Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 570
Filtrar
1.
J Transl Med ; 20(1): 504, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329504

RESUMO

BACKGROUND: Periodontitis is a major inflammatory disease of the oral mucosa that is not limited to the oral cavity but also has systemic consequences. Although the importance of chronic periodontitis has been emphasized, the systemic immune response induced by periodontitis and its therapeutic effects remain elusive. Here, we report the transcriptomes of peripheral blood mononuclear cells (PBMCs) from patients with periodontitis. METHODS: Using single-cell RNA sequencing, we profiled PBMCs from healthy controls and paired pre- and post-treatment patients with periodontitis. We extracted differentially expressed genes and biological pathways for each cell type and calculated activity scores reflecting cellular characteristics. Intercellular crosstalk was classified into therapy-responsive and -nonresponsive pathways. RESULTS: We analyzed pan-cellular differentially expressed genes caused by periodontitis and found that most cell types showed a significant increase in CRIP1, which was further supported by the increased levels of plasma CRIP1 observed in patients with periodontitis. In addition, activated cell type-specific ligand-receptor interactions, including the BTLA, IFN-γ, and RESISTIN pathways, were prominent in patients with periodontitis. Both the BTLA and IFN-γ pathways returned to similar levels in healthy controls after periodontal therapy, whereas the RESISTIN pathway was still activated even after therapy. CONCLUSION: These data collectively provide insights into the transcriptome changes and molecular interactions that are responsive to periodontal treatment. We identified periodontitis-specific systemic inflammatory indicators and suggest unresolved signals of non-surgical therapy as future therapeutic targets.


Assuntos
Periodontite Crônica , Resistina , Humanos , Resistina/metabolismo , Leucócitos Mononucleares/metabolismo , Periodontite Crônica/genética , Periodontite Crônica/terapia , Análise de Sequência de RNA
2.
Nutrients ; 14(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36296907

RESUMO

BACKGROUND AND AIMS: Metabolic Associated Fatty Liver Disease (MAFLD) encompasses a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH). Here, we investigated the hepatoprotective role of Moringa oleifera aqueous extract on hepatic miRNAs, genes and protein expression, as well as histological and biochemical parameters in an experimental model of NASH. METHODS: Male C57BL/6J mice were fed with a high fat diet (HFD, 60% lipids, 42 gr/L sugar in water) for 16 weeks. Moringa extract was administered via gavage during the final 8 weeks. Insulin Tolerance Test (ITT) and HOMA-IR were calculated. Serum levels of insulin, resistin, leptin and PAI-1 and hepatic expression of miR-21a-5p, miR-103-3p, miR-122-5p, miR-34a-5p and SIRT1, AMPKα and SREBP1c protein were evaluated. Alpha-SMA immunohistochemistry and hematoxylin-eosin, Masson's trichrome and sirius red staining were made. Hepatic transcriptome was analyzed using microarrays. RESULTS: Animals treated with Moringa extract improved ITT and decreased SREBP1c hepatic protein, while SIRT1 increased. Hepatic expression of miR-21a-5p, miR-103-3p and miR-122-5p, miR34a-5p was downregulated. Hepatic histologic analysis showed in Moringa group (HF + MO) a significant decrease in inflammatory nodules, macro steatosis, fibrosis, collagen and αSMA reactivity. Analysis of hepatic transcriptome showed down expression of mRNAs implicated in DNA response to damage, endoplasmic reticulum stress, lipid biosynthesis and insulin resistance. Moringa reduced insulin resistance, de novo lipogenesis, hepatic inflammation and ER stress. CONCLUSIONS: Moringa prevented progression of liver damage in a model of NASH and improved biochemical, histological and hepatic expression of genes and miRNAs implicated in MAFLD/NASH development.


Assuntos
Resistência à Insulina , MicroRNAs , Moringa oleifera , Hepatopatia Gordurosa não Alcoólica , Extratos Vegetais , Animais , Masculino , Camundongos , Dieta Hiperlipídica/efeitos adversos , Epigênese Genética , Insulina/metabolismo , Leptina , Lipídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Moringa oleifera/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Resistina/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Extratos Vegetais/farmacologia
3.
Turkiye Parazitol Derg ; 46(3): 195-200, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094120

