The aim was to evaluate the dependencies between the level of methylation and expression of aforementioned genes with the concentration of selected gastrointestinal tract hormones and adipokines in children. Expression and methylation were measured in peripheral blood mononuclear DNA by a microarray technique and a restriction enzyme method, respectively. All peptide concentrations were determined using the enzyme immunoassay method. The expression level of both FTO and PLAG1 genes was statistically significantly related to the concentration of adipokines: negatively for apelin and leptin receptor, and positively for leptin. Furthermore, both FTO methylation and expression negatively correlated with the concentration of resistin and visfatin. Cholecystokinin was negatively correlated, whereas fibroblast growth factor 21 positively correlated with methylation and expression of the FTO gene, while FTO and PLAG1 expression was negatively associated with the level of cholecystokinin and glucagon-like peptide-1. The PLAG1 gene expression predicts an increase in leptin and decrease in ghrelin levels. Our results indicate that the FTO gene correlates with the concentration of hormones produced by the adipose tissue and gastrointestinal tract, and PLAG1 gene may be involved in adiposity pathogenesis. However, the exact molecular mechanisms still need to be clarified.


Assuntos
Adipocinas/sangue , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Trato Gastrointestinal/metabolismo , Regulação da Expressão Gênica , Peptídeos/sangue , Adolescente , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Criança , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Modelos Lineares , Masculino , Modelos Biológicos , Estatísticas não Paramétricas
4.
Nutrients ; 13(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34684622

RESUMO

Cornelian cherry (Cornus mas L.) fruits possess potential cardiovascular, lipid-lowering and hypoglycemic bioactivities. The aim of this study is to evaluate the influence of resin-purified cornelian cherry extract rich in iridoids and anthocyanins on several transcription factors, intima/media ratio in aorta and serum parameters, which determine or are valuable indicators of the adverse changes observed in the course of atherosclerosis, cardiovascular disease, and metabolic syndrome. For this purpose, male New Zealand rabbits were fed a diet enriched in 1% cholesterol for 60 days. Additionally, one group received 10 mg/kg b.w. of cornelian cherry extract and the second group 50 mg/kg b.w. of cornelian cherry extract. PPAR-α and PPAR-γ expression in the aorta, LXR-α expression in the liver; cholesterol, triglycerides, adipokines, apolipoproteins, glucose and insulin levels in serum; the intima and media diameter in the thoracic and abdominal aorta were determined. Administration of cornelian cherry extract resulted in an enhancement in the expression of all tested transcription factors, a decrease in triglycerides, leptin and resistin, and an increase in adiponectin levels. In addition, a significant reduction in the I/M ratio was observed for both the thoracic and abdominal aorta. The results we have obtained confirm the potential contribution of cornelian cherry extract to mitigation of the risk of developing and the intensity of symptoms of obesity-related cardiovascular diseases and metabolic disorders such as atherosclerosis or metabolic syndrome.


Assuntos
Antocianinas/farmacologia , Doenças Cardiovasculares/prevenção & controle , Cornus/química , Iridoides/farmacologia , Síndrome Metabólica/prevenção & controle , Extratos Vegetais/farmacologia , Adipocinas/sangue , Animais , Aorta/metabolismo , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/metabolismo , Colesterol na Dieta/efeitos adversos , Humanos , Fígado/metabolismo , Receptores X do Fígado/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , PPAR alfa/metabolismo , PPAR gama/metabolismo , Coelhos , Triglicerídeos/sangue
5.
Nutrients ; 13(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34684629

