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1.
Medicine (Baltimore) ; 99(34): e21882, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846846

RESUMO

Thyroid cancer (TC) is the most well-known endocrine neoplasia as well as a common malignant tumor in the head and neck. Our study was designed to assess the prognostic meaningful of TNFRSF12A expression in TC dependent on data acquired from TCGA and so as to increase further knowledge into the biological pathways involved in TC pathogenesis related TNFRSF12A.Information on gene expression and comparing clinical data were identified and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes indicated by their connection with TNFRSF12A expression.Our study cohort included 370 (73.1%) female and 136 (26.9%) male patients. The scatter plot and paired plot showed the difference of TNFRSF12A expression between normal and tumor samples (P < .01). The univariate analysis suggested that TNFRSF12A-low associated essentially with age (HR: 1.15; 95%CI: 1.08-1.22; P < .01), stage (HR: 2.79; 95%CI: 1.43-5.46; I vs IV; P = .003) and tumor stage (HR: 2.39; 95%CI: 1.08-5.30; P = .031). The GSEA results show that type II diabetes mellitus, pantothenate and CoA biosynthesis, adipocytokine signaling pathway, PPAR signaling pathway, mTOR signaling pathway, insulin signaling pathway, are enriched in TNFRSF12A low expression phenotype.TNFRSF12A expression may be a potential useful prognostic molecular biomarker of bad survival in thyroid cancer, in addition, PPAR signaling pathway, insulin signaling pathway, mTOR signaling pathway may be the key pathway controlled by TNFRSF12A in thyroid cancer. Further experimental ought to be performed to demonstrate the biologic effect of TNFRSF12A.


Assuntos
Transdução de Sinais , Receptor de TWEAK/genética , Neoplasias da Glândula Tireoide/genética , Adipocinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Receptores Ativados por Proliferador de Peroxissomo/genética , Valor Preditivo dos Testes , Prognóstico , Serina-Treonina Quinases TOR/genética , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia
2.
Front Immunol ; 11: 1714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793244

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus leading to a global health outbreak. Despite the high mortality rates from SARS-CoV-1 and Middle-East respiratory syndrome (MERS)-CoV infections, which both sparked the interest of the scientific community, the underlying physiopathology of the SARS-CoV-2 infection, remains partially unclear. SARS-CoV-2 shares similar features with SARS-CoV-1, notably the use of the angiotensin conversion enzyme 2 (ACE2) as a receptor to enter the host cells. However, some features of the SARS-CoV-2 pandemic are unique. In this work, we focus on the association between obesity, metabolic syndrome, and type 2 diabetes on the one hand, and the severity of COVID-19 infection on the other, as it seems greater in these patients. We discuss how adipocyte dysfunction leads to a specific immune environment that predisposes obese patients to respiratory failure during COVID-19. We also hypothesize that an ACE2-cleaved protein, angiotensin 1-7, has a beneficial action on immune deregulation and that its low expression during the SARS-CoV-2 infection could explain the severity of infection. This introduces angiotensin 1-7 as a potential candidate of interest in therapeutic research on CoV infections.


Assuntos
Adipocinas/imunologia , Angiotensina I/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Fragmentos de Peptídeos/imunologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Adipocinas/sangue , Diabetes Mellitus Tipo 2/imunologia , Humanos , Síndrome Metabólica/imunologia , Obesidade/imunologia , Pandemias , Peptidil Dipeptidase A/metabolismo
3.
Proc Natl Acad Sci U S A ; 117(29): 17381-17388, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32632018

RESUMO

Adiponectin (Acrp30) is an adipokine associated with protection from cardiovascular disease, insulin resistance, and inflammation. Although its effects are conventionally attributed to binding Adipor1/2 and T-cadherin, its abundance in circulation, role in ceramide metabolism, and homology to C1q suggest an overlooked role as a lipid-binding protein, possibly generalizable to other C1q/TNF-related proteins (CTRPs) and C1q family members. To investigate this, adiponectin, representative family members, and variants were expressed in Expi293 cells and tested for binding to lipids in liposomes using density centrifugation. Binding to physiological lipids were also analyzed using gradient ultracentrifugation, liquid chromatography-mass spectrometry, and shotgun lipidomics. Interestingly, adiponectin selectively bound several anionic phospholipids and sphingolipids, including phosphatidylserine, ceramide-1-phosphate, glucosylceramide, and sulfatide, via the C1q domain in an oligomerization-dependent fashion. Binding to lipids was observed in liposomes, low-density lipoproteins, cell membranes, and plasma. Other CTRPs and C1q family members (Cbln1, CTRP1, CTRP5, and CTRP13) also bound similar lipids. These findings suggest that adiponectin and CTRPs function not only as hormones, but also as lipid opsonins, as may other C1q family proteins.


