scholarly journals Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 730 ◽  
Author(s):  
Sardar Sindhu ◽  
Shihab Kochumon ◽  
Reeby Thomas ◽  
Abdullah Bennakhi ◽  
Fahd Al-Mulla ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Macrophage Polarization ◽  
High Density Lipoproteins ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Obese Patients ◽  
C Reactive Protein ◽  
Metabolic Inflammation ◽  
Reactive Protein

Interferon regulatory factors (IRFs) are emerging as the metabolic transcriptional regulators in obesity/type-2 diabetes (T2D). IRF5 is implicated with macrophage polarization toward the inflammatory M1-phenotype, nonetheless, changes in the adipose expression of IRF5 in T2D and relationship of these changes with other markers of adipose inflammation remain unclear. Therefore, we determined the IRF5 gene expression in subcutaneous adipose tissue samples from 46 T2D patients including 35 obese (Body Mass Index/BMI 33.83 ± 0.42 kg/m2) and 11 lean/overweight individuals (BMI 27.55 ± 0.46 kg/m2) using real-time qRT-PCR. IRF5 protein expression was assessed using immunohistochemistry and confocal microscopy. Fasting plasma glucose, insulin, HbA1c, C-reactive protein, cholesterol, low- and high-density lipoproteins (LDL/HDL), and triglycerides were measured using commercial kits. IRF5 gene expression was compared with that of signature inflammatory markers and several clinico-metabolic indicators. The data (mean ± SEM) show the enhanced adipose IRF5 gene (p = 0.03) and protein (p = 0.05) expression in obese compared to lean/overweight diabetic patients. Adipose IRF5 transcripts in diabetic obese individuals associated positively with those of TNF-α, IL-18, IL-23A, CXCL8, CCL2, CCL7, CCR1/5, CD11c, CD68, CD86, TLR4/7/10, Dectin-1, FGL-2, MyD88, NF-κB, IRF3, and AML1 (p < 0.05). In diabetic lean/overweight subjects, IRF5 expression associated with BMI, body fat %age, glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR, C-reactive protein (CRP), IL-5, and IL-1RL1 expression; while in all T2D patients, IRF5 expression correlated with that of IRF4, TLR2/8, and CD163. In conclusion, upregulated adipose tissue IRF5 expression in diabetic obese patients concurs with the inflammatory signatures and it may represent a potential marker for metabolic inflammation in obesity/T2D.

Nutrient-Adjusted High-Fat Diet is Associated with Absence of Periepididymal Adipose Tissue Inflammation: Is there a Link with Adequate Micronutrient Levels?

2013 ◽  
Vol 83 (5) ◽  
pp. 299-310 ◽  
Author(s):  
Monica Yamada ◽  
Marina Maintinguer Norde ◽  
Maria C. Borges ◽  
Tatiane Mieko de Meneses Fujii ◽  
Patrícia Silva Jacob ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Adipose Tissue Inflammation ◽  
C Reactive Protein ◽  
High Fat ◽  
Tissue Inflammation ◽  
Reactive Protein ◽  
Tnf Α

The aim of this study was to investigate the real impact of dietary lipids on metabolic and inflammatory response in rat white adipose tissue. Male healthy Wistar rats were fed ad libitum with a control diet (CON, n=12) or with an adjusted high-fat diet (HFD, n=12) for 12 weeks. Oral glucose and insulin tolerance tests were performed during the last week of the protocol. Plasma fatty acid, lipid profile, body adiposity, and carcass chemical composition were analyzed. Plasma concentration of leptin, adiponectin, C-reactive protein (CRP), TNF-α, IL-6, and monocyte chemotactic protein (MCP-1) was measured. Periepididymal adipose tissue was employed to evaluate TNF-α, MCP-1, and adiponectin gene expression as well as NF-κB pathway and AKT proteins. Isocaloric intake of the adjusted HFD did not induce hyperphagia, but promoted an increase in periepididymal (HFD = 2.94 ± 0.77 vs. CON = 1.99 ± 0.26 g/100 g body weight, p = 0.01) and retroperitoneal adiposity (HFD = 3.11 ± 0.81 vs. CON = 2.08 ± 0.39 g/100 g body weight, p = 0.01) and total body lipid content (HFD = 105.3 ± 20.8 vs. CON = 80.5 ± 7.6 g carcass, p = 0.03). Compared with control rats, HFD rats developed glucose intolerance (p=0.01), dyslipidemia (p = 0.02) and exhibited higher C-reactive protein levels in response to the HFD (HFD = 1002 ± 168 vs. CON = 611 ± 260 ng/mL, p = 0.01). The adjusted HFD did not affect adipokine gene expression or proteins involved in inflammatory signaling, but decreased AKT phosphorylation after insulin stimulation in periepididymal adipose tissue (p = 0.01). In this study, nutrient-adjusted HFD did not induce periepididymal adipose tissue inflammation in rats, suggesting that the composition of HFD differently modulates inflammation in rats, and adequate micronutrient levels may also influence inflammatory pathways.

