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BACKGROUND AND AIMS: Ultra-microangiography (UMA) is a novel Doppler technique with optimized wall filtering that provides high sensitivity to low-velocity blood flows and optimized visualization of microcirculation. The aim of this pilot study was to compare intestinal vascularization assessed by color Doppler signals (CDS) and UMA. METHODS: We investigated intestinal vascularization using UMA and CDS in 13 patients with confirmed inflammatory bowel disease (IBD). A cohort of 28 patients without structural bowel disease served as the control. RESULTS: Microcirculation and dysregulated microcirculation in patients without and with inflammatory bowel disease can be visualized and quantified using UMA. In 83 % of IBD patients and 76% of non-IBD patients, a high resolution of intestinal perfusion could be achieved using UMA. CONCLUSIONS: To the best of our knowledge, this is the first study to investigate intestinal vascularization using UMA in patients with and without structural bowel disease. Quantification and visualization of intestinal vascularization should be further investigated in prospective studies and could help guide our therapy of patients with IBD.
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Intestinos , Microcirculação , Humanos , Projetos Piloto , Microcirculação/fisiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Intestinos/irrigação sanguínea , Intestinos/diagnóstico por imagem , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/fisiopatologia , Ultrassonografia Doppler em Cores , Angiografia/métodos , Idoso , Adulto Jovem , Valor Preditivo dos Testes , Estudos de Casos e ControlesRESUMO
BACKGROUND: Accurate biomarkers for disease activity and progression in patients with inflammatory bowel disease (IBD) are a prerequisite for individual disease characterization and personalized therapy. We show that metabolic profiling of serum from IBD patients is a promising approach to establish biomarkers. The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients in order to identify metabolic fingerprints unique to the disease. METHODS: Serum samples were obtained from 55 patients with Crohn's disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy control (HC) individuals and analyzed using proton nuclear magnetic resonance spectroscopy. Classification of patients and HC individuals was achieved by orthogonal partial least squares discriminant analysis and univariate analysis approaches. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale. RESULTS: Serum metabolome significantly differed between CD patients, UC patients, and HC individuals. The metabolomic differences of UC and CD patients compared with HC individuals were more pronounced than the differences between UC and CD patients. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein particles shifted from large to small dense particles in patients with CD. Of note, apolipoprotein A1 and A2 serum levels were decreased in CD and UC patients with higher fecal calprotectin levels. The Gastrointestinal Symptom Rating Scale is negatively associated with the concentration of apolipoprotein A2. CONCLUSIONS: Metabolomic assessment of serum samples facilitated the differentiation of IBD patients and HC individuals. These differences were constituted by changes in amino acid and lipoprotein levels. Furthermore, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.
The metabolic and lipidomic serum profile of patients with inflammatory bowel disease was analyzed using proton nuclear magnetic resonance spectroscopy. A significantly altered profile in comparison with healthy control individuals was identified, characterized by more atherogenic properties.
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Compensation of matrix effects is the main obstacle to achieve accurate quantification in LC-MS/MS. Therefore, quantitative LC-MS/MS typically relies on addition of internal standards (ISs). Here, we present a systematic comparison of ISs from a routine LC-MS/MS method for bile acid (BA) analysis with a focus on tauro-conjugated. Both human serum based quality control (QC) and patient samples were quantified with a variety of stable isotope labeled (SIL) BAs including D5-tauro BAs. As expected, SIL-ISs that match the endogenous analytes provide the highest data quality (precision, accuracy). We could not observe systematic correlation of data quality with chemical similarity or proximity in retention time of ISs to the analyte. However, both accuracy and precision of QCs and patient's concentrations showed significant correlation. This provides evidence that calculation of matrix-based QCs with various ISs could be applied for the selection of ISs whenever matching SILs are not available. Moreover, data calculated without ISs exhibited a poor data quality for both QCs and patients' concentrations. Considering these results, data generated without ISs should be interpreted with great care and may not be suitable for proposal of biomarkers unless solid quantitative data could confirm initial findings.
