scholarly journals Inflammation, obesity, and thrombosis

Blood ◽  
2013 ◽  
Vol 122 (20) ◽  
pp. 3415-3422 ◽  
Author(s):  
Fahumiya Samad ◽  
Wolfram Ruf
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Plasminogen Activator Inhibitor ◽  
Epidemiological Studies ◽  
Clinical Markers ◽  
Plasminogen Activator Inhibitor 1 ◽  
Protease Activated Receptors ◽  
The Metabolic Syndrome

Abstract Clinical and epidemiological studies support a connection between obesity and thrombosis, involving elevated expression of the prothrombotic molecules plasminogen activator inhibitor-1 and tissue factor (TF) and increased platelet activation. Cardiovascular diseases and metabolic syndrome–associated disorders, including obesity, insulin resistance, type 2 diabetes, and hepatic steatosis, involve inflammation elicited by infiltration and activation of immune cells, particularly macrophages, into adipose tissue. Although TF has been clearly linked to a procoagulant state in obesity, emerging genetic and pharmacologic evidence indicate that TF signaling via G protein-coupled protease-activated receptors (PAR2, PAR1) additionally drives multiple aspects of the metabolic syndrome. TF–PAR2 signaling in adipocytes contributes to diet-induced obesity by decreasing metabolism and energy expenditure, whereas TF–PAR2 signaling in hematopoietic and myeloid cells drives adipose tissue inflammation, hepatic steatosis, and insulin resistance. TF-initiated coagulation leading to thrombin–PAR1 signaling also contributes to diet-induced hepatic steatosis and inflammation in certain models. Thus, in obese patients, clinical markers of a prothrombotic state may indicate a risk for the development of complications of the metabolic syndrome. Furthermore, TF-induced signaling could provide new therapeutic targets for drug development at the intersection between obesity, inflammation, and thrombosis.

scholarly journals Tissue factor pathways linking obesity and inflammation

2015 ◽  
Vol 35 (03) ◽  
pp. 279-283 ◽  
Author(s):  
F. Samad ◽  
W. Ruf
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Tissue Factor ◽  
Clinical Markers ◽  
Protease Activated Receptors ◽  
Diet Induced Obesity ◽  
The Metabolic Syndrome ◽  
Amp Activated Protein Kinase ◽  
G Protein Coupled

SummaryObesity is a major cause for a spectrum of metabolic syndrome-related diseases that include insulin resistance, type 2 diabetes, and steatosis of the liver. Inflammation elicited by macrophages and other immune cells contributes to the metabolic abnormalities in obesity. In addition, coagulation activation following tissue factor (TF) upregulation in adipose tissue is frequently found in obese patients and particularly associated with diabetic complications. Genetic and pharmacological evidence indicates that TF makes significant contributions to the development of the metabolic syndrome by signaling through G protein-coupled protease activated receptors (PARs). Adipocyte TF-PAR2 signaling contributes to diet-induced obesity by decreasing metabolism and energy expenditure, whereas hematopoietic TF-PAR2 signaling is a major cause for adipose tissue inflammation, hepatic steatosis and inflammation, as well as insulin resistance. In the liver of mice on a high fat diet, PAR2 signaling increases transcripts of key regulators of gluconeogenesis, lipogenesis and inflammatory cytokines. Increased markers of hepatic gluconeogenesis correlate with decreased activation of AMP-activated protein kinase (AMPK), a known regulator of these pathways and a target for PAR2 signaling. Clinical markers of a TF-induced prothrombotic state may thus indicate a risk in obese patient for developing complications of the metabolic syndrome.

Inflammation, Obesity, and Thrombosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-45-SCI-45
Author(s):  
Fahumiya Samad ◽  
Leylla Badeanlou ◽  
Christian Furlan-Freguia ◽  
Guang Yang ◽  
Wolfram Ruf
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Weight Gain ◽  
Conflicts Of Interest ◽  
Plasminogen Activator Inhibitor ◽  
Cytoplasmic Domain ◽  
Epidemiological Studies ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Metabolic Syndrome ◽  
Adipose Inflammation