RESUMO

Objective: Cystic echinococcosis (CE) is one of the most common zoonotic diseases worldwide. Diagnosis of CE is predominantly based on imaging techniques and serological tests are used in cases of non-characteristic imaging findings as diagnostic reference. However, serological test results cannot be completely reliable as they are affected by multi-factors. P-selectin and resistin are inflammatory markers that are altered during the acute stages of infection. In this purpose, inflammatory markers as P-selectin and resistin have been investigated for a potential diagnostic reference for CE diagnosis. Methods: A total of 60 patients who were diagnosed with CE and twenty-five healthy individuals were included in this study. Blood samples were obtained from all participants. Obtained sera were evaluated using the P-selectin and resistin ELISA kits for protein levels. Additionally, the relative expression of SELP (P-selectin) and RETN (resistin) genes were determined using the comparative CT (ΔΔCT) method between groups as CE patients with active and inactive cysts, CE patients and healthy controls. Results: SELP (13.9-fold change, p<0.05) and RETN (8.1-fold change, p<0.05) were differentially expressed in CE patients compared in the control group. Whereas resistin protein levels were significantly higher in CE patients than the healthy controls (p<0.001), the difference in P-selectin protein levels was not significant (p>0.05). There was no difference between active and inactive CE patients in terms of P-selectin and resistin in gene and protein levels (p>0.05). Conclusion: Although there was no difference between the active and inactive CE patients, the good differentiation between the healthy controls and the CE patients suggested that resistin is a potential inflammatory diagnostic reference.


Assuntos
Equinococose , Resistina , Equinococose/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Selectina-P , Resistina/genética , Resistina/metabolismo
4.
Int J Mol Sci ; 23(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36142272

RESUMO

The aim of this study was to evaluate the levels of ten energy metabolism factors: C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1 (total), resistin, and visfatin, and to determine the expression of GLP1R receptors, CD10, CD26 proteases, and pro-inflammatory marker CD86 by macrophages in the peritoneal fluid (PF) in patients with endometriosis. The study included 54 women with endometriosis and a control group of 30 women with uterine myoma without signs of endometriosis. The levels of factors in PF were assessed by a multiplex method. Expression of GLP1R receptors, CD10, CD26 proteases, and CD86 by macrophages was evaluated using flow cytometry. It was found that in women with endometriosis, the concentrations of ghrelin, GLP-1, glucagon, and visfatin in PF were reduced (p = 0.007, p = 0.009, p = 0.002, p = 0.008, respectively). At the same time, there was a noted increase in the CD10 protease expression by peritoneal macrophages (p = 0.044). Correlation analysis showed a positive correlation of ghrelin and GLP-1 levels with CD86 macrophage expression (p = 0.044, p = 0.022, respectively) in the study group; a positive correlation was also found between the levels of GLP-1, glucagon, and visfatin with CD26 macrophage expression (p = 0.041, p = 0.048, p = 0.015, respectively) in PF. No correlations were found in the control group. These results indicate that a decrease in the levels of ghrelin, GLP-1, glucagon, and visfatin in PF may contribute to endometriosis development through their impact on the expression of pro-inflammatory markers of PF macrophages.


Assuntos
Endometriose , Glucagon , Líquido Ascítico/metabolismo , Biomarcadores/metabolismo , Peptídeo C/metabolismo , Dipeptidil Peptidase 4/metabolismo , Endometriose/metabolismo , Feminino , Grelina/metabolismo , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Leptina/metabolismo , Macrófagos/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Peptídeo Hidrolases/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Resistina/metabolismo
5.
Sci Rep ; 12(1): 15437, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104403

RESUMO

The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy.


Assuntos
Neoplasias da Mama , Resistina , Tecido Adiposo/metabolismo , Animais , Neoplasias da Mama/patologia , Quimiocina CXCL5/metabolismo , Técnicas de Cocultura , Feminino , Humanos , Camundongos , Resistina/metabolismo , Células-Tronco , Microambiente Tumoral
6.
Sci Rep ; 12(1): 15313, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097281

RESUMO

Obesity is a significant risk factor for the development of knee osteoarthritis (KOA). However, the precise molecular mechanisms linking obesity to OA remain unclear. In the present study, we investigated the effect of short-term high-fat diet (HFD) on the development of OA and the possible role of the adipokine resistin and autophagy-related genes in mediating this effect. Thirty adult male Wistar rats were equally divided into 2 groups: control and obese groups. Body mass index (BMI), levels of lipid profile, glucose, insulin and HOMA-IR index were significantly higher in the obese group compared with control. Our results revealed significantly higher serum and cartilage resistin levels with a significant increase in the mRNA expressions of toll-like receptor 4 (TLR4), matrix metalloproteinase-9 (MMP-9) and interleukin-1ß (IL-1ß) as well as protein levels of IL-1ß, matrix metalloproteinase-13 (MMP-13), ADAMTS 5 (aggrecanase-2) and caspase-3 in the cartilage of obese rats. The HFD induced a significant upregulation of autophagy related 5 (ATG5), beclin-1 and light chain 3 (LC3) mRNA expressions and a significant downregulation of mammalian target of rapamycin (mTOR) expression in cartilage. The protein levels of cartilage ATG5 were also significantly elevated in HFD-fed group. In conclusion, we suggested that increased levels of resistin and expression of autophagy-related genes may contribute in part, to OA development in HFD-fed rats. This provides a novel insight into the early molecular changes in the cartilage associated with obesity.