RESUMO

Melatonin, the hormone of circadian rhythm regulation, is involved in the modulation of mitochondrial activity through its antioxidant and anti-inflammatory properties. Alteration of circadian rhythms such as sleep is related to obesity and metabolic pathogenesis in adulthood, but studies during childhood are scarce. The present study investigated the association of melatonin with metabolic and inflammatory markers in children with (n = 113) and without obesity (n = 117). Melatonin was measured in saliva four and two hours before bedtime, and after one hour of sleep. Cardiometabolic factors, high sensitivity C-reactive protein, immune markers (monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, tumor necrosis α and interferon-γ), leptin and ghrelin were determined. Sleep duration was recorded by a questionnaire. The melatonin level at 1 h after sleep was found to be increased more than twofold in children with obesity (90.16 (57.16-129.16) pg/mL) compared to controls (29.82 (19.05-61.54) pg/mL, p < 0.001) and was related to fat mass (rho = 0.294, p < 0.001); melatonin levels at 1 h after sleep were inversely correlated with high-density lipoprotein cholesterol. Positive correlation was found with apolipoprotein B, adipokines, high sensitivity C-reactive protein, plasminogen activator inhibitor-1 and tumor necrosis factor-α. Shorter sleep duration and earlier waking times were recorded in children with obesity. In conclusion, melatonin in children with obesity appears to be involved in the global metabolic and inflammatory alteration of this condition.


Assuntos
Inflamação/sangue , Melatonina/análise , Obesidade Pediátrica/sangue , Saliva/química , Sono , Adipocinas/sangue , Adolescente , Proteína C-Reativa/análise , Quimiocina CCL2/sangue , Criança , Ritmo Circadiano , Feminino , Grelina/sangue , Humanos , Inflamação/metabolismo , Interferon gama/sangue , Leptina/sangue , Masculino , Obesidade Pediátrica/metabolismo , Inibidor 1 de Ativador de Plasminogênio/sangue , Fator de Necrose Tumoral alfa/sangue
6.
PLoS One ; 16(9): e0257275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34516574

RESUMO

BACKGROUND: Previous studies showed the possible association between obesity, dietary pattern, and depressive symptoms. Due to the lack of enough data to confirm the association of obesity and depression in the Middle East, here, we aimed to explore the possible mediatory role of adipokines Galectin-3, transforming growth factor-beta (TGF-ß), and endothelial plasminogen activator inhibitor (PAI-1) in the association between low carbohydrate diet (LCD) and depressive symptoms. METHODS: A total of 256 women aged 17-56 years old were grouped based on their LCD score. Depression anxiety stress scales-21 (DASS-21) self-administered questionnaire was used to evaluate the three negative emotional states of stress, depressive symptoms, and anxiety. Body composition and dietary intake were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of Galectin-3, TGF-ß, and PAI-1. RESULTS: No significant difference was observed regarding Galectin-3, TGF-ß, and PAI-1 levels between the groups with dissimilar adherence to LCD or the groups with different levels of depressive symptoms (P>0.05). However, there was a negative association between LCD score as a covariant and depressive symptoms as an independent variable (P = 0.02) and remarkably, a regression model linear analysis using Galectin-3, TGF-ß, and PAI-1 as confounding variables indicated the mediatory role of these adipokines in this association (P>0.05). In other words, adipokines eliminated the significance of the relationship between adherence to LCD and depressive symptoms. CONCLUSION: It seems that higher adherence to LCD is probably associated with a lower prevalence of depressive symptoms in obese adults through the mediatory role of adipokines.


Assuntos
Adipocinas/sangue , Depressão/sangue , Dieta com Restrição de Carboidratos , Obesidade/sangue , Sobrepeso/sangue , Adipocinas/metabolismo , Adolescente , Adulto , Antropometria , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/metabolismo , Composição Corporal/fisiologia , Estudos Transversais , Depressão/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Adulto Jovem
7.
Nutrients ; 13(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371941

RESUMO

Insulin-like growth factors (IGFs) and insulin-like growth-factor-binding proteins (IGFBPs) regulate cell proliferation and differentiation and may be of importance in obesity development. The aim of the study was to analyze the expression of chosen IGF-axis genes and the concentration of their protein products in 28 obese children (OB) and 34 healthy control (HC), and their correlation with essential parameters associated with childhood obesity. The gene expression of IGFBP7 was higher, and the expression of IGF2 and IGFBP1 genes was lower in the OB. The expression of IGFBP6 tended to be lower in OB. IGFBP4 concentration was significantly higher, and IGFBP3 tended to be higher in the OB compared to the HC, while IGFBP1, IGFBP2, and IGFBP6 were significantly lower, and IGFBP7 tended to be lower in OB. We found numerous correlations between IGFs and IGFBP concentration and obesity metabolic parameters. IGFBP6 correlated positively with apelin, cholecystokinin, glucagone-like peptide-1, and leptin receptor. These peptides were also significantly lower in obese children in our study. The biological role of decreased levels of IGFBP6 in obese children needs further investigation.


Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like I/análise , Obesidade Pediátrica/sangue , Adipocinas/sangue , Adolescente , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like II/genética , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/genética
8.
Sci Rep ; 11(1): 17001, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417537

RESUMO

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage loss and reduced joint function. OA risk factors are age and obesity. Many adipokines are altered by obesity but also OA although systemic adipokine regulation in OA is not always clear. Therefore, metabolic effects of diet-induced obesity on OA development as well as the influence of obesity and OA progression on systemic vs. local adipokine expression in joints were compared. C57Bl/6-mice fed with HFD (high fat diet) or normal diet prior to destabilization of the medial meniscus (DMM) were sacrificed 4/6/8 weeks after surgery. Sera were evaluated for adiponectin, leptin, visfatin, cytokines. Liver grading and staging for non-alcoholic steatohepatitis (NASH) was performed and crown-like structures (CLS) in adipose tissue measured. OA progression was scored histologically. Adipokine-expressing cells and types were evaluated by immunohistochemistry. Time-dependent changes in DMM-progression were reflected by increased systemic adiponectin levels in DMM especially combined with HFD. While HFD increased serum leptin, DMM reduced systemic leptin significantly. OA scores correlated with bodyweight, leptin and hepatic scoring. Locally, increased numbers of adiponectin- and leptin-producing fibroblasts were observed in damaged menisci but visfatin was not changed. Local adipokine expression was independent from systemic levels, suggesting different mechanisms of action.


Assuntos
Adipocinas/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/metabolismo , Adipocinas/biossíntese , Adipocinas/sangue , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Masculino , Meniscos Tibiais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Osteoartrite do Joelho/sangue
9.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202651

RESUMO

Dieting is a common but often ineffective long-term strategy for preventing weight gain. Similar to humans, adult rats exhibit progressive weight gain. The adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with leptin resistance. Here, we compared the effects of increasing leptin levels in the hypothalamus using gene therapy with conventional caloric restriction on weight gain, food consumption, serum leptin and adiponectin levels, white adipose tissue, marrow adipose tissue, and bone in nine-month-old female Sprague-Dawley rats. Rats (n = 16) were implanted with a cannula in the 3rd ventricle of the hypothalamus and injected with a recombinant adeno-associated virus, encoding the rat gene for leptin (rAAV-Lep), and maintained on standard rat chow for 18 weeks. A second group (n = 15) was calorically-restricted to match the weight of the rAAV-Lep group. Both approaches prevented weight gain, and no differences in bone were detected. However, calorically-restricted rats consumed 15% less food and had lower brown adipose tissue Ucp-1 mRNA expression than rAAV-Lep rats. Additionally, calorically-restricted rats had higher abdominal white adipose tissue mass, higher serum leptin and adiponectin levels, and higher marrow adiposity. Caloric restriction and hypothalamic leptin gene therapy, while equally effective in preventing weight gain, differ in their effects on energy intake, energy expenditure, adipokine levels, and body composition.


