Inflammation may modulate IL6 and C-reactive protein gene expression in the adipose tissue: the role of IL6 cell membrane receptor (original) (raw)
Related papers
2007
Only few studies have been addressed to the presence and regulation of C-reactive protein (CRP) gene expression in different districts of adipose tissue, and no study has investigated the role of adipose tissue in presence of inflammation. Therefore, the aim of this study was to investigate the inflammatory involvement of either adipose tissue or adipose cells (adipocytes and stromal cells, respectively) in patients with chronic inflammatory disease, focusing on regional adipose tissue CRP gene expression. Eighteen patients with inflammatory disease and 14 healthy controls were enrolled. All subjects underwent specific surgical procedures. Inflamed and noninflamed patients provided samples of subcutaneous and/or omental adipose tissue. All samples were analyzed by RT-PCR and real-time PCR for specific gene expression. In addition, both adipocytes and stromal cells were studied by real-time PCR and immunoprecipitation to evaluate either gene or protein expression of CRP. Our results (real-time PCR) demonstrated a higher gene expression of CRP, IL-6, and both IL-6 membrane receptors in subcutaneous samples of inflamed patients than in healthy controls. Furthermore, in omental fragments of inflamed patients, an enhanced mRNA abundance of the same genes, compared with subcutaneous, was observed. The results obtained at cellular level did not provide evidence of any difference between adipocytes and stromal cell CRP gene expression, whereas immunoprecipitation demonstrated the presence of CRP in inflamed subjects. These results provide first-time evidence of the involvement of adipose tissue in the course of chronic inflammatory diseases, with a different degree of participation of the different adipose tissue districts. interleukin-6; interleukin-6 receptors CENTRAL ADIPOSE TISSUE is currently recognized (5, 20) as a rich milieu and source of interleukin-6 (IL-6). Circulating levels of IL-6 may be increased in obese individuals and linked with coronary artery disease (15, 16, 27). Studies measuring arterovenous increase of serum IL-6 (11) have clearly shown a net secretion of IL-6 by adipose tissue depots, suggesting that fat accounts for roughly 30% of circulating IL-6 in humans. In analogy with leptin secretion, IL-6 production by adipose
Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6
Diabetes Research and Clinical Practice, 2005
Objective: To investigate the relationship between serum concentrations of the cytokines C-reactive protein (CRP), tumor necrosis factor (TNF)-a, and interleukin (IL)-6, and obesity and visceral adiposity. Methods: A cross-sectional study of 100 Korean adults free from pre-existing inflammatory disease or cancer was performed. Body mass index (BMI), waist circumference, and serum concentrations of CRP, TNF-a and IL-6 were measured. In 46 obese subjects, fat mass was assessed by bioimpedance analysis and abdominal fat distribution was determined by computerized tomography scan. Results: Overall, serum concentrations of CRP, TNF-a and IL-6 were significantly correlated with weight, BMI, waist circumference, hip circumference, and waist-hip ratio. In obese subjects, CRP and IL-6 were significantly correlated with BMI, waist circumference and visceral adipose tissue. Multiple regression analysis showed that CRP was significantly associated with BMI, whereas IL-6 was significantly related with visceral adiposity in obese subjects. Conclusions: The positive associations of obesity and visceral adiposity with elevated cytokine levels suggest the importance of reducing obesity and visceral adiposity to prevent elevations in cytokine levels.