Assuntos
Dieta Hiperlipídica , Resistina , Animais , Autofagia/genética , Cartilagem/metabolismo , Dieta Hiperlipídica/efeitos adversos , Masculino , Mamíferos/metabolismo , Obesidade/complicações , RNA Mensageiro/genética , Ratos , Ratos Wistar , Resistina/genética , Resistina/metabolismo
7.
Int J Mol Sci ; 23(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35955609

RESUMO

Endosome-localized Toll-like receptors (TLRs) 3 and 9 are expressed and functionally active in adipocytes. The functionality and role of TLR7 in adipocyte biology and innate immunity of adipose tissue (AT) is poorly characterized. We analyzed TLR7 mRNA and protein expression in murine 3T3-L1 and primary adipocytes, in co-cultures of 3T3-L1 adipocytes with murine J774A.1 monocytes and in human AT. The effects of TLR7 agonists imiquimod (IMQ) and cell-free nucleic acids (cfDNA) on adipokine concentration in cell-culture supernatants and gene expression profile were investigated. We found that TLR7 expression is strongly induced during adipocyte differentiation. TLR7 gene expression in adipocytes and AT stroma-vascular cells (SVC) seems to be independent of TLR9. IMQ downregulates resistin concentration in adipocyte cell-culture supernatants and modulates gene expression of glucose transporter Glut4. Adipocyte-derived cfDNA reduces adiponectin and resistin in cell-culture supernatants and potentially inhibits Glut4 gene expression. The responsiveness of 3T3-L1 adipocytes to imiquimod is preserved in co-culture with J774A.1 monocytes. Obesity-related, adipocyte-derived cfDNA engages adipocytic pattern recognition receptors (PRRs), modulating AT immune and metabolic homeostasis during adipose inflammation.


Assuntos
Ácidos Nucleicos Livres , Resistina , Células 3T3-L1 , Adipócitos/metabolismo , Adjuvantes Imunológicos/farmacologia , Animais , Diferenciação Celular/genética , Ácidos Nucleicos Livres/metabolismo , Humanos , Imiquimode/farmacologia , Camundongos , Resistina/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo
8.
Res Vet Sci ; 150: 189-194, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-35842950

RESUMO

A number of alterations have been identified in lipid metabolism within adipose tissue and liver in obesity. Less is known about the capacity of skeletal muscle for the metabolism of fatty acids in obesity-related insulin resistance, though it is evident that dry cow muscles may contain increased triglyceride content. The current study was therefore undertaken to evaluate the skeletal muscle expression of proteins of the fatty acid metabolism in dry cows with different body condition scores (BCS). Sixteen Holstein-Friesian close-up cows were divided into 2 equal groups based on their BCS as optimal (3.25 ≤ BCS ≤ 3.5) and high (4.0 ≤ BCS ≤ 4.25). Blood samples collection and skeletal muscle biopsies were carried out at day 10 before calving. Blood serum was assayed for concentration of resistin using a bovine specific ELISA. Protein expression of insulin receptor beta subunit (IRß), glucose transporter 4 (GLUT4), fatty acid translocase (FAT/CD36), fatty acid transporter 1 (FATP1), carnitine palmitoyltransferase 1 (CPT1), AMP-acitvated protein kinase (AMPK) and lipin 1 were analyzed in semitendinosus muscle by immunoblot. Resistin differed non-significantly between high-BCS and optimal-BCS cows. Insulin-resistant lipid metabolism in obese cows was paralleled with increased skeletal muscle expression of lipin 1 and GLUT4, and decreased expression of IRß and FATP1. These data suggest that in obesity-related insulin resistance, metabolic capacity in dry cow skeletal muscles appears to be organized towards the synthesis of signaling intermediates rather than fatty acids oxidation and that altered fatty acid uptake does not contribute to this disposition.


Assuntos
Doenças dos Bovinos , Resistência à Insulina , Animais , Antígenos CD36/metabolismo , Bovinos , Doenças dos Bovinos/metabolismo , Ácidos Graxos/metabolismo , Feminino , Insulina , Resistência à Insulina/fisiologia , Lactação/fisiologia , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Obesidade/veterinária , Compostos Orgânicos , Resistina/metabolismo
9.
Psychoneuroendocrinology ; 144: 105862, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35835020