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Ácidos e Sais Biliares/sangue , Cromatografia Líquida/normas , Espectrometria de Massas em Tandem/normas , Humanos , Marcação por Isótopo , Controle de Qualidade , Padrões de ReferênciaRESUMO
OBJECTIVES: Several clinical studies have suggested the adipocytokine adiponectin is involved in the progression of rheumatoid arthritis (RA). From this point of view, adiponectin might present a new therapeutic target. However, as adiponectin also exerts beneficial effects in the human organism, a strategy that would allow its detrimental effects to be abolished while maintaining the positive effects would be highly favourable. To elucidate such a strategy, the authors analysed whether the different adiponectin isoforms induce diverging effects, especially with regard to rheumatoid arthritis synovial fibroblasts (RASF), a central cell type in RA pathogenesis capable of invading into and destroying cartilage. METHODS: Affymetrix microarrays were used to screen for changes in gene expression of RASF. Messenger RNA levels were quantified by real-time PCR, protein levels by immunoassay. The migration of RASF and primary human lymphocytes was analysed using a two-chamber migration assay. RESULTS: In RASF, the individual adiponectin isoforms induced numerous genes/proteins relevant in RA pathogenesis to clearly different extents. In general, the most potent isoforms were the high molecular weight/middle molecular weight isoforms and the globular isoform, while the least potent isoform was the adiponectin trimer. The chemokines secreted by RASF upon adiponectin stimulation resulted in an increased migration of RASF and lymphocytes. CONCLUSION: The results clearly suggest a pro-inflammatory and joint-destructive role of all adiponectin isoforms in RA pathophysiology, indicating that in chronic inflammatory joint diseases the detrimental effects outweigh the beneficial effects of adiponectin.
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Adiponectina/metabolismo , Artrite Reumatoide/metabolismo , Fibroblastos/metabolismo , Adiponectina/imunologia , Artrite Reumatoide/imunologia , Células Cultivadas , Quimiocinas/biossíntese , Fibroblastos/imunologia , Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membrana Sinovial/metabolismoRESUMO
BACKGROUND: The adipokine CTRP-3 (C1q/TNF-related protein-3) belongs to the C1q/TNF-related protein family which antagonizes the effects of lipopolysaccharide (LPS). The aim was to investigate the antiinflammatory and antifibrotic role of CTRP-3 in Crohn's disease (CD). METHODS: Mesenteric adipose tissue (MAT) of patients with CD or colonic cancer (CC) was resected. Human primary colonic lamina propria fibroblasts (CLPF) were isolated from controls and CD patients. Concentrations of chemokines and cytokines in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Expression of connective tissue growth factor (CTGF), collagen I, and collagen III was analyzed by real-time polymerase chain reaction (PCR). Recombinant CTRP-3 expressed in insect cells was used for stimulation experiments. RESULTS: CTRP-3 is synthesized and secreted by MAT resected from patients with CD, ulcerative colitis (UC), CC, and sigma diverticulitis as well as by murine and human mature adipocytes. CTRP-3 had no effect on the basal secretion of MCSF, MIF, or RANTES in MAT of CD and control patients. LPS-stimulation (10 ng/mL) significantly increased IL-8 release in CLPF of CD patients and, to a lesser extent, in cells of controls and of fibrotic CD tissue. CTRP-3 significantly and dose-dependently reduced LPS-induced IL-8 secretion in CLPF within 8 hours after LPS exposure, whereas LPS-induced IL-6 and TNF release was not affected. CTRP-3 inhibited TGF-ß production and the expression of CTGF and collagen I in CLPF, whereas collagen III expression remained unchanged. CONCLUSIONS: CTRP-3 exerts potent antiinflammatory and antifibrotic effects in CLPF by antagonizing the LPS pathway and by targeting the TGF-ß-CTGF-collagen I pathway.