Assuntos
Adiponectina/metabolismo , Complemento C1q/metabolismo , Fosfolipídeos/metabolismo , Esfingolipídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adipocinas/metabolismo , Adiponectina/genética , Animais , Ânions , Membrana Celular , LDL-Colesterol , Humanos , Metabolismo dos Lipídeos , Lipidômica , Lipoproteínas/metabolismo , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Opsonizantes/metabolismo , Plasma
4.
Rev Assoc Med Bras (1992) ; 66(5): 596-599, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32638962

RESUMO

AIMS Omentin is an adipokine primarily produced by visceral adipose tissue and its reduced levels have been shown to be associate with worse metabolic outcomes. We aimed to study the effects of preoperative ibuprofen on postoperative omentin levels in rats after surgery. METHODS Forty-eight albino Wistar rats, 6 in each of 8 groups according to the surgical procedure (laparotomy, laparotomy plus ibuprofen (IBU), nephrectomy, nephrectomy plus IBU, hepatectomy, hepatectomy plus IBU, splenectomy and splenectomy plus IBU). The Omentin levels of the groups were postoperatively analyzed. RESULTS The mean omentin was significantly higher in the laparotomy plus IBU group compared to the laparotomy group (p<0.001). Mean Omentin was significantly higher in the hepatectomy plus IBU group compared to the hepatectomy group (p=0.01). Mean Omentin was significantly higher in the nephrectomy plus IBU group compared to the nephrectomy group (p=0.001). CONCLUSION We suggest that preoperative ibuprofen may enhance circulating levels of Omentin, which has beneficial effects in trauma and inflammation settings in subjects that undergo minor or major abdominal surgery.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/sangue , Ibuprofeno/farmacologia , Lectinas/sangue , Adipocinas , Animais , Humanos , Inflamação , Ratos , Ratos Wistar , Esplenectomia
5.
Gen Physiol Biophys ; 39(3): 239-248, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32525817

RESUMO

Colorectal cancer (CRC) is the most common malignant gastrointestinal tumor. Obesity has been confirmed to be closely related to the occurrence of CRC, but the specific mechanism is not clear. This study mainly explored the roles of obesity-related genes, fatty acid synthase (FASN) and zinc-alpha-2-glycoprotein (AZGP1), in CRC. 30 cases of CRC tissues and adjacent normal colorectal tissues were obtained to quantify the levels of FASN and AZGP1 using qRT-PCR and Western blotting. Overexpression-AZGP1, overexpression-FASN and FASN shRNA were transfected into SW480 cells. CCK-8, wound healing and Transwell assays were used to evaluate the roles of FASN and AZGP1 on cell proliferation, migration as well as invasion. Western blot was performed to investigate the expression of MMP-2, MMP-9 and mTOR signaling-related proteins. AZGP1 expression was decreased in CRC tissues, which was negatively correlated with FASN expression. Overexpression-AZGP1 showed a significant inhibitory effect on cell proliferation, invasion and migration via inhibiting MMP-2 and MMP-9 expressions. Furthermore, up-regulation of AZGP1 suppressed the expression of mTOR pathway downstream proteins 4EBP and eIF4E through inhibiting FASN expression. Reintroduction of overexpression-FASN could partially reverse and inhibition of FASN further decrease the anti-tumor effect of AZGP1. AZGP1 suppresses CRC cellular activities by regulating FASN via mTOR pathway, suggesting that AZGP1 and FASN may be the targets for CRC therapy.


Assuntos
Adipocinas/metabolismo , Neoplasias Colorretais/patologia , Ácido Graxo Sintase Tipo I/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica
6.
Rev Assoc Med Bras (1992) ; 66(3): 300-306, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32520149

RESUMO

OBJECTIVES: To compare the serum concentrations of adipokines resistin and chemerin in children and adolescents with eutrophic and overweight and to evaluate their relationship with anthropometric, biochemical, and blood pressure variables. METHODS: a cross-sectional epidemiological study was conducted with 234 students enrolled in public elementary schools in the city of Juiz de Fora / MG. Anthropometric evaluation, biochemistry, and blood pressure measurement were performed. Statistical analyzes included the Student-t or Mann-Whitney tests, Pearson or Spearman correlation, used according to the distribution of the variables, and linear regression analysis, by means of the evaluation of the effect of the independent variables on the serum levels of chemerin and resistin, adjusted for age and sex. For the data analysis, SPSS® software version 21.0 and STATA® version 10.1 were used, assuming a significance level of 5%. RESULTS: the concentrations of chemerin were higher in eutrophic individuals than in those with excess weight (p> 0.05). In contrast, levels of resistin were higher in the young with excess weight than in the eutrophic ones (p <0.05). In the multiple linear regression analysis, the levels of chemerin were associated with the values of resistin, systolic, and diastolic blood pressure. Resistance levels maintained association only with BMI and chemerin values. CONCLUSION: the adipokines analyzed presented a distinct profile in the groups of children and adolescents with eutrophic and overweight.