RESUMO

Weight gain is the one of the most important factors which increases global burden of psychiatric disorder. Second-generation antipsychotics, olanzapine (Olz) and valproic acid (Vpa) in particular, are held responsible for weight gain. However, it is still uncertain how these drugs cause this. Thus, the rats selected for the experiment were randomly divided into 3 groups. The 1st group received only 0.5 ml saline solution intraperitoneally (n = 20, control group); the second group was given 200 mg / kg Vpa intraperitoneally (n = 20, Vpa group) and 2 mg / kg Olz was given intraperitoneally to the 3rd group (n = 20, Olz group) between 8 and 10 am for 30 days. We examined serum leptin, adiponectin, resistin, TNF-α, IL-6, ghrelin level and, the amount of ghrelin secreting cells in the stomach and growth hormone secretagogue receptor-1a (GHSR-1a, ghrelin receptor) expression in the hypothalamus. The hypothalamic GHS-1a receptor index was significantly higher in the Olz group compared with the control group and Vpa group (p = 0.036 and p = 0.016 respectively). Ghrelin immune positive cell index in stomach was statistically significantly lower in the Vpa group compared with the control and Olz groups (p = 0.028 and p = 0.013 respectively) There was no difference between the groups in terms of serum leptin, resistin, IL-6 and ghrelin levels. In the Vpa group, a statistically significant increase was found in serum adiponectin level compared with both the control group and the Olz group (p = 0009 and p = 0024 respectively) and, significant decrease was found in serum TNF-α level compared to Olz group (p = 0007). In conclusion, we found that the main cause of weight gain in Olz use was the increase in the number of hypothalamic ghrelin receptors. Investigating the mechanism by which Olz increases the number of ghrelin receptors may help to develop effective treatment strategies in preventing obesity in psychiatric patients.


Assuntos
Grelina , Receptores de Grelina , Adiponectina/metabolismo , Animais , Grelina/metabolismo , Grelina/farmacologia , Hipotálamo/metabolismo , Interleucina-6/metabolismo , Leptina/metabolismo , Olanzapina/farmacologia , Ratos , Receptores de Grelina/metabolismo , Resistina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácido Valproico/farmacologia , Aumento de Peso
10.
Cell Stress Chaperones ; 27(5): 499-511, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35779187

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a major health concern. Endoplasmic reticulum (ER) stress, inflammation, and metabolic dysfunctions may be targeted to prevent the progress of nonalcoholic fatty liver disease. Sulforaphane (SFN), a sulfur-containing compound that is abundant in broccoli florets, seeds, and sprouts, has been reported to have beneficial effects on attenuating metabolic diseases. In light of this, the present study was designed to elucidate the mechanisms by which SFN ameliorated ER stress, inflammation, lipid metabolism, and insulin resistance - induced by a high-fat diet and ionizing radiation (IR) in rats. In our study, the rats were randomly divided into five groups: control, HFD, HFD + SFN, HFD + IR, and HFD + IR + SFN groups. After the last administration of SFN, liver and blood samples were taken. As a result, the lipid profile, liver enzymes, glucose, insulin, IL-1ß, adipokines (leptin and resistin), and PI3K/AKT protein levels, as well as the mRNA gene expression of ER stress markers (IRE-1, sXBP-1, PERK, ATF4, and CHOP), fatty acid synthase (FAS), peroxisome proliferator-activated receptor-α (PPAR-α). Interestingly, SFN treatment modulated the levels of proinflammatory cytokine including IL-1ß, metabolic indices (lipid profile, glucose, insulin, and adipokines), and ER stress markers in HFD and HFD + IR groups. SFN also increases the expression of PPAR-α and AMPK genes in the livers of HFD and HFD + IR groups. Meanwhile, the gene expression of FAS and CHOP was significantly attenuated in the SFN-treated groups. Our results clearly show that SFN inhibits liver toxicity induced by HFD and IR by ameliorating the ER stress events in the liver tissue through the upregulation of AMPK and PPAR-α accompanied by downregulation of FAS and CHOP gene expression.


Assuntos
Estresse do Retículo Endoplasmático , Insulinas , Isotiocianatos , Hepatopatia Gordurosa não Alcoólica , Sulfóxidos , Proteínas Quinases Ativadas por AMP/genética , Animais , Citocinas/metabolismo , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/farmacologia , Glucose/metabolismo , Insulinas/genética , Insulinas/metabolismo , Insulinas/farmacologia , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Leptina , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Ratos , Resistina/genética , Resistina/metabolismo , Resistina/farmacologia , Sulfóxidos/farmacologia , Sulfóxidos/uso terapêutico , Regulação para Cima
11.
Mol Med Rep ; 26(2)2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35730599