scholarly journals Plasma Osteopontin Increases After Bariatric Surgery and Correlates with Markers of Bone Turnover But Not with Insulin Resistance

2008 ◽  
Vol 93 (6) ◽  
pp. 2307-2312 ◽  
Author(s):  
Michaela Riedl ◽  
Greisa Vila ◽  
Christina Maier ◽  
Ammon Handisurya ◽  
Soheila Shakeri-Manesch ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bariatric Surgery ◽  
Resistance Index ◽  
Model Assessment ◽  
Obese Patients ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Insulin Resistance Index ◽  
Homeostatic Model Assessment ◽  
Homeostatic Model

Abstract Context: Osteopontin (OPN) is a multifunctional protein involved in bone metabolism, cardiovascular disease, diabetes, and obesity. OPN levels are elevated in the plasma and adipose tissue of obese subjects, and are decreased with diet-induced weight loss. Objective: We investigated the effect of bariatric surgery on plasma OPN concentrations in morbidly obese patients. Setting: The study was performed at a university hospital. Subjects: We investigated 40 obese patients aged 43.1 ± 1.8 yr, scheduled to undergo bariatric surgery. Roux-en-Y gastric bypass (RYGB) was performed in 30 subjects (27 females, three males), and laparoscopic adjustable gastric banding (LAGB) in 10 subjects (eight females, two males). Study Design: All patients were studied before and 1 yr (10.3–14.8 months) after the intervention. Main Outcome Measures: OPN, leptin, C-reactive protein, insulin, the homeostatic model assessment insulin resistance index, calcium, 25-hydroxyvitamin D, C telopeptide, and osteocalcin were determined. Results: Both bariatric procedures significantly reduced body weight, body mass index, insulin, leptin, and C-reactive protein 1 yr after surgery. Plasma OPN increased from 31.4 ± 3.8 to 52.8 ± 3.7 ng/ml after RYGB (P &lt; 0.001) and from 29.8 ± 6.9 to 46.4 ± 10.6 ng/ml after LAGB (P = 0.042). Preoperative OPN correlated with age, insulin, the homeostatic model assessment insulin resistance index, and postoperative OPN. Postoperative OPN correlated with C telopeptide and osteocalcin. Conclusions: One year after RYGB and LAGB, plasma OPN levels significantly increased and correlated with biomarkers of bone turnover. Unlike other proinflammatory cytokines, OPN does not normalize but increases further after bariatric surgery.

scholarly journals Adipose tissue gene expression of CXCL10 and CXCL11 modulates inflammatory markers in obesity: implications for metabolic inflammation and insulin resistance

2020 ◽  
Vol 11 ◽  
pp. 204201882093090
Author(s):  
Shihab Kochumon ◽  
Ashraf Al Madhoun ◽  
Fatema Al-Rashed ◽  
Rafaat Azim ◽  
Ebaa Al-Ozairi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Inflammatory Markers ◽  
Fasting Blood Glucose ◽  
Subcutaneous Fat ◽  
Family Members ◽  
Enzyme Linked Immunosorbent Assay ◽  
Model Assessment ◽  
Metabolic Inflammation