Assuntos
Adiponectina/sangue , Quimiocinas/sangue , Sobrepeso/sangue , Resistina/sangue , Adipocinas , Adolescente , Antropometria , Criança , Estudos Transversais , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Sobrepeso/complicações , Sobrepeso/metabolismo
7.
Nutr Metab Cardiovasc Dis ; 30(6): 872-888, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32409275

RESUMO

AIMS: This study aimed to summarize earlier studies on the effects of dairy consumption on inflammatory biomarkers in adults and to quantify these effects through meta-analysis. DATA SYNTHESIS: A comprehensive search of all relevant articles, published up to December 2019 indexed in PubMed, ISI (Institute for Scientific Information), EmBase, Scopus, and Google Scholar was done using relevant keywords. Randomized controlled trials (RCTs) that examined the effect of dairy products consumption, compared with low or no dairy intake, on inflammatory biomarkers in adults were included. Overall, 11 RCTs with 663 participants were included in this meta-analysis. We found that high consumption of dairy products, compared with low or no dairy intake, might significantly reduce CRP [weighed mean difference (WMD): -0.24 mg/L; 95% CI, -0.35, -0.14], TNF-α (WMD:- 0.66 pg/mL; 95% CI, -1.23, -0.09), IL-6 (WMD: -0.74 pg/mL; 95% CI, -1.36, -0.12), and MCP concentrations (WMD: -25.58 pg/mL; 95% CI, -50.31, -0.86). However, when the analyses were confined to cross-over trials, no such beneficial effects of dairy intake on inflammation were observed. In addition, high dairy intake might result in increased adiponectin levels (WMD: 2.42 µg/mL; 95% CI, 0.17, 4.66). No significant effect of dairy consumption on serum leptin (WMD: -0.32 ng/mL; 95% CI, -3.30, 2.65), ICAM-1 (WMD: -3.38 ng/ml; 95% CI, -15.57, 8.96) and VCAM-1 (WMD: 3.1 ng/mL; 95% CI, -21.38, 27.58) levels was observed. CONCLUSIONS: In summary, the current meta-analysis indicated that dairy intake might improve several inflammatory biomarkers in adults. In most subgroups without heterogeneity, effects tended to be null. Study design and participants' age were the main sources of heterogeneity. More research, with a particular focus on fat content of dairy foods, is recommended.


Assuntos
Laticínios , Mediadores da Inflamação/sangue , Inflamação/epidemiologia , Adipocinas/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Citocinas/sangue , Laticínios/efeitos adversos , Regulação para Baixo , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
8.
Int J Biometeorol ; 64(9): 1463-1472, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32377931

RESUMO

To investigate the effect of balneotherapy on body mass index, adipokine levels, sleep disturbances, and quality of life in women with morbid obesity. Fifty-four women with morbid obesity were included in the study. The body mass indexes (BMI) and waist/hip ratios (WHR) of the women were calculated. Subcutaneous fat thickness was measured using a *skinfold meter, and the percentage of adipose tissue was calculated. The *Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and the Nottingham Health Profile (NHP) was used to assess quality of life. In addition to routine biochemical tests, leptin, adipokine, visfatin from blood, and cortisol from saliva samples were studied. Participants were given 15 sessions of balneotherapy for 20 min each. After treatment, the laboratory and clinical parameters of the participants were *reevaluated. There was no statistically significant difference of BMI, WHR, and percentage of adipose tissue between before and after treatment measurements (p Ëƒ 0.05).There was a statistically significant improvement in PSQI and NSP scores (p Ë‚ 0.001). The levels of blood glucose, leptin, and visfatin were significantly decreased, and adiponectin was significantly increased after treatment (p = 0.047, p Ë‚ 0.001, p Ë‚ 0.001, and p Ë‚ 0.001, respectively).There was no statistically significant changes in salivary cortisol levels (p = 0.848). Patients with diabetes showed a statistically significant decrease in glucose levels after treatment (p = 0.017).There was a statistically significant decrease in low-density lipoprotein cholesterol levels in patients with dyslipidemia compared with pre-treatment (p = 0.018). Balneotherapy improves sleep and quality of life of women with morbid obesity. After balneotherapy, glucose, leptin, adiponectin, and visfatin levels may change positively.