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Anti-Inflamatórios/farmacologia , Colo/metabolismo , Neoplasias do Colo/prevenção & controle , Doença de Crohn/prevenção & controle , Fibroblastos/metabolismo , Fibrose/prevenção & controle , Gordura Intra-Abdominal/metabolismo , Fatores de Necrose Tumoral/farmacologia , Adipocinas/genética , Adipocinas/metabolismo , Adulto , Idoso , Western Blotting , Células Cultivadas , Quimiocinas/genética , Quimiocinas/metabolismo , Colo/imunologia , Colo/patologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Doença de Crohn/imunologia , Doença de Crohn/patologia , Citocinas/genética , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/imunologia , Fibroblastos/patologia , Fibrose/imunologia , Fibrose/patologia , Humanos , Lipopolissacarídeos/farmacologia , Masculino , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVES: Peripancreatic necrosis determines clinical severity in acute pancreatitis. Early markers predicting peripancreatic necrosis and clinical severity are lacking. Because adipocytes of peripancreatic adipose tissue secret highly active adipocytokines, the aim of the study was to investigate whether adipocytokines are able to serve as early markers predicting peripancreatic necrosis and clinical severity. METHODS: A total of 50 patients (20 women, 30 men) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and the APACHE (Acute Physiology And Chronic Health Evaluation) II score. Pancreatic and peripancreatic necrosis were quantified by using the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Adiponectin, leptin, and resistin were measured at admission and daily for at least 10 days by enzyme-linked immunosorbent assay. RESULTS: In contrast to admission C-reactive protein values, admission resistin values were significantly correlated with clinical severity and even with clinical end points such as death and need for interventions. Admission resistin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver-operator characteristics that admission resistin concentration provides a positive predictive value of 89% in predicting the extent of peripancreatic necrosis (area under the curve, 0.8; P=0.002; sensitivity, 80%; specificity, 70%) by using a cutoff value of 11.9 ng/ml. CONCLUSIONS: Admission resistin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Resistin may have potential for clinical use as a new and diagnostic serum marker.
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Pâncreas/patologia , Pancreatite Necrosante Aguda/sangue , Resistina/sangue , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pancreatite Necrosante Aguda/diagnóstico por imagem , Pancreatite Necrosante Aguda/patologia , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Radiografia , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased production of adipokines, which are cytokine-like mediators that are produced mainly in adipose tissue but also in synovial cells. Since RA synovial fibroblasts (RASFs), lymphocytes, endothelial cells, and chondrocytes are key players in the pathophysiology of RA, this study was undertaken to analyze the effects of the key adipokine adiponectin on proinflammatory and prodestructive synovial effector cells. METHODS: Lymphocytes were activated in part prior to stimulation. All cells were stimulated with adiponectin, and changes in gene and protein expression were determined by Affymetrix and protein arrays. Messenger RNA and protein levels were confirmed using semiquantitative reverse transcription-polymerase chain reaction (PCR), real-time PCR, and immunoassays. Intracellular signal transduction was evaluated using chemical signaling inhibitors. RESULTS: Adiponectin stimulation of human RASFs predominantly induced the secretion of chemokines, as well as proinflammatory cytokines, prostaglandin synthases, growth factors, and factors of bone metabolism and matrix remodeling. Lymphocytes, endothelial cells, and chondrocytes responded to adiponectin stimulation with enhanced synthesis of cytokines and various chemokines. Additionally, chondrocytes released increased amounts of matrix metalloproteinases. In RASFs, adiponectin-mediated effects were p38 MAPK and protein kinase C dependent. CONCLUSION: Our previous findings indicated that adiponectin was present in inflamed synovium, at sites of cartilage invasion, in lymphocyte infiltrates, and in perivascular areas. The findings of the present study indicate that adiponectin induces gene expression and protein synthesis in human RASFs, lymphocytes, endothelial cells, and chondrocytes, supporting the concept of adiponectin being involved in the pathophysiologic modulation of RA effector cells. Adiponectin promotes inflammation through cytokine synthesis, attraction of inflammatory cells to the synovium, and recruitment of prodestructive cells via chemokines, thus promoting matrix destruction at sites of cartilage invasion.