Assuntos
Restrição Calórica , Metabolismo Energético , Terapia Genética , Hipotálamo/metabolismo , Leptina/genética , Adipocinas/sangue , Adipocinas/genética , Adipocinas/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo Branco/metabolismo , Adiposidade/genética , Animais , Biomarcadores , Peso Corporal , Medula Óssea/metabolismo , Dependovirus/genética , Ingestão de Energia , Metabolismo Energético/genética , Feminino , Expressão Gênica , Terapia Genética/métodos , Vetores Genéticos , Leptina/metabolismo , Ratos , Transgenes
10.
Nutrients ; 13(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208976

RESUMO

Although bioactive sphingolipids have been shown to regulate cardiometabolic homeostasis and inflammatory signaling pathways in rodents, population-based longitudinal studies of relationships between sphingolipids and onset of metabolic syndrome (MetS) are sparse. We aimed to determine associations of circulating sphingolipids with inflammatory markers, adipokines, and incidence of MetS. Among 1242 Chinese people aged 50-70 years who completed the 6-year resurvey, 76 baseline plasma sphingolipids were quantified by high-throughput liquid chromatography-tandem mass spectrometry. There were 431 incident MetS cases at 6-year revisit. After multivariable adjustment including lifestyle characteristics and BMI, 21 sphingolipids mainly from ceramide and hydroxysphingomyelin subclasses were significantly associated with incident MetS. Meanwhile, the baseline ceramide score was positively associated (RRQ4 versus Q1 = 1.31; 95% CI 1.05, 1.63; ptrend = 0.010) and the hydroxysphingomyelin score was inversely associated (RRQ4 versus Q1 = 0.60; 95% CI 0.45, 0.79; ptrend < 0.001) with incident MetS. When further controlling for clinical lipids, both associations were attenuated but remained significant. Comparing extreme quartiles, RRs (95% CIs) of MetS risk were 1.34 (95% CI 1.06, 1.70; ptrend = 0.010) for ceramide score and 0.71 (95% CI 0.51, 0.97; ptrend = 0.018) for hydroxysphingomyelin score, respectively. Furthermore, a stronger association between ceramide score and incidence of MetS was evidenced in those having higher inflammation levels (RRQ4 versus Q1 1.57; 95% CI 1.16, 2.12; pinteraction = 0.004). Our data suggested that elevated ceramide concentrations were associated with a higher MetS risk, whereas raised hydroxysphingomyelin levels were associated with a lower MetS risk beyond traditional clinical lipids.


Assuntos
Grupo com Ancestrais do Continente Asiático , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Esfingolipídeos/sangue , Adipocinas/sangue , China/epidemiologia , Estudos de Coortes , Análise Fatorial , Feminino , Humanos , Incidência , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Fatores de Risco
11.
BMC Geriatr ; 21(1): 442, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315434

RESUMO

BACKGROUND: Adiponectin and zinc alpha2-glycoprotein (ZAG) are associated with frailty. This study aims to further examine the association of adiponectin with ZAG. METHODS: Outpatients aged 65 years or older with chronic disease followed up in a hospital-based program were recruited for a comprehensive geriatric assessment. We excluded outpatients who were bedridden, residing in a nursing home, with expected life expectancy less than 6 months, or with severe hearing or communication impairment. Plasma ZAG and adiponectin levels were measured. Association between plasma ZAG and adiponectin levels was analyzed by univariate and multivariable linear regression analyses. RESULTS: A total of 189 older adults were enrolled (91 men and 98 women, mean age: 77.2 ± 6.1 years). Log-transformed plasma ZAG level was 1.82 ± 0.11 µg/mL, and it was significantly higher in men than that in women (1.85 ± 0.12 vs 1.79 ± 0.10 µg/mL, P = .0006). Log-transformed plasma adiponectin level was 1.00 ± 0.26 µg/mL, and there was no significant gender difference (P = .195). Overall, plasma ZAG level positively correlated with plasma adiponectin level in the multivariable linear regression analysis (P = .0085). The gender-specific significance, however, was less clear: this relationship was significant in men (P = .0049) but not in women (P = .2072). To be more specific by frailty phenotype components, plasma adiponectin was positively correlated with weight loss (P = .0454) and weakness (P = .0451). CONCLUSIONS: Both of ZAG and adiponectin may be potential frailty biomarkers. Plasma ZAG is an independent factor of plasma adiponectin, especially in older male adults.