Assuntos
Balneologia , Obesidade Mórbida , Adipocinas , Adiponectina , Índice de Massa Corporal , Feminino , Humanos , Leptina , Qualidade de Vida
9.
PLoS One ; 15(5): e0233169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407420

RESUMO

In broiler hens, the genetic selection increased susceptibility to metabolic disorders and reproductive dysfunctions. In human ovarian cells, grape seed extracts (GSE) improved steroid production. Here, we investigated the effects of a GSE dietary supplementation on egg production and quality, fertility parameters, Reactive Oxygen Species (ROS) and steroid content in yolk egg associated to plasma adipokines in broiler hens. For this, we designed two in vivo experiments, the first one included three groups of hens: A (control), B and C (supplemented with GSE at 0.5% and 1% of the total diet composition, respectively, since week 4), and the second one used two groups of hens: A (control) and D (supplemented with GSE at 1% of the total diet composition since hatching). We assessed the egg production from 23th to 40th weeks and quality at 33th week. After artificial inseminations, the fertility parameters were calculated. In egg yolk, Reactive Oxygen Species (ROS) level and steroid production were evaluated by Ros-Glo H202 and ELISA assay, respectively. Expression of steroidogenic enzymes and adipokines and their receptors was determined by RT-qPCR in ovarian cells and plasma adipokines (RARRES2, ADIPOQ and NAMPT) were evaluated by specific ELISA assays. The fertility parameters and egg production were unaffected by GSE supplementation whatever the experiment (exp.). However, the rate of double-yolk eggs decreased for all GSE supplemented groups (exp. 1 P <0.01, exp.2, P<0.02). In exp.1, C group eggs were bigger and larger (P<0.0001) and the shell elasticity was higher for both B and C (P<0.0003) as compared to control. In the egg yolk, GSE supplementation in both exp. reduced ROS content and steroidogenesis consistent with a decrease in P450 aromatase and StAR mRNA expression and basal in vitro progesterone secretion in granulosa cells (P<0.001). Interestingly, in both exp. RARRES2 plasma levels were positively correlated while ADIPOQ and NAMPT plasma levels were negatively correlated, with steroids and ROS in yolk (P<0.0001). Taken together, maternal dietary GSE supplementation did not affect egg production and fertility parameters whereas it reduced ROS content and steroidogenesis in yolk egg. Furthermore, it ameliorated egg quality by decreasing the number of double-yolk eggs and by improving the size of normal eggs and the elasticity of the shell. Taken together, our data suggest the possibility of using dietary maternal GSE to improve egg quality.


Assuntos
Galinhas/fisiologia , Suplementos Nutricionais , Fertilidade/efeitos dos fármacos , Extrato de Sementes de Uva/farmacologia , Ovário/metabolismo , Óvulo/metabolismo , Reprodução/efeitos dos fármacos , Esteroides/biossíntese , Adipocinas/sangue , Animais , Galinhas/sangue , Galinhas/genética , Dieta , Gema de Ovo/efeitos dos fármacos , Gema de Ovo/metabolismo , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ovário/efeitos dos fármacos , Oviposição/efeitos dos fármacos , Óvulo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Adipocina/genética , Receptores de Adipocina/metabolismo , Células Tecais/efeitos dos fármacos , Células Tecais/metabolismo
10.
Metabolism ; 108: 154261, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32407726

RESUMO

BACKGROUND: Fibronectin type IIIdomain-containing protein 4 (FNDC4) constitutes a secreted factor showing a high homology in the fibronectin type III and transmembrane domains with the exercise-associated myokine irisin (FNDC5). We sought to evaluate whether FNDC4 mimics the anti-obesity effects of FNDC5/irisin in human adipose tissue. METHODS: Plasma and adipose tissue samples of 78 patients with morbid obesity undergoing bariatric surgery and 26 normal-weight individuals were used in the present study. RESULTS: Plasma FNDC4 was decreased in patients with morbid obesity, related to obesity-associated systemic inflammation and remained unchanged six months after bariatric surgery. Visceral adipose tissue from patients with morbid obesity showed higher expression of FNDC4 and its putative receptor GPR116 regardless of the degree of insulin resistance. FNDC4 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human visceral adipocytes. FNDC4 reduced intracytosolic lipid accumulation and stimulated a brown-like pattern in human adipocytes, as evidenced by an upregulated expression of UCP-1 and the brown/beige adipocyte markers PRDM16, TMEM26 and CD137. Moreover, FNDC4 treatment upregulated mitochondrial DNA content and factors involved in mitochondrial biogenesis (TFAM, NRF1 and NRF2). Human FNDC4-knockdown adipocytes exhibited an increase in lipogenesis and a reduction of brown/beige-specific fat markers as well as factors involved in mitochondrial biogenesis. CONCLUSIONS: Taken together, the novel adipokine FNDC4 reduces lipogenesis and increases fat browning in human visceral adipocytes. The upregulation of FNDC4 in human visceral fat might constitute an attempt to attenuate the adipocyte hypertrophy, inflammation and impaired beige adipogenesis in the obese state.