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Adiponectina/fisiologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Quimiocinas/metabolismo , Fibroblastos/metabolismo , Membrana Sinovial/fisiopatologia , Estudos de Casos e Controles , Células Cultivadas , Condrócitos/metabolismo , Células Endoteliais/metabolismo , Perfilação da Expressão Gênica , Humanos , Inflamação/fisiopatologia , Articulação do Joelho/fisiopatologia , Linfócitos/metabolismo , Osteoartrite do Joelho , Análise Serial de ProteínasRESUMO
No detailed data are available on hepatic clearance, postprandial release, and distribution profile of metabolically active adipokines in splanchnic blood compartments such as portal and hepatic veins. This would be a prerequisite for understanding the role of visceral adipose tissue-derived adipokines in metabolism. Adiponectin, resistin, leptin, and visfatin concentrations were measured by enzyme-linked immunosorbent assay in peripheral veins, arterial blood, hepatic veins, and portal veins in 50 patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic shunt implantation, in 6 patients with normal liver function, and in fasted and fed rats. Adiponectin, leptin, resistin, and visfatin did not differ among blood compartments in normal-weight probands in the fasted state. Adiponectin and leptin levels were similar in patients with and without liver cirrhosis. Systemic visfatin levels were decreased and resistin levels were increased in liver cirrhosis. Visfatin secretion was higher from visceral than from peripheral subcutaneous adipose tissue in liver cirrhosis. There was no hepatic clearance of visfatin. Leptin secretion was higher from peripheral than from visceral adipose tissue. Leptin did not undergo hepatic clearance. Resistin and adiponectin did not differ between blood compartments in liver cirrhosis. Resistin concentrations increased upon feeding in rats, and there was an increase in the postprandial clearance of adiponectin by the liver. A postprandial increase of leptin concentrations was restricted to peripheral adipose tissue in rats. The results give insight into the dynamics of splanchnic adipokine concentrations and help critically interpret data derived from messenger RNA expression studies.
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Adipocinas/sangue , Gordura Intra-Abdominal/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , Adiponectina/sangue , Animais , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Veias Hepáticas/metabolismo , Humanos , Leptina/sangue , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue , Veia Porta/metabolismo , Período Pós-Prandial , Ratos , Ratos Sprague-Dawley , Resistina/sangue , Circulação Esplâncnica , Estatísticas não ParamétricasRESUMO
AIMS/HYPOTHESIS: It was the aim to investigate the hypothesis that the new C1q/TNF-family member CTRP-3 (C1q/TNF-related protein-3) acts anti-inflammatory in human monocytes from healthy controls and patients with type 2 diabetes mellitus (T2D). METHODS: Monocytes were isolated from 20 healthy controls and 30 patients with T2D. IL-6 and TNF concentrations were measured by ELISA. CTRP-3 was expressed in insect cells and used for stimulation experiments. RESULTS: Basal IL-6 and TNF were not different in control and in T2D monocytes. LPS-stimulation (1 microg/ml) significantly (p<0.001) increased IL-6 and TNF in the supernatants of control and in T2D monocytes to a similar extent. CTRP-3 (1 microg/ml) significantly (p=0.03) inhibited LPS-induced IL-6 in control monocytes but not in T2D monocytes. TNF upon co-stimulation with LPS and CTRP-3 was significantly (p=0.012) lower in control than in T2D monocytes. LPS-induced TNF concentration was significantly and positively correlated with serum total cholesterol and LDL cholesterol in T2D patients. CONCLUSIONS: CTRP-3 inhibits LPS-induced IL-6 and TNF release. This anti-inflammatory effect is lost in T2D. Serum cholesterol concentration affects the pro-inflammatory potential of LPS to induce TNF release from T2D monocytes in the presence or absence of CTRP-3. CTRP-3 might partly account for the pro-inflammatory state in T2D.