RESUMO

Cerulein­induced pancreatitis resembles human acute pancreatitis in terms of pathological events, such as enzymatic activation and inflammatory cell infiltration in the pancreas. Cerulein is a cholecystokinin analog that increases levels of reactive oxygen species (ROS) and interleukin­6 (IL­6) expression level in pancreatic acinar cells. Serum levels of resistin, which is secreted from adipocytes, are reportedly higher in patients with acute pancreatitis than in healthy individuals. Previously, it was shown that the adipokine resistin can aggravate the cerulein­induced increase in ROS levels and IL­6 expression level in pancreatic acinar cells. Peroxisome proliferator­activated receptor­gamma (PPAR­Î³) is a key regulator of the transcription and expression of antioxidant enzymes, including heme oxygenase 1 (HO­1) and catalase. α­lipoic acid, a naturally occurring dithiol antioxidant, can prevent cerulein­induced pancreatic damage in rats. In the present study, it was aimed to investigate whether α­lipoic acid can attenuate the cerulein/resistin­induced increase in IL­6 expression and ROS levels via PPAR­Î³ activation in pancreatic acinar AR42J cells. The anti­inflammatory mechanism of α­lipoic acid was determined using reverse transcription­quantitative PCR, western blot analysis, enzyme­linked immunosorbent assay, immunofluorescence staining and fluorometry. Treatment with cerulein and resistin increased ROS levels and IL­6 expression level, which were inhibited by α­lipoic acid in pancreatic acinar cells. α­lipoic acid increased the nuclear translocation and expression level of PPAR­Î³ and the expression levels of its target genes: HO­1 and catalase. The PPAR­Î³ antagonist GW9662 and HO­1 inhibitor zinc protoporphyrin reversed the inhibitory effect of α­lipoic acid on cerulein/resistin­induced increase in ROS and IL­6 levels. In conclusion, α­lipoic acid inhibits the cerulein/resistin­induced increase in ROS production and IL­6 expression levels by activating PPAR­Î³ and inducing the expression of HO­1 and catalase in pancreatic acinar cells.


Assuntos
Pancreatite , Ácido Tióctico , Células Acinares/metabolismo , Doença Aguda , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase/metabolismo , Ceruletídeo/toxicidade , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Pâncreas/patologia , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Resistina/metabolismo , Ácido Tióctico/farmacologia
12.
Biomolecules ; 12(6)2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35740864

RESUMO

Saturated fatty acids (SFAs) are considered to be detrimental to human health. One of the SFAs, myristic acid (MA), is known to exert a hypercholesterolemic effect in mice as well as humans. However, its effects on altering adipose tissue (AT) inflammation and systemic insulin resistance (IR) in obesity are still unclear. Here, we sought to determine the effects of a high fat (HF) diet supplemented with MA on obesity-associated metabolic disorders in mice. Wild-type C57BL/6 mice were fed a HF diet in the presence or absence of 3% MA for 12 weeks. Plasma lipids, plasma adipokines, AT inflammation, systemic IR, glucose homeostasis, and hepatic steatosis were assessed. The body weight and visceral adipose tissue (VAT) mass were significantly higher in mice receiving the HF+MA diet compared to HF diet-fed controls. Plasma total cholesterol levels were marginally increased in HF+MA-fed mice compared to controls. Fasting blood glucose was comparable between HF and HF+MA-fed mice. Interestingly, the plasma insulin and HOMA-IR index, a measure of insulin resistance, were significantly higher in HF+MA-fed mice compared to HF controls. Macrophage and inflammatory markers were significantly elevated in the AT and AT-derived stromal vascular cells upon MA feeding. Moreover, the level of circulating resistin, an adipokine promoting insulin resistance, was significantly higher in HF+MA-fed mice compared with HF controls. The insulin tolerance test revealed that the IR was higher in mice receiving the MA supplementation compared to HF controls. Moreover, the glucose tolerance test showed impairment in systemic glucose homeostasis in MA-fed mice. Analyses of liver samples showed a trend towards an increase in liver TG upon MA feeding. However, markers of oxidative stress and inflammation were reduced in the liver of mice fed an MA diet compared to controls. Taken together, our data suggest that chronic administration of MA in diet exacerbates obesity-associated insulin resistance and this effect is mediated in part, via increased AT inflammation and increased secretion of resistin.


Assuntos
Resistência à Insulina , Insulinas , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Glucose/metabolismo , Inflamação/metabolismo , Insulina/metabolismo , Insulinas/metabolismo , Insulinas/farmacologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ácido Mirístico , Obesidade/metabolismo , Resistina/metabolismo
13.
Sci Rep ; 12(1): 8936, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35624126

RESUMO

Adipokine human Resistin (hResistin), is known to be associated with insulin resistance and secrete low-grade pro-inflammatory cytokines in obesity. Although studies on low-grade inflammation of adipokine hResistin are known, studies on the effects and mechanisms of intervertebral disc degeneration (IVDD) are still lacking. Thus, we investigated the adipokine hResistin with or without pro-inflammatory cytokine IL-1ß in intervertebral disc (IVD) cells such as human annulus fibrosus (hAF) and nucleus pulposus (hNP). The protein expression changes in IL-1ß, IL-6, IL-8, MMP-1, MMP-3, and MMP-13, induced by the combined-hResistin and IL-1ß stimulation on hAF cells, was significantly greater than that of the same induced by mono-IL-1ß stimulation. Similarly, in the case of the protein expression change of inflammatory mediators induced by the combined-hResistin and IL-1ß stimulation on hNP cells was also significantly greater than that of the same induced by mono-IL-1ß stimulation. These results improve understanding of hResistin on inflammatory IVDD but also with other obesity-related inflammatory diseases.