Role of Serum Adiponectin, IL-6 and Hs CRP in Nonalcoholic Fatty Liver Egyptian Patients
Scientific Background: Non alcoholic fatty liver (NAFLD) is accumulation of fat in the liver cells of peoples who drink little or no alcohol causing mild steatosis with mostly no signs, symptoms or complication but this may progress to steatohepatitis (NASH) and may liver cirrhosis then failure. NAFLD is recognized as the most common type of chronic liver disease in Western countries and the leading cause of cryptogenic cirrhosis. Insulin resistance (IR) is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of IR or metabolic syndrome (MetS). Although the pathogenesis of NAFLD is not fully elucidated, a complex interaction between adipokines and cytokines produced by adipocytes and/or inflammatory cells infiltrating adipose tissue appears to play a crucial role in MetS and NAFLD and its progress. A number of factors are linked with NAFLD such as obesity, type 2 diabetis mellitus (T2DM), hyperlipidemia, gastric bypass, and its progress to NASH correlate with certain cytokines secreted like adiponectin, interlukin-6 (IL-6), and C- reactive protein CRP. Adiponectin is a novel adipocyte-specific protein, which, it has been suggested, plays a role in the development of insulin resistance and atherosclerosis. The role of (IL-6) in liver pathology is very complex, and its participation in the development of NAFLD remains unclear. IL-6 is a key element in the acute phase response, mediating the synthesis of several acute phase proteins (such as CRP and serum amyloid A). Thus, we cannot exclude the possibility that IL-6 might also play an indirect deleterious role in NAFLD pathogenesis. In diet-induced obese mice, treatment with IL-6 antibodies improved sensitivity to insulin. Objective: This study aim is to evaluate the level of adiponectin, IL-6 and CRP in Egyptian patients with NAFLD. Methods: This study was conducted on 2 groups 104 NAFLD as diagnosed by ultrasound examination and 21 healthy participants as control group. All the subjects were subjected to an abdominal ultrasonography, liver enzymes ALT & AST, lipid profile (triglycerides, HDL, LDL, cholesterol, CRP, IL-6 & Adiponectin). Results: Plasma adiponectin levels were significantly lower in NAFLD patients than control gp (3.05±2.65μg/ml vs 10.52±3.35 (μg/ml). IL-6 level was higher in NAFLD than control gp but not significant (114.24±22.32pg/ml vs 104.9±19.98pg/ml). CRP was significantly higher in NAFLD than control gp (17.86±11.59mg/L vs 5.4±3.81mg/L). Adiponectin ROC curve showed an AUROC curve in NAFLD gp (0.918 p=0.0001). IL-6 ROC curve showed an AUROC curve in NAFLD gp (0.703 p=0.0003). CRP ROC curve showed an AUROC curve in NAFLD gp (0.853 p=0.0001). Conclusion: Patients with NAFLD have lower adiponectin levels and higher IL-6 and CRP levels compared with their control group.
ADIPOCYTOKINES AND C-REACTIVE PROTEIN IN OBESITY
jmed.ro
Cardiovascular diseases represent the main cause of morbidity and mortality in overweight and obese patients. The atherosclerosis process represents the morphopathological substrate of these illnesses. The purpose of this study was to analyze the link between some specific adipocytokines (such as leptine) and some non-specific ones (such are IL-6, TNF-a), the insulin resistance, the reactive C protein, and the weight condition. The study group was homogenous as age and sex and consists of 30 persons (10 obese, 10 with overweight and 10 normoponderal). We found a strong direct correlation between the BMI and the leptine level (r=0.83), as well as between the insulin resistance (HOMAIR evaluated) and the abdominal circumference (r=0.90). PCRus, had a strong direct correlation with CT (r=0,82), LDLc (r=0,81) and BMI (r=0,79). At obese and overweight persons pro-inflammatory cytokines were increased, versus normoponderal people. That explains their increased cardiovascular risk. The levels of specific and non-specific adipocytokines, as well as the level of reactive C protein, were directly linked with the BMI and the abdominal circumference. As a clinical aspect, the abdominal circumference is the best indicator for insulin resistance.
PubMed, 2006
This study aimed to 1) compare levels of high sensitivity c-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) between overweight Thais and apparently healthy controls, and 2) investigate the association between serum hs-CRP, IL-6, and TNF-alpha levels and other biochemical parameters. A total of 180 health-conscious adults aged 25-60 years, who resided in Bangkok, participated in this study. No significant difference was found in age and sex between the overweight subjects and controls. Serum levels of hs-CRP, IL-6, TNF-alpha, glucose, lipid profile, body mass index (BMI), waist circumference (WC), hip circumference (HC) and waist hip ratio (WHR) were determined in these volunteers. The mean levels of white blood cells (WBC), uric acid, total cholesterol (TC), triglyceride (TG), and hs-CRP were significantly higher in the overweight subjects than those in the controls, whereas high density lipoprotein-cholesterol (HDL-C) values were significantly higher in the controls than the overweight subjects (p < 0.05). Hs-CRP levels were significantly positively correlated with levels of TG, BMI, WC, HC and WHR. HDL-C levels were significantly negative correlated with hs-CRP levels. In conclusion, the prevalence of elevated serum hs-CRP levels was higher in overweight subjects than controls. However, more data in larger and other population groups are needed to confirm this study.