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Adiponectina/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/imunologia , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Fatores de Necrose Tumoral/metabolismo , Adulto , Idoso , Animais , Células Cultivadas , Feminino , Humanos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Fator de Necrose Tumoral alfa/metabolismo , Fatores de Necrose Tumoral/genética , Adulto JovemRESUMO
Compared with bone marrow-derived mesenchymal stem cells, adipose tissue-derived stromal cells (ADSC) do have an equal potential to differentiate into cells and tissues of mesodermal origin, such as adipocytes, cartilage, bone, and skeletal muscle. However, the easy and repeatable access to subcutaneous adipose tissue and the simple isolation procedures provide a clear advantage. Since extensive reviews focusing exclusively on ADSC are rare, it is the aim of this review to describe the preparation and isolation procedures for ADSC, to summarize the molecular characterization of ADSC, to describe the differentiation capacity of ADSC, and to discuss the mechanisms and future role of ADSC in cell therapy and tissue engineering. An initial effort has also been made to differentiate ADSC into hepatocytes, endocrine pancreatic cells, neurons, cardiomyocytes, hepatocytes, and endothelial/vascular cells. Whereas the lineage-specific differentiation into cells of mesodermal origin is well understood on a molecular basis, the molecular key events and transcription factors that initially allocate the ADSC to a lineage-specific differentiation are almost completely unknown. Decoding these molecular mechanisms is a prerequisite for developing novel cell therapies.
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Tecido Adiposo/citologia , Células Estromais/citologia , Células Estromais/transplante , Diferenciação Celular , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Mesoderma/citologia , Engenharia TecidualRESUMO
BACKGROUND AND AIM: Severe acute pancreatitis is characterized by lipase-induced peripancreatic fat cell necrosis. Because adipocytes secret several highly active molecules, the aim of the present study was to investigate the hypothesis that adipocytokines could serve as potential markers predicting peripancreatic necrosis and severity in acute pancreatitis. METHODS: A total of 23 patients (11 females, 12 males) with acute pancreatitis were included and a computed tomography (CT) examination was available in 20 patients. Balthazar score, Schröder score, pancreatic necrosis score, Ranson score and APACHE II score were calculated, correlated with biochemical parameters and analyzed using receiver-operator characteristics (ROC) analysis. Adipocytokine serum levels were measured daily by enzyme-linked immunosorbent assay (ELISA) over 10 days after admission. RESULTS: Resistin and leptin were significantly elevated in patients with severe pancreatitis and were correlated with a radiological scoring system for extrapancreatic necrosis. Whereas resistin correlated positively with clinical scoring systems, time until discharge and the need for interventions, leptin was correlated positively with C-reactive protein (CRP) levels. Resistin levels measured on the day of admittance had a positive predictive value of 93.3% (cut-off: >6.95 ng/mL) in predicting a Schröder score >3. CONCLUSION: Resistin, and to a lesser extent leptin, but not adiponectin levels are novel potential markers for extrapancreatic necrosis and severity of acute pancreatitis and should therefore be tested in larger cohorts of patients.