Assuntos
Adipócitos/metabolismo , Adipocinas/metabolismo , Tecido Adiposo Marrom/metabolismo , Lipogênese/fisiologia , Proteínas/metabolismo , Adipócitos Bege/metabolismo , Células Cultivadas , Estudos Transversais , Feminino , Humanos , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Obesidade/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Proteína Desacopladora 1/metabolismo , Regulação para Cima/fisiologia
11.
PLoS One ; 15(5): e0232483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392256

RESUMO

BACKGROUND: Percutaneous coronary intervention represents the most important treatment modality of coronary artery stenosis. In-stent restenosis (ISR) is still a limitation for the long-term outcome despite the introduction of drug eluting stents. It has been shown that adipokines directly influence vessel wall homeostasis by influencing the function of endothelial cells and arterial smooth muscle cells. Visceral adipose tissue-derived serpin vaspin was recently identified as a member of serine protease inhibitor family and serveral studies could demonstrate a relation to metabolic diseases. The aim of this study was to investigate a role of vaspin in the development of in-stent restenosis in vivo and on migration of smooth muscle cells and endothelial cells in vitro. METHODS: We studied 85 patients with stable coronary artery disease who underwent elective and successful PCI with implatation of drug eluting stents. Blood samples were taken directly before PCI. Vaspin plasma levels were measured by specific ELISA. ISR was evaluated eight months later by coronary angiography. Human coronary artery smooth muscle cells (HCASMC) and human umbilical vein endothelial cells (HUVEC) migration was analyzed by an in-vitro migration assay with different concentrations (0.004ng/mL up to 40ng/mL) of vaspin as well as by an scratch assay. For proliferation an impedance measurement with specialiced E-Plates was performed. RESULTS: During the follow up period, 14 patients developed ISR. Patients with ISR had significantly lower vaspin plasma levels compared to patients without ISR (0.213 ng/ml vs 0.382 ng/ml; p = 0.001). In patients with plasma vaspin levels above 1.35 ng/ml we could not observe any restenosis. There was also a significant correlation of plasma vaspin levels and late lumen loss in the stented coronary segments. Further we could demonstrate that vaspin nearly abolishes serum induced migration of HCASMC (100% vs. 9%; p<0.001) in a biphasic manner but not migration of HUVEC. Proliferation of HCASMC and HUVEC was not modulated by vaspin treatment. CONCLUSION: We were able to show that the adipokine vaspin selectively inhibits human coronary SMC migration in vitro and has no effect on HUVEC migration. Vaspin had no effect on proliferation of HUVEC which is an important process of the healing of the stented vessel. In addition, the occurrence of ISR after PCI with implantation of drug eluting stents was significantly associated with low vaspin plasma levels before intervention. Determination of vaspin plasma levels before PCI might be helpful in the identification of patients with high risk for development of ISR after stent implantation. In addition, the selective effects of vaspin on smooth muscle cell migration could potentially be used to reduce ISR without inhibition of re-endothelialization of the stented segment.


Assuntos
Adipocinas/fisiologia , Reestenose Coronária/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Serpinas/fisiologia , Adipocinas/sangue , Adipocinas/farmacologia , Idoso , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/patologia , Reestenose Coronária/fisiopatologia , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/fisiologia , Serpinas/sangue , Serpinas/farmacologia
12.
Clin Sci (Lond) ; 134(7): 827-851, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32271386

RESUMO

Major shifts in human lifestyle and dietary habits toward sedentary behavior and refined food intake triggered steep increase in the incidence of metabolic disorders including obesity and Type 2 diabetes. Patients with metabolic disease are at a high risk of cardiovascular complications ranging from microvascular dysfunction to cardiometabolic syndromes including heart failure. Despite significant advances in the standards of care for obese and diabetic patients, current therapeutic approaches are not always successful in averting the accompanying cardiovascular deterioration. There is a strong relationship between adipose inflammation seen in metabolic disorders and detrimental changes in cardiovascular structure and function. The particular importance of epicardial and perivascular adipose pools emerged as main modulators of the physiology or pathology of heart and blood vessels. Here, we review the peculiarities of these two fat depots in terms of their origin, function, and pathological changes during metabolic deterioration. We highlight the rationale for pharmacological targeting of the perivascular and epicardial adipose tissue or associated signaling pathways as potential disease modifying approaches in cardiometabolic syndromes.


Assuntos
Adipocinas/antagonistas & inibidores , Tecido Adiposo/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Vasos Sanguíneos/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Inflamação/tratamento farmacológico , Pericárdio/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Adiposidade/efeitos dos fármacos , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Metabolismo Energético/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Terapia de Alvo Molecular , Pericárdio/metabolismo , Pericárdio/patologia , Pericárdio/fisiopatologia , Transdução de Sinais
13.
PLoS One ; 15(4): e0231943, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32330176