Abstract Abstract SCI-45 Clinical and epidemiological studies have long established a connection between obesity and thrombosis leading to increased cardiovascular complications, in part attributed to elevated expression of the prothrombotic molecules plasminogen activator inhibitor 1 and circulating tissue factor (TF). Obesity also increases the risk for metabolic dysfunction, and emerging evidence indicates that coagulation proteases offer a range of signaling pathways that control multiple aspects of the metabolic syndrome, including weight gain, insulin resistance, type 2 diabetes, and hepatic steatosis. While adipose inflammation due to recruitment and activation of macrophages and secretion of inflammatory cytokines promotes systemic hypercoagulability and insulin resistance, pathways that sustain adipose macrophage inflammation in obesity are unclear. Our studies suggest that TF signaling via the G-protein-coupled receptor, protease activated receptor 2 (PAR2), represents a novel link between obesity, coagulation, and associated adipose inflammation and insulin resistance. Mice lacking the cytoplasmic domain of TF or PAR2 were protected from high fat diet-induced weight gain, adipose inflammation, and insulin resistance. Genetic loss of TF cytoplasmic domain and PAR2 in myeloid cells attenuated adipose macrophage inflammation and increased insulin sensitivity, an effect that was also achieved by acute pharmacologic inhibition of TF-PAR2 signaling in macrophages. In contrast, TF signaling in nonhematopoietic cells specifically promoted obesity via its effects on energy metabolism. In adipocytes, TF-VIIa signaling suppressed basal and insulin-mediated AKT phosphorylation, with concordant transcriptional changes in genes regulating lipid and glucose metabolism. Thus, the procoagulant state induced by obesity can in fact contribute to the metabolic syndrome, and adipose TF signaling may be at the intersection between obesity, inflammation, and thrombosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Role of Plasminogen Activator Inhibitor-1 in the Metabolic Syndrome and Its Regulation

2014 ◽  
Vol 3 (6) ◽  
pp. 36 ◽  
Author(s):  
Martha Phelan ◽  
David M. Kerins
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Metabolic Syndrome ◽  
Activator Inhibitor ◽  
Pai 1

<p>Obesity is a major risk factor for cardiovascular disease (CVD). Lipid abnormalities, hypertension, impaired glucose tolerance or diabetes, are cardiovascular risk factors that are frequently present in patients with obesity. Haemostatic and fibrinolytic disturbances are also considered to be important risk factors for CVD hence, a potential link between CVD, obesity and the metabolic syndrome arises. Regulation of the fibrinolytic system can occur at the level of plasminogen activators and plasminogen activator inhibitor-1 (PAI-1). PAI-1, a glycoprotein, is one of the most important inhibitors of fibrinolysis. Regulation of this serine protease inhibitor may have a beneficial effect on other conditions associated with the metabolic syndrome. Human adipose tissue is a source of PAI-1. PAI-1 production may in turn be controlled by a number of hormones and cytokines which are secreted by adipose tissue in addition to dietary factors. In this review we summarise the current knowledge regarding the role of altered fibrinolytic function in obesity, CVD and hence the metabolic syndrome. Regulatory factors including different dietary components, weight loss and dietary intervention will also be discussed.</p>

scholarly journals Subcutaneous adipose tissue biology in metabolic syndrome

2018 ◽  
Vol 33 (1) ◽  
Author(s):  
Ishwarlal Jialal ◽  
Sridevi Devaraj
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Interleukin 1 ◽  
Plasminogen Activator Inhibitor ◽  
Retinol Binding Protein ◽  
Plasminogen Activator Inhibitor 1 ◽  
Amyloid A ◽  
Subcutaneous Adipose

AbstractMetabolic syndrome (MetS) is a common global problem that comprises the cardio-metabolic cluster and predisposes to both diabetes and cardiovascular diseases. Although the pathogenic mechanisms have not been elucidated, both increased inflammation and insulin resistance play a pivotal role. It appears that both monocyte/macrophages and adipose tissue (AT) conspire to accentuate both the pro-inflammatory state and increased insulin resistance. Whilst there are scant data on visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) biology, there are data on subcutaneous adipose tissue (SAT) dysregulation. There is a significant increase in macrophages and crown-like structures in the SAT of patients with MetS. With respect to adipokines, there is an increase in plasma leptin, plasminogen activator inhibitor-1, retinol-binding protein-4 (RBP-4), chemerin, serum amyloid-A, C-reactive protein (CRP), interleukin-1, -6, -8, lipopolysaccharide, fetuin A (FetA) and a decrease in adiponectin and omentin-1. All of the abnormalities in plasma were also confirmed for SAT-secreted adipokines except for adiponectin and RBP-4 which derive largely from VAT. As many of these biomediators correlate with both insulin resistance and increased inflammation, we can posit that dysregulation of SAT is detrimental and contributes to both the pathogenesis of MetS and its sequalae. Furthermore, as future directions, much work is needed with respect to VAT/EAT biology, autophagy, sirtuins, the gut microbiome, browning of AT, to further elucidate this common syndrome and identify potential therapeutic targets to forestall its serious complications.

scholarly journals The Relationship between Epicardial Adipose Tissue Thickness and Serum Interleukin-17a Level in Patients with Isolated Metabolic Syndrome

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 97 ◽  
Author(s):  
Esra Demir ◽  
Nazmiye Harmankaya ◽  
İrem Kıraç Utku ◽  
Gönül Açıksarı ◽  
Turgut Uygun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Epicardial Adipose Tissue ◽  
Control Group ◽  
Model Assessment ◽  
Tissue Thickness ◽  
The Metabolic Syndrome ◽  
Epicardial Adipose Tissue Thickness ◽  
The Relationship