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Adiponectina/sangue , Leptina/sangue , Pâncreas/patologia , Pancreatite/sangue , Pancreatite/patologia , Resistina/sangue , APACHE , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Projetos Piloto , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Creeping fat represents a characteristic feature of Crohn's disease (CD) and adipose tissue is currently being recognized as a complex compartment secreting highly active molecules. Pro- or anti-inflammatory adipose tissue-derived secretory products (adipocytokines) might play a role in the pathogenesis of CD. METHODS: Adipose tissue specimens were obtained from creeping fat contiguous to the involved intestine of 10 patients with CD. Mesenteric adipose tissue specimens resected in 13 patients with colon cancer (CC) and in seven patients with diverticulitis (DIV) served as controls. Three fat tissue specimens per well and n = 6-8 wells per patient were incubated ex vivo for 24 h. The release of regulated on activation, T-cell expressed and secreted (RANTES) and interleukin (IL)-10 into the supernatant was measured by ELISA. RESULTS: Both RANTES and IL-10 secretion could be demonstrated from total adipose tissue explants. The RANTES secretion is increased from creeping fat in CD (3691 +/- 597 pg/g fat per 24 h) when compared to mesenteric adipose tissue from patients with CC (1690 +/- 191 pg/g fat per 24 h; P < 0.0001) or DIV (1672 +/- 336 pg/g fat per 24 h; P < 0.0001). In contrast, IL-10 secretion is downregulated significantly only in patients with DIV (1418 +/- 180 pg/g fat per 24 h; P = 0.016) when compared to CC patients (2368 +/- 259 pg/g fat per 24 h). Crohn's disease patients receiving steroids had a higher secretion rate of RANTES and IL-10. CONCLUSIONS: Both RANTES and IL-10 secretion can be detected from mesenteric adipose tissue and from creeping fat. The elevated RANTES and IL-10 secretion from creeping fat in CD is not due to a CD-specific effect but caused by steroid treatment.
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Tecido Adiposo/metabolismo , Quimiocina CCL5/metabolismo , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Interleucina-10/metabolismo , Esteroides/uso terapêutico , Adulto , Proteína C-Reativa/metabolismo , Quimiocinas/metabolismo , Neoplasias do Colo/metabolismo , Doença de Crohn/patologia , Doença de Crohn/fisiopatologia , Citocinas/metabolismo , Diverticulite/metabolismo , Feminino , Humanos , Masculino , Mesentério/metabolismo , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Creeping fat represents a characteristic feature of Crohn's disease (CD), and adipose tissue secretes adipocytokines and chemokines/growth factors such as vascular endothelial growth factor (VEGF). Because VEGF serum levels and mucosal VEGF expression is elevated in CD patients, the aim of the present paper was to investigate creeping fat-derived VEGF secretion in CD. MATERIAL AND METHODS: Adipose tissue was obtained from creeping fat of 10 patients with CD. Mesenteric adipose tissue was resected from 13 patients with colon cancer (CC) and from seven patients with diverticulitis (DIV). Three fat tissue specimens per well, and several wells (6-8) per patient were incubated ex vivo for 24 h. The release of VEGF into the supernatant was measured by ELISA. RESULTS: There was stable VEGF secretion from mesenteric adipose tissue of patients with CC or DIV and from creeping fat of patients with CD. Whereas the VEGF secretion rate was not different between patients with CD (465 +/- 98 pg/g fat per 24 h) and CC (399 +/- 48 pg/g fat per 24 h), VEGF secretion was significantly reduced in patients suffering from DIV (115 +/- 41 pg/g fat per 24 h; P < 0.0001 and P = 0.001, respectively). The CD patients treated with steroids had significantly lower VEGF secretion rates (294 +/- 42 pg/g fat per 24 h) than CD patients not receiving steroids (607 +/- 105 pg/g fat per 24 h; P = 0.001). CONCLUSIONS: Creeping fat is an important source of VEGF secretion. The characteristics of the inflammatory changes in CD might be due to the lack of VEGF downregulation that is seen in DIV.