RESUMO

Patients diagnosed with polycystic ovary syndrome (PCOS) are at high risk of developing a myriad of endocrinologic and metabolic derailments. Moreover, PCOS is a leading cause of habitual abortion, also known as recurrent pregnancy loss (RPL). Meteorin-like protein (Metrnl) is a newly discovered adipokine with the potential to counteract the metaflammation. This study aimed at determining the associations of serum Metrnl levels with homocysteine, hs-CRP, and some components of metabolic syndrome in PCOS-RPL and infertile PCOS patients.This case-control study was conducted in 120 PCOS patients (60 PCOS-RPL and 60 infertile) and 60 control. Serum hs-CRP and homocysteine were assessed using commercial kits, while adiponectin, Metrnl, FSH, LH, free testosterone and insulin levels were analyzed using ELISA technique. Serum Metrnl levels were found to be lower in PCOS patients when compared to controls (67.98 ± 26.66 vs. 96.47 ± 28.72 pg/mL, P <0.001)). Furthermore, serum adiponectin levels were lower, while free testosterone, fasting insulin, HOMA-IR, homocysteine, and hs-CRP were significantly higher in PCOS group compared to controls. Moreover, serum Metrnl correlated with BMI, adiponectin, and homocysteine in controls, and inversely correlated with FBG, fasting insulin, and HOMA-IR in PCOS group and subgroups. Besides, it inversely correlated with hs-CRP in control, and PCOS group and subgroups. These findings revealed a possible role of Metrnl in the pathogenesis of PCOS and RPL. Nevertheless, there is a necessity for future studies to prove this concept.


Assuntos
Adipocinas/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos
14.
Asian Pac J Cancer Prev ; 21(3): 599-609, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212784

RESUMO

BACKGROUND: Adipokines play an important role in the regulation of inflammation and tumor progression. AIM: Assessment of the possible role of adiponectin, leptin and visfatin in HCV associated hepatocellular carcinoma (HCC). METHODS: patients were classified into 85 patients with HCV associated HCC, 100 patients with chronic hepatitis C viral (HCV) infection compared to 50 normal control (NC) subjects. All subjects included in the study were assessed for HCV infection by seropositive HCV antibodies, as well as HCV RNA by RT-PCR. Serum levels of adiponectin, leptin and visfatin were assessed using enzyme linked immunosorbent assay (ELISA). The data were correlated to the relevant clinic-pathological features of the patients, and the overall survival (OS) rate. RESULTS: There was a significant difference in the serum levels of adiponectin and visfatin among HCC, HCV and NC groups (P<0.001). The serum levels of leptin and alpha fetoprotein (AFP) were significantly higher in HCC group (P<0.001). There was a significant association between the serum level of adiponectin and advanced Child class liver cirrhosis (P=0.03), as well as with poor performance status (ECOG, P=0.02). Serum leptin associated significantly with the number of lesions in the liver (P=0.006), visfatin associated with increased mortality rate (P<0.001). Adiponectin, leptin and visfatin associated significantly with liver cirrhosis in HCV patients (P<0.01). Leptin achieved the highest sensitivity (98.8%). visfatin achieved the highest specificity (100%) and PPV (100%) for detection of HCC. The combination of serum leptin and visfatin for the diagnosis of HCV associated HCC showed sensitivity, specificity, PPV, NPV and accuracy (100%, 96.6%, 93.4%, 100% and 97.4%; respectively). CONCLUSION: Adiponectin, leptin and visfatin have an important role(s) in the pathogenesis of HCV associated HCC. 
.


Assuntos
Adipocinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Hepatite C/complicações , Neoplasias Hepáticas/metabolismo , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue
15.
Cancer Genet ; 243: 7-10, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32179489

RESUMO

BACKGROUND: The genetic basis of diffuse non-Hodgkin's lymphoma (DNHL) is largely unknown now. We conducted a large-scale transcriptome-wide association study (TWAS) of DNHL to identify novel candidates for DNHL. METHODS: The GWAS summary data of DNHL was obtained from the UKBiobank, involving 685 cases and 451,579 controls. TWAS of DNHL was performed using tissue-specific gene expression weights generated from the Genotype-Tissue Expression (GTEx) data. The DNHLTWAS results were further validated by a previous published copy number alterations (CNA) study of DNHL. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes were conducted by the DAVID 6.8. RESULTS: We identified 214 genes with TWAS P value < 0.05 for DNHL, such as MRPL19 (PTWAS = 0.0010), CRCP (PTWAS = 0.0010) and SEMA3C (PTWAS = 0.0010). After further comparing the 214 genes with copy number variations of DNHL patients, we found 1 overlapped gene, BCL10 (PTWAS = 0.0100). We also detected 6 common GO terms shared between gene set enrichment analysis results of TWAS and CNAs, such as cytosol (PTWAS = 0.0003, PCNAs = 4.99 × 10-7) and membrane (PTWAS = 0.0048, PCNAs = 0.0046). The pathway enrichment analysis of TWAS and CNAs detected 3 common pathways, including HIF-1 signaling pathway (PTWAS = 0.0195, PCNAs = 1.96 × 10-5), mTOR signaling pathway (PTWAS = 0.0242, PCNAs = 6.75 × 10-5) and adipocytokine signaling pathway (PTWAS = 0.0392, PCNAs = 0.0103). CONCLUSIONS: Our study identified multiple DNHL associated genes and pathways, providing novel useful information for the pathogenetic studies of DNHL.