Assuntos
Degeneração do Disco Intervertebral , Resistina , Adipocinas , Citocinas , Humanos , Degeneração do Disco Intervertebral/metabolismo , Obesidade/complicações , Resistina/metabolismo
14.
PLoS One ; 17(5): e0268291, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35536791

RESUMO

OBJECTIVE: We aimed to determine whether various novel inflammatory, angiogenic, and extracellular matrix-related mediators in amniotic fluid (AF) can independently predict emergency cerclage outcomes in women with acute cervical insufficiency (CI). METHODS: This was a retrospective cohort study conducted among 50 singleton pregnant women (18-25 weeks) who underwent emergency cerclage for CI and were subjected to amniocentesis. The AF samples were assayed for endoglin, endostatin, haptoglobin, insulin-like growth factor-binding protein (IGFBP)-3, -4, kallistatin, lumican, macrophage colony-stimulating factor (M-CSF), pentraxin 3, p-selectin, receptor for advanced glycation end products (RAGE), resistin, transforming growth factor beta-induced (TGFBI), and vitamin D-binding protein (VDBP) levels. Interleukin (IL)-6 levels in the AF were also measured for comparison with potential biomarkers assessed in this study. The primary endpoint was spontaneous preterm delivery (SPTD) at <34 weeks following emergency cerclage. RESULTS: The AF levels of pentraxin 3, RAGE, and resistin were significantly higher in women who had SPTD at <34 weeks after cerclage placement (pentraxin-3: P = 0.003; RAGE: P = 0.041; and resistin; P = 0.002). In multivariate analysis, elevated AF levels of pentraxin 3 (P = 0.007) and resistin (P = 0.006), but not those of RAGE (P = 0.069), were independently associated with the occurrence of SPTD at <34 weeks after cerclage, following adjustment for baseline clinical variables (e.g., cervical dilation). The area under the curve (AUC) values of AF pentraxin 3, RAGE, and resistin for the prediction of SPTD at <34 weeks were 0.749, 0.669, and 0.770, respectively, which were similar to those of AF IL-6. However, in univariate analyses, no differences in the AF levels of endoglin, endostatin, haptoglobin, IGFBP-3, IGFBP-4, kallistatin, lumican, p-selectin, TGFBI, and VDBP were found to be associated with SPTD at <34 weeks after cerclage placement. CONCLUSIONS: In women with acute CI, the AF levels of pentraxin 3, RAGE, and resistin could be useful novel biomarkers for predicting SPTD following emergency cerclage. However, the clinical utility of these new biomarkers should be validated in larger multicenter studies.


Assuntos
Cerclagem Cervical , Nascimento Prematuro , Incompetência do Colo do Útero , Líquido Amniótico/metabolismo , Biomarcadores/metabolismo , Endoglina/metabolismo , Endostatinas/metabolismo , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Feminino , Haptoglobinas/metabolismo , Humanos , Recém-Nascido , Interleucina-6/metabolismo , Lumicana/metabolismo , Selectina-P/metabolismo , Gravidez , Nascimento Prematuro/metabolismo , Resistina/metabolismo , Estudos Retrospectivos
15.
Inflammation ; 45(5): 1985-1999, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35411498

RESUMO

Cardiomyopathy is a well-known complication of sepsis that may deteriorate when accompanied by obesity. To test this hypothesis we fed C57black/6 male mice for 6 week with a high fat diet (60% energy) and submitted them to endotoxemic shock using E. coli LPS (10 mg/kg). Inflammatory markers (cytokines and adhesion molecules) were determined in plasma and heart tissue, as well as heart mitochondrial biogenesis and function. Obesity markedly shortened the survival rate of mouse after LPS injection and induced a persistent systemic inflammation since TNFα, IL-1ß, IL-6 and resistin plasma levels were higher 24 h after LPS injection. Heart tissue inflammation was significantly higher in obese mice, as detected by elevated mRNA expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα). Obese animals presented reduced maximum respiratory rate after LPS injection, however fatty acid oxidation increased in both groups. LPS decreased mitochondrial DNA content and mitochondria biogenesis factors, such as PGC1α and PGC1ß, in both groups, while NRF1 expression was significantly stimulated in obese mice hearts. Mitochondrial fusion/fission balance was only altered by obesity, with no influence of endotoxemia. Obesity accelerated endotoxemia death rate due to higher systemic inflammation and decreased heart mitochondrial respiratory capacity.