In this study, it was aimed to investigate the relationship between the epicardial adipose tissue thickness (EATT) and serum IL-17A level insulin resistance in metabolic syndrome patients. This study enrolled a total of 160 subjects, of whom 80 were consecutive patients who applied to our outpatient clinic and were diagnosed with metabolic syndrome, and the other 80 were consecutive patients who were part of the control group with similar age and demographics in whom the metabolic syndrome was excluded. The metabolic syndrome diagnosis was made according to International Diabetes Federation (IDF)-2005 criteria. EATT was measured with transthoracic echocardiography (TTE) in the subjects. IL-17A serum levels were determined using the ELISA method. Fasting blood glucose, HDL, triglyceride, and fasting insulin levels were significantly higher in the metabolic syndrome group compared to the control group. In addition, the metabolic syndrome group had significantly higher high-sensitivity C-reactive protein (hs-CRP) and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) levels than the control group. Similarly, serum IL-17A levels were significantly elevated in the metabolic syndrome group compared to the control group statistically (p < 0.001). As well, EATT was higher in the metabolic syndrome than the control group. Conclusion: By virtue of their proinflammatory properties, EATT and IL-17 may play an important role in the pathogenesis of the metabolic syndrome.

scholarly journals Exercise Induced Adipokine Changes and the Metabolic Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Saeid Golbidi ◽  
Ismail Laher
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
The Body ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Before And After ◽  
Inflammatory State ◽  
Exercise Induced

The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

scholarly journals The Polycystic Ovary Syndrome and the Metabolic Syndrome: A Possible Chronobiotic-Cytoprotective Adjuvant Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Eduardo Spinedi ◽  
Daniel P. Cardinali
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
White Adipose Tissue ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
The Metabolic Syndrome ◽  
Obstructive Sleep ◽  
The Impact

Polycystic ovary syndrome is a highly frequent reproductive-endocrine disorder affecting up to 8–10% of women worldwide at reproductive age. Although its etiology is not fully understood, evidence suggests that insulin resistance, with or without compensatory hyperinsulinemia, and hyperandrogenism are very common features of the polycystic ovary syndrome phenotype. Dysfunctional white adipose tissue has been identified as a major contributing factor for insulin resistance in polycystic ovary syndrome. Environmental (e.g., chronodisruption) and genetic/epigenetic factors may also play relevant roles in syndrome development. Overweight and/or obesity are very common in women with polycystic ovary syndrome, thus suggesting that some polycystic ovary syndrome and metabolic syndrome female phenotypes share common characteristics. Sleep disturbances have been reported to double in women with PCOS and obstructive sleep apnea is a common feature in polycystic ovary syndrome patients. Maturation of the luteinizing hormone-releasing hormone secretion pattern in girls in puberty is closely related to changes in the sleep-wake cycle and could have relevance in the pathogenesis of polycystic ovary syndrome. This review article focuses on two main issues in the polycystic ovary syndrome-metabolic syndrome phenotype development: (a) the impact of androgen excess on white adipose tissue function and (b) the possible efficacy of adjuvant melatonin therapy to improve the chronobiologic profile in polycystic ovary syndrome-metabolic syndrome individuals. Genetic variants in melatonin receptor have been linked to increased risk of developing polycystic ovary syndrome, to impairments in insulin secretion, and to increased fasting glucose levels. Melatonin therapy may protect against several metabolic syndrome comorbidities in polycystic ovary syndrome and could be applied from the initial phases of patients’ treatment.

scholarly journals Plasma Plasminogen Activator Inhibitor-1 Levels and Nonalcoholic Fatty Liver in Individuals With Features of Metabolic Syndrome

2008 ◽  
Vol 14 (3) ◽  
pp. 319-324 ◽  
Author(s):  
Gabriela de Larrañaga ◽  
Silvia Perés Wingeyer ◽  
Mabel Graffigna ◽  
Susana Belli ◽  
Karla Bendezú ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Fatty Liver ◽  
Hdl Cholesterol ◽  
Insulin Level ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Fatty liver represents the liver component of metabolic syndrome and may be involved in plasminogen activator inhibitor-1 (PAI-1) synthesis. We studied plasma PAI-1 levels and relationships with risk factors for metabolic syndrome, including fatty liver, in 170 patients. Liver ultrasound scan was performed on all patients, and a liver biopsy was performed on those patients with chronically elevated transaminase levels. Plasma PAI-1 levels correlated significantly ( P < .05) with body mass index, degree of steatosis, insulin resistance, insulin level, waist circumference, triglycerides, and high-density lipoprotein (HDL) -cholesterol. However, only body mass index (β = .455) and HDL-cholesterol (β = .293) remained predictors of PAI-1 levels. Liver biopsy revealed a significant correlation ( P < .05) between insulin resistance ( r = 0.381) or insulin level ( r = 0.519) and liver fibrosis. In patients presenting features of metabolic syndrome, plasma PAI-1 levels were mainly conditioned by the whole-body fat content.

Sign in / Sign up

Export Citation Format

Share Document