Assuntos
Proteína 10 de Linfoma CCL de Células B/genética , Predisposição Genética para Doença , Linfoma não Hodgkin/genética , Transdução de Sinais/genética , Adipocinas/metabolismo , Variações do Número de Cópias de DNA , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Serina-Treonina Quinases TOR/metabolismo
16.
Life Sci ; 250: 117560, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32198054

RESUMO

AIMS: Dietary calcium a common nutrient of our daily diet found to have an anti-obesity effect which may also regulate insulin sensitivity but this effect and the exact mechanism remains unexplored. Therefore, we aimed to study the effect of different types of calcium diet on insulin sensitivity with respect to the changes in the adipokine secretions in high fat diet (HFD) induced obese rats. MAIN METHODS: Healthy male rats were subjected to HFD for 12 weeks to induce obesity and further exposed to a calcium deficient (0.25% Ca) HFD and calcium enriched (1.0% Ca) HFD for another 12 weeks. Thereafter, all rats were sacrificed to collect the blood, liver, adipose tissue and muscle for downstream analysis. KEY FINDINGS: Calcium enriched HFD (1.0% Ca) significantly reduced (p < 0.01) body weight, adiposity index, glucose level, insulin level, HOMA-IR, adipokines (TNF-α, IL-6, MCP-1, Leptin), hepatic lipid accumulation, hepatic macrophage infiltration, adipocyte hypertrophy and significantly increased (p < 0.01) the adiponectin level, in HFD induced obese rats. The down-regulation of the adipokine secretion significantly increased (p < 0.01) the hepatic and muscle glycogen synthase activity and suppressed the hepatic gluconeogenesis activity via activating the insulin receptor-mediated PI3K/AKT/GLUT insulin signaling pathway thereby improving the insulin sensitivity. On the other hand calcium deficient HFD (0.25% Ca) accelerated the risk of insulin resistance (IR) due to its inability to improve insulin sensitivity by activating the associated pathways. SIGNIFICANCE: Calcium enriched HFD (1.0% Ca) reduced the risk of IR by improving the hepatic and muscle insulin sensitivity by restoring adipokine secretion.


Assuntos
Adipócitos/metabolismo , Adipocinas/metabolismo , Cálcio na Dieta/administração & dosagem , Resistência à Insulina , Insulina/metabolismo , Obesidade/metabolismo , Adipocinas/sangue , Tecido Adiposo/metabolismo , Animais , Glicemia/análise , Metabolismo dos Carboidratos , Dieta Hiperlipídica , Teste de Tolerância a Glucose , Fígado/metabolismo , Masculino , Músculos/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais
17.
Chem Biol Interact ; 322: 109059, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171850

RESUMO

Fatty liver is the earliest and most common response of the liver to consumption of excessive alcohol. Steatosis can predispose the fatty liver to develop progressive liver damage. Chief among the many mechanisms involved in development of hepatic steatosis is dysregulation of insulin-mediated adipose tissue metabolism. Particularly, it is the enhanced adipose lipolysis-derived free fatty acids and their delivery to the liver that ultimately results in hepatic steatosis. The adipose-liver axis is modulated by hormones, particularly insulin and adiponectin. In recent studies, we demonstrated that an alcohol-induced increase in serum ghrelin levels impairs insulin secretion from pancreatic ß-cells. The consequent reduction in circulating insulin levels promotes adipose lipolysis and mobilization of fatty acids to the liver to ultimately contribute to hepatic steatosis. Because many tissues, including adipose tissue, express ghrelin receptor we hypothesized that ghrelin may directly affect energy metabolism in adipocytes. We have exciting new preliminary data which shows that treatment of premature 3T3-L1 adipocytes with ghrelin impairs adipocyte differentiation and inhibits lipid accumulation in the tissue designed to store energy in the form of fat. We further observed that ghrelin treatment of differentiated adipocytes significantly inhibited secretion of adiponectin, a hepatoprotective hormone that reduces lipid synthesis and promotes lipid oxidation. These results were corroborated by our observations of a significant increase in serum adiponectin levels in ethanol-fed rats treated with a ghrelin receptor antagonist verses the un-treated ethanol-fed rats. Interestingly, in adipocytes, ghrelin also increases secretion of interleukin-6 (IL-6) and CCL2 (chemokine [C-C motif] ligand 2), cytokines which promote hepatic inflammation and progression of liver disease. To summarize, the alcohol-induced increase in serum ghrelin levels dysregulates adipose-liver interaction and promotes hepatic steatosis by increasing the free fatty acid released from adipose for hepatic uptake, and by altering adiponectin and cytokine secretion. Taken together, our data indicates that targeting the activity of ghrelin may be a powerful treatment strategy.