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Tecido Adiposo/metabolismo , Doença de Crohn/metabolismo , Mesentério , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Animais , Neoplasias do Colo/metabolismo , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Diverticulite/metabolismo , Feminino , Humanos , Masculino , Mesentério/anatomia & histologia , Mesentério/metabolismo , Pessoa de Meia-Idade , Esteroides/uso terapêuticoRESUMO
Adipose tissue has long been regarded as a passive type of connective tissue that stores energy as triglycerides and releases energy as free fatty acids, however, this point of view has now changed. The wide variety of products expressed and secreted by adipose tissue, such as adiponectin, leptin, and resistin, mean that the total adipose tissue mass can be defined as a real endocrine organ. The anatomic, metabolic and biochemical characteristics of visceral adipose tissue make it interesting in the context of intestinal and mesenteric diseases. These characteristics include increased lipolysis, venous drainage via the portal vein and local glucocorticoid excess owing to the specific expression of 11-beta-hydroxysteroid-dehydrogenase type 1. In this review, the role of the visceral adipose tissue and its secretory products in intestinal and mesenteric diseases is systematically reviewed, with special focus on 'creeping fat' in Crohn's disease and mesenteric panniculitis.
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Adipócitos/imunologia , Tecido Adiposo/imunologia , Citocinas/imunologia , Enteropatias/imunologia , Doenças Peritoneais/imunologia , Tecido Adiposo/efeitos dos fármacos , Doença de Crohn/imunologia , Humanos , Mesentério , Obesidade/imunologia , Paniculite Peritoneal/imunologia , VíscerasRESUMO
There is increasing evidence that visceral adipose tissue is a causative risk factor for fatty liver and nonalcoholic steatohepatitis. Adipose tissue-derived secretory proteins are collectively named adipocytokines. Obesity and mainly visceral fat accumulation impair adipocyte function and adipocytokine secretion and the altered release of these proteins contributes to hypertension, impaired fibrinolysis and insulin resistance. This review summarizes recent findings on the role of the adipocytokines adiponectin, leptin and resistin in the context of hepatic insulin resistance, fatty liver and liver fibrosis. Elevated levels of resistin antagonize hepatic insulin action and raise plasma glucose levels. Leptin exerts insulin-sensitizing effects, but obesity has been linked to leptin resistance and low levels of circulating leptin receptor, indicating that high levels of leptin cannot mediate its beneficial effects. Adiponectin improves insulin sensitivity; however, low circulating adiponectin is found in the obese state. Adiponectin is an anti-inflammatory protein, whereas leptin augments inflammation and fibrogenesis. Disturbed adipocytokine secretion might, therefore, promote hepatic steatosis and the development of nonalcoholic steatohepatitis. The beneficial effects of the therapeutic approaches so far tested in the treatment of fatty liver disease and fibrosis might be due to the modulation of these adipocytokines.
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Adipócitos/metabolismo , Tecido Adiposo/imunologia , Citocinas/imunologia , Fígado Gorduroso/imunologia , Adipócitos/imunologia , Tecido Adiposo/metabolismo , Fígado Gorduroso/fisiopatologia , Glucose/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina/imunologia , Leptina/imunologia , Cirrose Hepática/imunologia , Cirrose Hepática/fisiopatologia , Obesidade/imunologia , Vísceras/imunologiaRESUMO
After transformation of the Streptomyces lividans chloramphenicol-sensitive, arginine-auxotrophic mutant strain AJ100 with a derivative of plasmid SCP2, some of the regenerated protoplasts contained an 8.2 kb DNA sequence amplified to several hundred copies per chromosome. The corresponding non-amplified sequence, called AUD4, was isolated from a lambda phage genomic library of S. lividans 1326. Two cytosine residues were the only directly repeated nucleotides at the ends of the element, indicating that AUD4 is a class I amplifiable sequence. The element mapped in the AseI-D fragment of the S. lividans chromosome, where other class I amplifications have been described. The complete element was sequenced and 10 ORFs were identified. Some of the deduced proteins are highly conserved in other organisms but a putative function could be attributed to only a few of them. Duplication of AUD4 by integration of an Escherichia coli plasmid carrying various parts of AUD4 and a thiostrepton-resistance gene in S. lividans AJ100, ZX7 or TK64 induced amplification of the integrated plasmid, AUD4 or both at high frequency.