Assuntos
Adipocinas/sangue , Adiponectina , Fragilidade , Adiponectina/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Avaliação Geriátrica , Humanos , Masculino , Fatores Sexuais , Perda de Peso
12.
Nutrients ; 13(5)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063273

RESUMO

Excessive adiposity is associated with several metabolic perturbations including disturbances in iron homeostasis. Increased systemic inflammation in obesity stimulates expression of the iron regulatory hormone hepcidin, which can result in a maldistribution of bodily iron, which may be implicated in metabolic dysfunction. This study aimed to investigate the effect of adiposity and any associated inflammation on iron homeostasis and the potential implications of dysregulated iron metabolism on metabolic health. Analyses are based on a subsample from the cross-sectional Irish National Adult Nutrition Survey (2008-2010) (n = 1120). Ferritin status and risk of iron overload were determined based on established WHO ferritin ranges. Participants were classed as having a healthy % body fat or as having overfat or obesity based on age- and gender-specific % body fat ranges as determined by bioelectrical impedance. Biomarkers of iron status were examined in association with measures of body composition, serum adipocytokines and markers of metabolic health. Excessive % body fat was significantly associated with increased serum hepcidin and ferritin and an increased prevalence of severe risk of iron overload amongst males independent of dietary iron intake. Elevated serum ferritin displayed significant positive associations with serum triglycerides and markers of glucose metabolism, with an increased but non-significant presentation of metabolic risk factors amongst participants with overfat and obesity at severe risk of iron overload. Increased adiposity is associated with dysregulations in iron homeostasis, presenting as increased serum hepcidin, elevated serum ferritin and an increased risk of iron overload, with potential implications in impairments in metabolic health.


Assuntos
Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Obesidade/fisiopatologia , Adipocinas/sangue , Adiposidade/fisiologia , Adulto , Biomarcadores/análise , Glicemia/análise , Composição Corporal , Fatores de Risco Cardiometabólico , Estudos Transversais , Feminino , Ferritinas/sangue , Hepcidinas/sangue , Homeostase , Humanos , Inflamação , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/complicações , Prevalência , Fatores Sexuais , Triglicerídeos/sangue
13.
Int J Obes (Lond) ; 45(9): 2126-2131, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34059786

RESUMO

INTRODUCTION: Obesity is commonly reported in COVID-19 patients and is associated with poorer outcomes. It is suggested that leptin could be the missing link between obesity and severe COVID-19. Our study aimed to unravel the link between adipokines, COVID-19 status, immune response, and outcomes in severe pneumonia. METHODS: In this prospective observational single-center study, 63 immunocompetent patients with severe pneumonia (36 non-COVID-19 and 27 COVID-19) were enrolled, most required intensive care. Clinical and biological characteristics (glucose metabolism, plasma adipokines, and cytokine concentrations) and outcomes were compared. RESULTS: At similar baseline severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (p = 0.0049). Plasma concentrations of leptin and adiponectin were respectively positively and negatively correlated with BMI and glucose metabolism (glycemia and insulinemia), but not significantly different between the two groups. Leptin levels were negatively correlated with IL-1ß and IL-6, but the adipokines were not correlated with most other inflammatory mediators, baseline severity (SOFA score), or the duration of mechanical ventilation. CONCLUSION: Adipokine levels were correlated with BMI but not with most inflammatory mediators, severity, or outcomes in severe pneumonia, regardless of the origin. The link between obesity, dysregulated immune response, and life-threatening COVID-19 requires further investigation. CLINICAL TRIAL: ClinicalTrials.gov: NCT03505281.