The major inflammatory mediator interleukin-6 and obesity
Inflammation Research, 2009
Adipose tissue is one of the main sources of inflammatory mediators, with interleukin-6 (IL-6) among them. Although high systemic levels of inflammatory mediators are cachectogenic and/or anorexic, today it is a widely propagated thesis that in the background of obesity, a low level of chronic inflammation can be found, with IL-6 being one of the many suggested mediators. This paper reviews the studies describing elevated IL-6 levels in obese patients and the role of adipocytes and adipose-tissue macrophages in the production of IL-6. The secretion of IL-6 is regulated by several physiologic or pathologic factors: hormones, cytokines, diet, physical activity, stress, hypoxia, and others. Adipose tissue-derived IL-6 may have an effect on metabolism through several mechanisms, including adipose tissue-specific gene expression, triglyceride release, lipoprotein lipase downregulation, insulin sensitivity, and so on. Having a better understanding of these mechanisms may contribute to the prevention and treatment of obesity.
Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation
Translational Research, 2012
The mechanisms underlying the pathogenesis of obesity-related atherosclerosis remain to be clarified. To investigate the preclinical phase, interleukin-6 (IL-6) plasma levels were analyzed together with clinical, anthropometric, inflammatory, and metabolic variables in a well-defined cohort of 677 young and middle-aged overweight/obese and normal-weight subjects. In the juvenile and adult overweight/obese study group, IL-6 levels were increased significantly compared with normal-weight, age-matched controls (P , 0.001). In both juveniles and adults, higher levels of IL-6 were observed in obese compared with overweight participants. Subjects with metabolic syndrome (MS) had significantly higher IL-6 levels than those without MS. In juveniles, leptin, and in adults, the waist-to-height ratio, turned out to be the best predictor of IL-6 plasma levels in a multiple stepwise regression model. Taken together, in every age group, interleukin-6 is associated positively with the grade of overweight. Interestingly, leptin, which is the best known adipokine, is associated predictively with interleukin-6 plasma levels only in juveniles, which may indicate an important role of this molecule in the initiation of obesity-related inflammation. (Translational Research 2012;159:118-124) Abbreviations: ALT/GPT ¼ alanin-aminotransferase; BMI ¼ body mass index; CRP ¼ C-reactive protein; CT ¼ computed tomography; ELISA ¼ enzyme-linked immunosorbent assay; HDL ¼ high-density lipoprotein; HOMA-IR ¼ homeostatic model assessment-insulin resistance; IL-6 ¼ interleukin-6; IMT ¼ intima-media thickness; LDL ¼ low-density lipoprotein; oxLDL ¼ oxidized LDL; SAT ¼ subcutaneous adipose tissue; US-CRP ¼ ultrasensitive C-reactive protein; VAT ¼ visceral adipose tissue
Interleukin 6, Matrix Metalloproteinase-8 and Tissue Inhibitor-1 Levels in Obesity
Biomedical Journal of Scientific & Technical Research, 2020
Obesity is a nutritional disease characterized by excess of adipose tissue. It is recognized as a low-grade chronic inflammation state characterized by increased serum levels of acute phase proteins such as interleukins (ILs) and cytokines. IL-6 is a proinflammatory cytokine, which is involved in the regulation of lipid metabolism associated with obesity and inflammation. It plays numerous proinflammatory roles. However, IL-6 may also play an anti-inflammatory role. Matrix metalloproteinases (MMPs) participate in several physiological processes such as remodeling of extracellular matrix (ECM), healing, angiogenesis and apoptosis. They are regulated by specific tissue inhibitors (TIMPs) which block access to the active site of MMPs. A dual role for MMP-8 has been described under specific conditions: MMP-8 plays a role in the development of the inflammatory response but appears to play an anti-inflammatory role during recovery and may be crucial for this process. Aims: To determine the IL-6, MMP-8 and TIMP-1 levels and compare the results between 3 groups of individuals (between 26 and 65 years): normal weight (n=8), overweight (n=11) and obese (n=22). Material and Methods: The semi-quantification of IL-6, MMP-8 and TIMP-1 was performed through the slot blot technique. Results: The levels of MMP-8 and IL-6 were higher in the group of overweight individuals than in the normal weight group and in the obese group, but the differences were not statistically significant. TIMP-1 levels were slightly elevated in the group of normal weight individuals and in the group of obese individuals, in relation to the group of overweight individuals, however the differences were not statistically significant. There was also a moderate positive correlation between glycemic levels and the percentage of visceral fat mass (p<0.0001) and between serum levels of MMP-8 and serum levels of IL-6 (p<0.05). Discussion and Conclusion: The significant correlation between IL-6 levels and the percentage of visceral fat mass may be related to the fact that adipose tissue is endocrine and produce numerous factors contributing to systemic inflammation. The moderate positive correlation between serum MMP-8 levels and serum IL-6 levels may indicate that these can be stimulated by the same mechanisms in the inflammation process.