Assuntos
Tecido Adiposo/metabolismo , Fígado Gorduroso Alcoólico/patologia , Grelina/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Células 3T3-L1 , Adipocinas/metabolismo , Adiponectina/sangue , Adiponectina/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Etanol/farmacologia , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/veterinária , Interleucina-6/metabolismo , Masculino , Camundongos , Oligopeptídeos/farmacologia , PPAR gama/metabolismo , Ratos , Ratos Wistar
18.
Wiad Lek ; 73(1): 180-187, 2020.
Artigo em Polonês | MEDLINE | ID: mdl-32124831

RESUMO

Prostate cancer is the most commonly diagnosed cancer among men in the world and in Poland it is the second cause of death in men suffering from cancer. Recent evidence suggests that obesity is associated with prostate cancer. Increased BMI correlates with aggressive disease and with higher risk of recurrence and mortality in prostate cancer patients. Obesity can promote the progression of prostate cancer through endocrine disturbances, mainly in sex steroids, through chronic inflammation resulting in altered production of adipokines, peripheral insulin resistance with hyperinsulinemia and oxidative stress. Diagnosis of metabolic syndrome can be used in the global assessment of prognosis in patients with prostate cancer. The aim of the paper is to present current state of knowledge about connections between obesity, metabolic syndrome, sex steroids and adipokines in men with prostate cancer.


Assuntos
Síndrome Metabólica , Obesidade/complicações , Neoplasias da Próstata , Adipocinas , Humanos , Masculino , Síndrome Metabólica/complicações , Recidiva Local de Neoplasia , Polônia , Neoplasias da Próstata/etiologia
19.
PLoS One ; 15(3): e0229765, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130282

RESUMO

AIM: To evaluate the serum concentrations of inflammatory mediators in patients with type 2 diabetes mellitus (T2DM) with or without renal alteration (RA) function. METHODS: Serum samples from 76 patients with T2DM and 24 healthy individuals were selected. Patients with T2DM were divided into two groups according to eGFR (> or < 60mL/min/1.73m2). Cytokines, chemokines and adipokines levels were evaluated using the Multiplex immunoassay and ELISA. RESULTS: TNFR1 and leptin were higher in the T2DM group with RA than in the T2DM group without RA and control group. All patients with T2DM showed increased resistin, IL-8, and MIP-1α compared to the control group. Adiponectin were higher and IL-4 decreased in the T2DM group with RA compared to the control group. eGFR positively correlated with IL-4 and negatively with TNFR1, TNFR2, and leptin in patients with T2DM. In the T2DM group with RA, eGFR was negatively correlated with TNFR1 and resistin. TNFR1 was positively correlated with resistin and leptin, as well as resistin with IL-8 and leptin. CONCLUSION: Increased levels of TNFR1, adipokines, chemokines and decrease of IL-4 play important role in the inflammatory process developed in T2DM and decreased renal function. We also suggest that TNFR1 is a strong predictor of renal dysfunction in patients with T2DM.


Assuntos
Adipocinas/sangue , Quimiocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Interleucinas/sangue , Rim/fisiopatologia , Adulto , Biomarcadores/sangue , Antígenos CD40/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Environ Sci Pollut Res Int ; 27(14): 16231-16245, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32124283

RESUMO

BPA, one of the environmental endocrine disruptors, and fructose, reason of liver steatosis which is frequently encountered in the daily diet, contribute to the formation of metabolic syndrome (MetS). This study examines the possible effects of concurrent fructose and BPA administration on MetS and determines the effects of melatonin on this process. In the seven identified groups, a total of forty-two adult male Sprague Dawley rats were treated by following fructose, BPA, and melatonin amounts, separately and together: group 1 (control), group 2 (10% aqueous fructose), group 3 (25 mg/kg BPA), group 4 (10% fructose + 25 mg/kg BPA), group 5 (10% fructose + 20 mg/kg melatonin), group 6 (25 mg/kg BPA + 20 mg/kg melatonin), and group 7 (10% fructose + 25 mg/kg BPA + 20 mg/kg melatonin). At the end of 60 days, histochemical, immunohistochemical, and biochemical procedures were performed on liver tissue. As a result, it was seen that BPA and fructose + BPA induced morphological alteration and inflammation and increased intracellular lipid quantity and amount of collagen and reticular fibers. The percentage of apoptotic liver cells stained by annexin V-FITC/PI was lower in group 7 compared to the group 4 (p < 0,001) and also in group 6 compared to the group 3 (p = 0.014). Both BPA and fructose application caused an increase in lipid peroxidation level due to the increase of oxidative stress. Application of melatonin induced antioxidant enzyme activity and reduced lipid peroxidation level. Our results indicate that fructose and BPA administration triggered the formation of MetS, whereas melatonin healed these variations, although not entirely.


Assuntos
Melatonina , Adipocinas , Animais , Antioxidantes , Compostos Benzidrílicos , Frutose , Fígado , Masculino , Estresse Oxidativo , Fenóis , Ratos , Ratos Sprague-Dawley
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