Assuntos
Endotoxemia , Animais , Citocinas/metabolismo , DNA Mitocondrial , Endotoxemia/metabolismo , Escherichia coli/metabolismo , Ácidos Graxos , Inflamação , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Obesos , Modelos Teóricos , Obesidade/complicações , Obesidade/metabolismo , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , RNA Mensageiro , Resistina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
PLoS One ; 17(3): e0265241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35286340

RESUMO

INTRODUCTION: Because of the strong correlation between the blood concentration of circulating resistin and the illness severity of septic patients, resistin has been proposed as a mediator of sepsis pathophysiology. In vitro data indicate that human resistin directly impairs neutrophil migration and intracellular bacterial killing, although the significance of these findings in vivo remain unclear. OBJECTIVE: The objectives of the present study were: (1) to validate the expression of human resistin in a clinically relevant, murine model of surgical sepsis, (2) to assess how sepsis-induced changes in resistin correlate with markers of infection and organ dysfunction, and (3) to investigate whether the expression of human resistin alters immune function or disease outcomes in vivo. METHODS: 107 male, C57BL/6 mice transgenic for the human resistin gene and its promoter elements (Retn+/-/-, or Retn+) were generated on a Retn-/- (mouse resistin knockout, or Rko) background. Outcomes were compared between age-matched transgenic and knockout mice. Acute sepsis was defined as the initial 24 h following cecal ligation and puncture (CLP). Physiologic and laboratory parameters correlating to the human Sequential Organ Failure Assessment (SOFA) Score were measured in mice, and innate immune cell number/function in the blood and peritoneal cavity were assessed. RESULTS: CLP significantly increased circulating levels of human resistin. The severity of sepsis-induced leukopenia was comparable between Retn+ and Rko mice. Resistin was associated with increased production of neutrophil reactive oxygen species, a decrease in circulating neutrophils at 6 h and an increase in peritoneal Ly6Chi monocytes at 6 h and 24 h post-sepsis. However, intraperitoneal bacterial growth, organ dysfunction and mouse survival did not differ with resistin production in septic mice. SIGNIFICANCE: Ex vivo resistin-induced impairment of neutrophil function do not appear to translate to increased sepsis severity or poorer outcomes in vivo following CLP.


Assuntos
Resistina , Sepse , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Insuficiência de Múltiplos Órgãos/metabolismo , Neutrófilos/metabolismo , Resistina/genética , Resistina/metabolismo
17.
Int J Mol Sci ; 23(3)2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35163020

RESUMO

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in the pathophysiological process associated with diabetes-related complications. The effect of high glucose levels on macrophage-derived exosomal MALAT1 is unknown. Therefore, we investigated the molecular regulatory mechanisms controlling exosomal MALAT1 in macrophages under high glucose treatment and the therapeutic target of macrophage-derived exosomal MALAT1 using a balloon injury model of vascular disease in diabetic rats. High glucose (25 mM) significantly increased MALAT1 expression in macrophage-derived exosomes. MALAT1 suppressed miR-150-5p expression in macrophage-derived exosomes under high-glucose conditions. Silencing MALAT1 using MALAT1 siRNA significantly reversed miR-150-5p expression induced by macrophage-derived exosomes. Macrophage-derived exosomes under high-glucose treatment significantly increased resistin expression in macrophages. Silencing MALAT1 and overexpression of miR-150-5p significantly decreased resistin expression induced by macrophage-derived exosomes. Overexpression of miR-150-5p significantly decreased resistin luciferase activity induced by macrophage-derived exosomes. Macrophage-derived exosome significantly decreased glucose uptake in macrophages and silencing MALAT1, resistin or overexpression of miR-150-5p significantly reversed glucose uptake. Balloon injury to the carotid artery significantly increased MALAT1 and resistin expression and significantly decreased miR-150-5p expression in arterial tissue. Silencing MALAT1 significantly reversed miR-150-5p expression in arterial tissue after balloon injury. Silencing MALAT1 or overexpression of miR-150-5p significantly reduced resistin expression after balloon injury. In conclusion, high glucose up-regulates MALAT1 to suppress miR-150-5p expression and counteracts the inhibitory effect of miR-150-5p on resistin expression in macrophages to promote vascular disease. Macrophage-derived exosomes containing MALAT1 may serve as a novel cell-free approach for the treatment of vascular disease in diabetes mellitus.


Assuntos
Doenças das Artérias Carótidas/patologia , Diabetes Mellitus Experimental/complicações , Glucose/toxicidade , Hiperglicemia/patologia , MicroRNAs/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , Resistina/metabolismo , Animais , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/metabolismo , Modelos Animais de Doenças , Exossomos/genética , Exossomos/metabolismo , Regulação da Expressão Gênica , Hiperglicemia/induzido quimicamente , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , RNA Longo não Codificante/genética , Ratos , Ratos Wistar , Resistina/genética , Edulcorantes/toxicidade
18.
Dig Dis Sci ; 67(7): 3006-3016, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34156590