Assuntos
Adipocinas/imunologia , COVID-19/imunologia , Obesidade/complicações , Adipocinas/sangue , Adiponectina , Idoso , Citocinas , Feminino , Humanos , Imunidade , Leptina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
14.
Sci Rep ; 11(1): 11792, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083628

RESUMO

Zinc-alpha 2-glycoprotein (AZGP1) is a serum protein with postulated functions in metabolism, cancer and cardiovascular disease. We developed new prediction models for mortality or cardiovascular events investigating the predictive potential of serum AZGP1 in a community-based cohort of older adults. We measured AZGP1 (µg/ml) in stored serum samples of 930 individuals of the Berlin Initiative Study, a prospective, population-based cohort of adults aged ≥ 70. We determined the prognostic potential of 20 knowledge-based predictors including AZGP1 for the outcomes of mortality or the composite endpoint of death and cardiovascular events (stroke, myocardial infarction (MI)) using Cox models; their model fit was evaluated with calibration plots, goodness-of-fit tests and c-indices. During median follow-up of 48.3 months, 70 incident strokes, 38 incident MI and 234 deaths occurred. We found no associations or correlations between AZGP1 and other candidate variables. After multivariable Cox regression with backward-selection AZGP1 remained in both models for mortality (HR = 0.44, 95%CI: 0.24-0.80) and for the composite endpoint (HR = 0.43, 95%CI: 0.23-0.82). Within newly built prediction models, we found that increased AZGP1 levels were predictive for lower risk of mortality and the composite endpoint in older adults. AZGP1 as a predictor warrants further validation in older adults.


Assuntos
Adipocinas/sangue , Biomarcadores , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Fatores Etários , Idoso , Variação Biológica Individual , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco
15.
Front Immunol ; 12: 668217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093565

RESUMO

Obesity is the largest risk factor for the development of chronic diseases in industrialized countries. Excessive fat accumulation triggers a state of chronic low-grade inflammation to the detriment of numerous organs. To address this problem, our lab has been examining the anti-inflammatory mechanisms of two human milk oligosaccharides (HMOs), lacto-N-fucopentaose III (LNFPIII) and lacto-N-neotetraose (LNnT). LNFPIII and LNnT are HMOs that differ in structure via presence/absence of an α1,3-linked fucose. We utilize LNFPIII and LNnT in conjugate form, where 10-12 molecules of LNFPIII or LNnT are conjugated to a 40 kDa dextran carrier (P3DEX/NTDEX). Previous studies from our lab have shown that LNFPIII conjugates are anti-inflammatory, act on multiple cell types, and are therapeutic in a wide range of murine inflammatory disease models. The α1,3-linked fucose residue on LNFPIII makes it difficult and more expensive to synthesize. Therefore, we asked if LNnT conjugates induced similar therapeutic effects to LNFPIII. Herein, we compare the therapeutic effects of P3DEX and NTDEX in a model of diet-induced obesity (DIO). Male C57BL/6 mice were placed on a high-fat diet for six weeks and then injected twice per week for eight weeks with 25µg of 40 kDa dextran (DEX; vehicle control), P3DEX, or NTDEX. We found that treatment with P3DEX, but not NTDEX, led to reductions in body weight, adipose tissue (AT) weights, and fasting blood glucose levels. Mice treated with P3DEX also demonstrated improvements in glucose homeostasis and insulin tolerance. Treatment with P3DEX or NTDEX also induced different profiles of serum chemokines, cytokines, adipokines, and incretin hormones, with P3DEX notably reducing circulating levels of leptin and resistin. P3DEX also reduced WAT inflammation and hepatic lipid accumulation, whereas NTDEX seemed to worsen these parameters. These results suggest that the small structural difference between P3DEX and NTDEX has significant effects on the conjugates' therapeutic abilities. Future work will focus on identifying the receptors for these conjugates and delineating the mechanisms by which P3DEX and NTDEX exert their effects.


Assuntos
Amino Açúcares/farmacologia , Anti-Inflamatórios/farmacologia , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Leite Humano , Obesidade/prevenção & controle , Oligossacarídeos/farmacologia , Polissacarídeos/farmacologia , Adipocinas/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Adiposidade/efeitos dos fármacos , Amino Açúcares/síntese química , Animais , Anti-Inflamatórios/síntese química , Fármacos Antiobesidade/síntese química , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Citocinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Leite Humano/química , Estrutura Molecular , Obesidade/sangue , Obesidade/etiologia , Obesidade/fisiopatologia , Oligossacarídeos/síntese química , Polissacarídeos/síntese química , Relação Estrutura-Atividade , Ganho de Peso/efeitos dos fármacos
16.
Int J Biol Macromol ; 183: 2001-2008, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34052271