Background: The CXCL subfamily of chemokines (CXCL9, CXCL10, and CXCL11; angiostatic chemokines) plays a key role in many inflammatory diseases. However, the expression of CXCLs in adipose tissue (AT) during obesity and association of these CXCLs with inflammatory markers and insulin resistance are poorly understood. Therefore, this study aimed to investigate the effects of CXCL gene expression on subcutaneous AT inflammatory markers and insulin resistance. Methods: Subcutaneous-fat biopsies were collected from 59 nondiabetic (lean/overweight/obese) individuals for RNA isolation. Expression levels of AT CXCL and inflammatory markers were determined by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). Biomedical parameters in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). Insulin resistance was estimated using homeostatic model assessment (HOMA-IR). Results: AT CXCL expression was higher in obese compared with lean individuals ( p < 0.05) and positively correlated with body mass index (BMI; r ⩾ 0.269, p < 0.05). Expression of CXCL9, CXCL10, and CXCL11 correlated significantly with various pro-inflammatory markers, including family members of interleukins, chemokines, and their prospective receptors ( r ⩾ 0.339, p ⩽ 0.009), but not anti-inflammatory markers. CXCL11 expression correlated specifically with the expression of CCL5, CCL18, TLR3, TLR4, TLR8, IRF5, and NF-κB ( r ⩾ 0.279, p ⩽ 0.039). Notably, CXCL11 was correlated with C-reactive protein (CRP), fasting blood glucose (FBG), and HOMA-IR. In multiple regression analysis, CXCL11 was identified as an independent predictor of CCL19, CCL5, IL-6, and TLR3. Conclusion: These data suggest that the CXCL family members, specifically CXCL10 and CXCL11, are potential biomarkers for the onset of AT inflammation during obesity.

scholarly journals Increased Adipose Tissue Expression of Interferon Regulatory Factor (IRF)-5 in Obesity: Association with Metabolic Inflammation

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1418 ◽  
Author(s):  
Sardar Sindhu ◽  
Reeby Thomas ◽  
Shihab Kochumon ◽  
Ajit Wilson ◽  
Mohamed Abu-Farha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Macrophage Polarization ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Metabolic Inflammation ◽  
M1 Macrophage ◽  
Gene And Protein Expression ◽  
Local Expression

Interferon regulatory factor (IRF)-5 is known to be involved in M1 macrophage polarization, however, changes in the adipose expression of IRF5 in obesity and their relationship with the local expression of proinflammatory cytokines/chemokines are unknown. Therefore, IRF5 gene expression was determined in the subcutaneous adipose tissue samples from 53 non-diabetic individuals (6 lean, 18 overweight, and 29 obese), using real-time RT-PCR. IRF5 protein expression was also assessed using immunohistochemistry and/or confocal microscopy. Adipose gene expression of signature immune metabolic markers was also determined and compared with adipose IRF5 gene expression. Systemic levels of C-reactive protein and adiponectin were measured by ELISA. The data show that adipose IRF5 gene (P = 0.008) and protein (P = 0.004) expression was upregulated in obese compared with lean individuals. IRF5 expression changes correlated positively with body mass index (BMI; r = 0.37/P = 0.008) and body fat percentage (r = 0.51/P = 0.0004). In obese, IRF5 changes associated positively with HbA1c (r = 0.41/P = 0.02). A good agreement was found between gene and protein expression of IRF5 in obese subjects (r = 0.65/P = 0.001). IRF5 gene expression associated positively with adipose inflammatory signatures including local expression of TNF-α, IL-6, CXCL8, CCL-2/5, IL-1β, IL-18, CXCL-9/10, CCL7, CCR-1/2/5, TLR-2/7/8/9, IRF3, MyD88, IRAK-1, and inflammatory macrophage markers (P < 0.05). Interestingly, IRF5 gene expression correlated positively with CRP (r = 0.37, P = 0.03) and negatively with adiponectin levels (r = −0.43, P = 0.009). In conclusion, elevated adipose IRF5 expression in obesity concurs with the typical inflammatory signatures, locally and systemically. Hence, the IRF5 upregulation may represent a novel adipose tissue marker for metabolic inflammation.

Inflammation may modulate IL-6 and C-reactive protein gene expression in the adipose tissue: the role of IL-6 cell membrane receptor

2007 ◽  
Vol 293 (4) ◽  
pp. E1030-E1035 ◽  
Author(s):  
Bruno Memoli ◽  
Alfredo Procino ◽  
Paolo Calabrò ◽  
Pasquale Esposito ◽  
Giuseppe Grandaliano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Real Time ◽  
Inflammatory Disease ◽  
Stromal Cells ◽  
Real Time Pcr ◽  
Healthy Controls ◽  
C Reactive Protein ◽  
Reactive Protein

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.

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