Alterations of the classic pathway of complement in adipose tissue of obesity and insulin resistance

2007 ◽  
Vol 292 (5) ◽  
pp. E1433-E1440 ◽  
Author(s):  
Jinhui Zhang ◽  
Wendy Wright ◽  
David A. Bernlohr ◽  
Samuel W. Cushman ◽  
Xiaoli Chen
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Epididymal Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Insulin Resistant ◽  
Obese Rats ◽  
Initial Activation ◽  
Adipose Cells ◽  
Classic Pathway

Adipose tissue inflammation has recently been linked to the pathogenesis of obesity and insulin resistance. C1 complex comprising three distinct proteins, C1q, C1r, and C1s, involves the key initial activation of the classic pathway of complement and plays an important role in the initiation of inflammatory process. In this study, we investigated adipose expression and regulation of C1 complement subcomponents and C1 activation regulator decorin in obesity and insulin resistance. Expression of C1q in epididymal adipose tissue was increased consistently in ob/ob mice, Zucker obese rats, and high fat-diet-induced obese (HF-DIO) mice. Decorin was found to increase in expression in Zucker obese rats and HF-DIO mice but decrease in ob/ob mice. After TZD administration, C1q and decorin expression was reversed in Zucker obese rats and HF-DIO mice. Increased expression of C1 complement and decorin was observed in both primary adipose and stromal vascular cells isolated from Zucker obese rats. Upregulation of C1r and C1s expression was also perceived in adipose cells from insulin-resistant humans. Furthermore, expression of C1 complement and decorin is dysregulated in TNF-α-induced insulin resistance in 3T3-L1 adipocytes and cultured rat adipose cells as they become insulin resistant after 24-h culture. These data suggests that both adipose and immune cells are the sources for abnormal adipose tissue production of C1 complement and decorin in obesity. Our findings also demonstrate that excessive activation of the classic pathway of complement commonly occurs in obesity, suggesting its possible role in adipose tissue inflammation and insulin resistance.

scholarly journals Obesity/insulin resistance rather than liver fat increases coagulation factor activities and expression in humans

2017 ◽  
Vol 117 (02) ◽  
pp. 286-294 ◽  
Author(s):  
Susanna Lallukka ◽  
Panu K. Luukkonen ◽  
You Zhou ◽  
Elina Isokuortti ◽  
Marja Leivonen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Liver Fat ◽  
Adipose Tissue Inflammation ◽  
Inflammatory Genes ◽  
Tissue Inflammation ◽  
Hepatic Expression ◽  
Insulin Resistant

SummaryIncreased liver fat may be caused by insulin resistance and adipose tissue inflammation or by the common I148M variant in PNPLA3 at rs738409, which lacks both of these features. We hypothesised that obesity/insulin resistance rather than liver fat increases circulating coagulation factor activities. We measured plasma prothrombin time (PT, Owren method), activated partial thromboplastin time (APTT), activities of several coagulation factors, VWF:RCo and fibrinogen, and D-dimer concentration in 92 subjects divided into groups based on insulin sensitivity [insulin-resistant (‘IR’) versus insulin-sensitive (‘IS’)] and PNPLA3 genotype (PNPLA3148MM/MI vs PNPLA3148II). Liver fat content (1H-MRS) was similarly increased in ‘IR’ (13 ± 1 %) and PNPLA3148MM/MI (12 ± 2 %) as compared to ‘IS’ (6 ± 1 %, p < 0.05) and PNPLA3148II (8 ± 1 %, p < 0.05), respectively. FVIII, FIX, FXIII, fibrinogen and VWF:RCo activities were increased, and PT and APTT shortened in ‘IR’ versus ‘IS’, in contrast to these factors being similar between PNPLA3148MM/MI and PNPLA3148II groups. In subjects undergoing a liver biopsy and entirely lacking the I148M variant, insulin-resistant subjects had higher hepatic expression of F8, F9 and FGG than equally obese insulin-sensitive subjects. Expression of pro-inflammatory genes in adipose tissue correlated positively with PT (% of normal), circulating FVIII, FIX, FXI, VWR:RCo and fibrinogen, and expression of anti-inflammatory genes negatively with PT (%), FIX and fibrinogen. We conclude that obesity/insulin resistance rather than an increase in liver fat is associated with a procoagulant plasma profile. This reflects adipose tissue inflammation and increased hepatic production of coagulation factors and their susceptibility for activation.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Adipokines as Drug Targets in Diabetes and Underlying Disturbances