RESUMO

Major depressive disorder (MDD) is the most common mood disorder, and causes various mental, physical and cognitive symptoms. Clinicians diagnose MDD using multiple interviews and overall impression during the interviews, which makes MDD diagnosis highly subjective. To overcome this, we investigated novel protein biomarker for MDD. Serum from each subject were analyzed using nano liquid chromatography-triple time-of-flight mass spectrometry. We identified two proteins, zinc-alpha-2-glycoprotein (ZA2G) and keratin type II cytoskeletal 1 (K2C1), as final biomarkers. These biomarkers were downregulated during depression (p < 0.05, AUC of ROC >0.7). ZA2G is related to tryptophan metabolism, which is a main serotonin synthesis pathway. K2C1 is involved in the kinin-kallikrein system, which produces bradykinin, an anti-inflammatory mediator in the brain. Our results suggest that the two protein candidates are related to inflammation and that MDD is highly associated with inflammation. Finally, since all subjects in the two groups were taking antidepressants, our results suggest that the identified biomarkers could determine the presence or absence of illness and could be used to monitor therapeutic effects.


Assuntos
Adipocinas/sangue , Biomarcadores/sangue , Transtorno Depressivo Maior/diagnóstico , Queratina-1/sangue , Proteômica/métodos , Regulação para Cima , Adulto , Idoso , Estudos de Casos e Controles , Cromatografia Líquida , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Triptofano/metabolismo
17.
Cancer Causes Control ; 32(8): 871-881, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33999316

RESUMO

OBJECTIVE: Obesity is a known risk factor for colorectal cancer (CRC) and adenoma. Obese individuals have higher circulating concentrations of certain endocrine and immune factors produced by adipocytes thought to partially underlie the association between obesity and colorectal neoplasia. Thus, we evaluated the association of plasma concentrations of adiponectin, leptin, and soluble tumor necrosis factor receptor-2 (sTNFR2) with CRC and adenoma. METHODS: We ascertained 193 CRC cases and 193 matched controls, and 131 colorectal adenoma cases and 131 matched controls who had had an endoscopy nested in the CLUE II cohort of Washington County, MD. Plasma markers were measured using ELISA. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression for quartiles of the plasma markers separately for CRC and adenoma. RESULTS: Adjusting for leptin and adiponectin, sTNFR2 was positively associated with CRC only in men (Q4 vs. Q1: OR = 3.14, 95% CI 1.11-8.86), which was unchanged adjusting for BMI (3.46, 95% CI 1.19-10.06). Leptin and adiponectin were not associated with CRC risk overall or in men or women. Adiponectin, leptin, and sTNFR2 were not associated with adenoma risk overall or in men or women. CONCLUSION: In this study, leptin and adiponectin were not associated with colorectal carcinogenesis and thus do not appear to underlie the association between obesity and colorectal carcinogenesis. sTNFR2, which we measured as a correlate of TNF-α, was positively associated with CRC in men adjusting for BMI, suggesting that TNF-α may influence colorectal carcinogenesis independent of adipocyte production.


Assuntos
Adenoma/sangue , Adipocinas/sangue , Neoplasias Colorretais/diagnóstico , Adiponectina/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Estudos Prospectivos , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue
18.
PLoS One ; 16(5): e0251822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33989346

RESUMO

BACKGROUND: Neuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients. METHODS: Plasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed. RESULTS: Plasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls. CONCLUSION: Our study does not support a role for Nrg4 in the pathophysiology of human NAFLD.