RESUMO

BACKGROUND: Deregulation of immune response and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Resistin is a physiological modulator of inflammation and redox homeostasis of different cell types. Increased resistin serum concentration and the direct association between resistin hepatic expression and NAFLD severity suggest that resistin participates in NAFLD pathogenesis. AIMS: To evaluate resistin-induced regulation of redox homeostasis in mononuclear leukocytes from NAFLD patients and controls. METHODS: We evaluated basal and resistin-mediated modulation of reactive oxygen species (ROS) and glutathione content by flow cytometry, and antioxidant enzyme activities by spectrophotometry. RESULTS: Peripheral blood mononuclear cells (PBMC) from NAFLD patients showed higher ROS content and glutathione peroxidase activity and lower glutathione content, superoxide dismutase and glutathione reductase activities than control PBMC. Resistin decreased ROS levels and superoxide dismutase activity and increased glutathione reductase and catalase activities in PBMC from controls but not from patients. Resistin decreased glutathione content in PBMC from control and NAFLD patients, with greater effect on patient cells. Basal and resistin-modulated ROS levels were directly associated with obesity-related risk factors for NAFLD. Hepatic myeloid cells and T-lymphocytes from NAFLD patients showed higher basal ROS content than cells from controls. Resistin decreased ROS levels in hepatic T-lymphocytes from controls but not from patients. CONCLUSIONS: Resistin regulates redox homeostasis in mononuclear leukocytes. A decreased response to resistin in leukocytes from NAFLD patients is associated with an impaired redox homeostasis.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Antioxidantes/metabolismo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio , Resistina/metabolismo , Superóxido Dismutase/metabolismo
19.
Cardiovasc Res ; 118(8): 1947-1963, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34324657

RESUMO

AIMS: Increased resistin (Retn) levels are associated with development of cardiovascular diseases. However, the role of Retn in heart failure (HF) is still unclear. Here we probed the functional and molecular mechanism underlying the beneficial effect of Retn deletion in HF. METHODS AND RESULTS: Wild-type (WT) and adipose tissue-specific Retn-knockout (RKO) mice were subjected to transverse aortic constriction (TAC)-induced HF. Cardiac function and haemodynamic changes were measured by echocardiography and left ventricular catheterization. Adipose tissue Retn deletion attenuated while Retn cardiac-selective overexpression, via a recombinant adeno-associated virus-9 vector, exacerbated TAC-induced hypertrophy, cardiac dysfunction, and myocardial fibrosis in WT and RKO mice. Mechanistically, we showed that Gadd45α was significantly increased in RKO HF mice while cardiac overexpression of Retn led to its downregulation. miR148b-3p directly targets Gadd45α and inhibits its expression. Retn overexpression upregulated miR148b-3p expression and triggered DNA damage response (DDR) in RKO-HF mice. Inhibition of miR148b-3p in vivo normalized Gadd45α expression, decreased DDR, and reversed cardiac dysfunction and fibrosis. In vitro Retn overexpression in adult mouse cardiomyocytes activated miR148b-3p and reduced Gadd45α expression. Gadd45α overexpression in H9C2-cardiomyoblasts protected against hydrogen peroxide- and Retn-induced DDR. CONCLUSION: These findings reveal that diminution in circulating Retn reduced myocardial fibrosis and apoptosis, and improved heart function in a mouse model of HF, at least in part, through attenuation of miR148b-3p and DDR. The results of this study indicate that controlling Retn levels may provide a potential therapeutic approach for treating pressure overload-induced HF.


Assuntos
Dano ao DNA , Insuficiência Cardíaca , Resistina , Animais , Modelos Animais de Doenças , Fibrose , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Resistina/genética , Resistina/metabolismo , Remodelação Ventricular
20.
Dev Comp Immunol ; 128: 104327, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34863954

RESUMO

Haemophilus parasuis is a widespread bacterial pathogen causing acute systemic inflammation and leading to the sudden death of piglets. Resistin, a multifunctional peptide hormone previously demonstrated to influence the inflammation in porcine, was extremely increased in H. parasuis-infected tissues. However, the mechanism of resistin expression regulation in porcine, especially during pathogen infection, remains unclear. In the present study, we explored for the first time the transcription factor and signaling pathway mediating the expression of pig resistin during H. parasuis stimulation. We found that H. parasuis induced the expression of pig resistin in a time- and dose-dependent manner via the transcription factor Ets2 in porcine alveolar macrophages during H. parasuis stimulation. Moreover, the expression of Ets2 was mediated by the activation of the p38 MAPK pathway induced by H. parasuis, thus promoting resistin production. These results revealed a novel view of the molecular mechanism of pig resistin production during acute inflammation induced by pathogenic bacteria.


Assuntos
Infecções por Haemophilus , Haemophilus parasuis , Doenças dos Suínos , Animais , Infecções por Haemophilus/metabolismo , Haemophilus parasuis/fisiologia , Macrófagos Alveolares/metabolismo , Resistina/metabolismo , Suínos , Doenças dos Suínos/metabolismo , Doenças dos Suínos/microbiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...