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Vinícius Andrade-Oliveira ◽  
Niels O.S. Câmara ◽  
Pedro M. Moraes-Vieira
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Drug Targets ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Low Grade ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Therapeutic Implications ◽  
Insulin Resistant

Diabetes and obesity are worldwide health problems. White fat dynamically participates in hormonal and inflammatory regulation. White adipose tissue is recognized as a multifactorial organ that secretes several adipose-derived factors that have been collectively termed “adipokines.” Adipokines are pleiotropic molecules that gather factors such as leptin, adiponectin, visfatin, apelin, vaspin, hepcidin, RBP4, and inflammatory cytokines, including TNF and IL-1β, among others. Multiple roles in metabolic and inflammatory responses have been assigned to these molecules. Several adipokines contribute to the self-styled “low-grade inflammatory state” of obese and insulin-resistant subjects, inducing the accumulation of metabolic anomalies within these individuals, including autoimmune and inflammatory diseases. Thus, adipokines are an interesting drug target to treat autoimmune diseases, obesity, insulin resistance, and adipose tissue inflammation. The aim of this review is to present an overview of the roles of adipokines in different immune and nonimmune cells, which will contribute to diabetes as well as to adipose tissue inflammation and insulin resistance development. We describe how adipokines regulate inflammation in these diseases and their therapeutic implications. We also survey current attempts to exploit adipokines for clinical applications, which hold potential as novel approaches to drug development in several immune-mediated diseases.

scholarly journals IL-1 family members in the pathogenesis and treatment of metabolic disease: Focus on adipose tissue inflammation and insulin resistance

Cytokine ◽  
2015 ◽  
Vol 75 (2) ◽  
pp. 280-290 ◽  
Author(s):  
Dov B. Ballak ◽  
Rinke Stienstra ◽  
Cees J. Tack ◽  
Charles A. Dinarello ◽  
Janna A. van Diepen
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Family Members ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Disease Focus

scholarly journals Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Charmaine S. Tam ◽  
Leanne M. Redman
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Proinflammatory Mediators ◽  
Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

scholarly journals Glucose-6-Phosphate Dehydrogenase Deficiency Improves Insulin Resistance With Reduced Adipose Tissue Inflammation in Obesity

Diabetes ◽  
2016 ◽  
Vol 65 (9) ◽  
pp. 2624-2638 ◽  
Author(s):  
Mira Ham ◽  
Sung Sik Choe ◽  
Kyung Cheul Shin ◽  
Goun Choi ◽  
Ji-Won Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Dehydrogenase Deficiency ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Glucose 6 Phosphate Dehydrogenase

scholarly journals Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Kyung Cheul Shin ◽  
Injae Hwang ◽  
Sung Sik Choe ◽  
Jeu Park ◽  
Yul Ji ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation

scholarly journals The role of uncoupling protein 2 in macrophages and its impact on obesity-induced adipose tissue inflammation and insulin resistance

2020 ◽  
Vol 295 (51) ◽  
pp. 17535-17548
Author(s):  
Xanthe A. M. H. van Dierendonck ◽  
Tiphaine Sancerni ◽  
Marie-Clotilde Alves-Guerra ◽  
Rinke Stienstra
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Macrophage Activation ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Obesity And Diabetes ◽  
Adipose Tissue Macrophages

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.

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