Assuntos
Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Neurregulinas/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adipocinas/sangue , Tecido Adiposo Marrom/metabolismo , Adulto , Índice de Massa Corporal , Progressão da Doença , Feminino , Humanos , Interferon gama/sangue , Interferon gama/genética , Interleucina-6/sangue , Interleucina-6/genética , Gordura Intra-Abdominal/patologia , Lipogênese/genética , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Neurregulinas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética
19.
Obesity (Silver Spring) ; 29(6): 1036-1045, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34029449

RESUMO

OBJECTIVE: This study aimed to examine associations of changes in leptin and adiponectin concentrations from birth to age 12 years with adolescent adiposity and cardiometabolic risk in the Health Outcomes and Measures of Environment (HOME) Study, a prospective birth cohort (Cincinnati, Ohio; N = 166). METHODS: Adiposity and cardiometabolic risk factors were assessed at age 12 years using anthropometry, dual-energy x-ray absorptiometry, and fasting serum biomarkers. Cardiometabolic risk scores were calculated by summing age- and sex- standardized z scores for individual cardiometabolic risk factors. RESULTS: Most serum adipocytokine concentrations at birth were not associated with adiposity or cardiometabolic risk outcomes. Leptin and adiponectin concentrations at age 12 years were associated with all outcomes in the expected direction. Adolescents with increasing (ß: 4.2; 95% CI: 3.2 to 5.2) and stable (ß: 2.2; 95% CI: 1.2 to 3.2) leptin concentrations from birth to age 12 years had higher cardiometabolic risk scores than adolescents with decreasing concentrations (reference group). Adolescents with increasing (e.g., fat mass index = ß: -1.04; 95% CI: -1.27 to -0.80) and stable (ß: 0.66; 95% CI: -0.92 to -0.40) adiponectin/leptin ratios had more favorable adiposity outcomes than adolescents with decreasing ratios. CONCLUSIONS: In this cohort, changes in leptin concentrations and adiponectin/leptin ratios over childhood were associated with adiposity and cardiometabolic risk scores, indicating that adipocytokine concentrations are potential biomarkers for predicting excess adiposity and cardiometabolic risk in adolescence.


Assuntos
Adipocinas/sangue , Adiposidade , Fatores de Risco Cardiometabólico , Adipocinas/análise , Adiposidade/fisiologia , Adolescente , Saúde do Adolescente/estatística & dados numéricos , Fatores Etários , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal/métodos , Ohio/epidemiologia , Obesidade Pediátrica/sangue , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/etiologia , Prognóstico , Fatores de Risco
20.
Eur J Med Res ; 26(1): 38, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931112

RESUMO

BACKGROUND: Multiple organ dysfunction syndrome (MODS) and the consecutive multiple organ failure (MOF) are severe and dreaded complications with a high mortality in multiple trauma patients. The aim of this study was to investigate the potential of the adipokines leptin, resistin, interleukin-17A and interleukin-33 as possible biomarkers in the early posttraumatic inflammatory response and for identifying severely traumatized patients at risk of developing MODS. METHODS: In total, 14 multiple trauma patients with an injury severity score (ISS) ≥ 16 as well as a control group of 14 non-multiple trauma patients were included in this study and blood samples were taken at the time points 0, 6, 24, 48 and 72 h after admission. For the trauma patients, the SIRS and Denver MOF score were determined daily. The quantitative measurement of the plasma concentrations of the adipokines was performed using ELISA. RESULTS: In the statistical analysis, the multiple trauma patients showed statistically significant higher plasma concentrations of leptin, resistin, IL-17A and IL-33 compared to the control group. In addition, there was a statistically significant positive correlation between the concentrations of resistin, IL-17A and IL-33 and the corresponding SIRS scores and between the concentrations of resistin, IL-17A and IL-33 and the corresponding Denver MOF scores. Finally, ROC curve analysis revealed that the adipokines leptin and IL-17A are suitable diagnostic markers for the discrimination between multiple trauma patients with and without MOF. CONCLUSIONS: Leptin and IL-17A could be suitable diagnostic markers to identify severely injured patients with a developing SIRS and MOF earlier, to adjust surgical therapy planning and intensive care.


Assuntos
Adipocinas/sangue , Biomarcadores/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Traumatismo Múltiplo/complicações , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Prognóstico , Curva ROC , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Adulto Jovem
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