Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes

2007 ◽  
Vol 292 (3) ◽  
pp. E740-E747 ◽  
Author(s):  
S. J. Creely ◽  
P. G. McTernan ◽  
C. M. Kusminski ◽  
ff. M. Fisher ◽  
N. F. Da Silva ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Serum Insulin ◽  
Human Adipose Tissue ◽  
Innate Immune ◽  
System Response ◽  
Low Grade ◽  
Tnf Α

Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-κB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold ( P < 0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-α and IL-6 secretion (IL-6, Control: 2.7 ± 0.5 vs. LPS: 4.8 ± 0.3 ng/ml; P < 0.001; TNF-α, Control: 1.0 ± 0.83 vs. LPS: 32.8 ± 6.23 pg/ml; P < 0.001). NF-κB inhibitor reduced IL-6 in AbdSc adipocytes (Control: 2.7 ± 0.5 vs. NF-κB inhibitor: 2.1 ± 0.4 ng/ml; P < 0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-κB was increased in T2DM patients ( P < 0.05), and TLR-2, TRAF-6, and NF-κB were increased in LPS-treated adipocytes ( P < 0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls ( r = 0.678, P < 0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P = 0.0395) and serum LPS (reduced by 35%, P = 0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.

scholarly journals Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

2018 ◽  
Vol 45 (2) ◽  
pp. 572-590 ◽  
Author(s):  
Sardar Sindhu ◽  
Nadeem Akhter ◽  
Shihab Kochumon ◽  
Reeby Thomas ◽  
Ajit Wilson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Mapk Signaling ◽  
Innate Immune ◽  
Low Grade ◽  
Sod Activity ◽  
Metabolic Inflammation

Background/Aims: Metabolic diseases such as obesity and type-2 diabetes (T2D) are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. Methods: TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC), or primary monocytes were treated with hydrogen peroxide (H2O2) for induction of reactive oxygen species (ROS)-mediated oxidative stress. Superoxide dismutase (SOD) activity was measured using a commercial kit. Data (mean±SEM) were compared using unpaired student’s t-test and P<0.05 was considered significant. Results: The adipose tissue TLR10 gene/protein expression was found to be significantly upregulated in obesity as well as T2D which correlated with body mass index (BMI). ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB)/mitogen activated protein kinase (MAPK) signaling as well as endoplasmic reticulum (ER) stress. H2O2-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Conclusion: Oxidative stress induces the expression of TLR10 which may represent an immune marker for metabolic inflammation.

scholarly journals PO-294 Effects of HIIT on FTO protein expression and its relationship with glucose and fat metabolism

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Chunyan Xu ◽  
Juan Zhao ◽  
Jiayan Duan
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Blood Glucose ◽  
Protein Expression ◽  
Oxidation Rate ◽  
Serum Insulin ◽  
Fat Metabolism

Objective FTO (Fat mass and obesity-associated) is associated with increased risk of obesity and type 2 diabetes incurrence. Studies have shown that the expression of FTO protein in skeletal muscle and adipose tissue is related to the oxidation rate of whole body substrate. With the increase of age, the body's carbohydrate oxidation rate decreases, the fat oxidation rate increases, and at the meanwhile the expression of FTO protein in skeletal muscle decreases and that in adipose increases. HIIT is very helpful for inhibiting obesity, insulin resistance and type 2 diabetes. So the purpose of this study is to investigate the effect of HIIT exercise on the expression of FTO protein in rats and its relationship to glucose and fat metabolism. Methods 20 Male, 3-week-old SD rats were randomly divided into two groups, each group has 10 rats. C group: sedentary; HIIT group: high-intensity intermittent training group (85% ~ 90% VO2max exercise for 6min, 50% VO2max exercise interval 4min, repeated 6 times. 5 times/week ,4 weeks). All subjects were maintained in a free facility with constant temperature of 25°C, light-dark cycle of 12/12 h and free access to water. 48 hours after the last exercise, all samples were taken with an overnight fast. The expression of FTO protein in skeletal muscle and adipose tissue was measured by Western Blot. Serum insulin was tested by ELISA; Estimation of blood glucose was tested by Glucose oxidase method. Results 1.The expression of FTO protein in skeletal muscle was significantly higher than that of group C (P <0.01); The expression of FTO protein in adipose tissue of HIIT group was significantly lower than that of group C (P <0.05); 2. Serum insulin levels of group HIIT was significantly lower than that of group C (p <0.01); And the blood glucose of group HIIT was significantly lower than that of group C (p <0.01). 3. Serum LDL-C of group HIIT was significantly lower than that of group C (p <0.01), and serum HDL-C of group HIIT was significantly higher than that of group C (p <0.01);4. Correlation analysis showed that serum insulin level was negatively correlated with skeletal muscle FTO protein expression (R = -0.454, p < 0.05). Correlation analysis showed that serum LDL-C levels was positively correlated with adipose tissue FTO protein expression (R=0.559, p < 0.05) and serum HDL-C levels was negatively correlated with adipose tissue FTO protein expression (R=-0.474, p < 0.05). Conclusions 1. HIIT can increase the protein expression of FTO in rat skeletal muscle and decrease the expression of FTO protein in adipose tissue; 2. HIIT can regulate glucose metabolism and lipid metabolism in rats; 3. The regulation of glucose metabolism by HIIT may be related to the increase of FTO protein expression in skeletal muscle. The regulation of lipid metabolism may be related to the reduction of FTO protein expression in adipose tissue.

1973-P: Single-Nuclei Transcriptomics of Human Adipose Tissue Identify Distinct Adipocyte Progenitor Subpopulations in Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1973-P
Author(s):  
CLARISSA STRIEDER-BARBOZA ◽  
CARMEN G. FLESHER ◽  
LYNN M. GELETKA ◽  
ROBERT W. OROURKE ◽  
CAREY N. LUMENG
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Human Adipose Tissue

scholarly journals T Cell–Derived IL-22 Amplifies IL-1β–Driven Inflammation in Human Adipose Tissue: Relevance to Obesity and Type 2 Diabetes

Diabetes ◽  
2014 ◽  
Vol 63 (6) ◽  
pp. 1966-1977 ◽  
Author(s):  
Elise Dalmas ◽  
Nicolas Venteclef ◽  
Charles Caer ◽  
Christine Poitou ◽  
Isabelle Cremer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
T Cell ◽  
Human Adipose Tissue

IL-6 as a Surrogate Biomarker: The IL-6 Clinical Value for the Diagnosis of Insulin Resistance and Type 2 Diabetes.

2021 ◽  
pp. 1-13
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Diagnostic Value ◽  
Low Grade ◽  
Clinical Value ◽  
Insulin Resistant ◽  
Tnf Α ◽  
Low Grade Inflammation

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus (T2D). It occurs as a result of lipid disorders and increased levels of circulating free fatty acids (FFAs). FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased levels fatty acid has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes. Among the biomarkers that are accompanying low grade inflammation include IL-1β, IL-6 and TNF-α. The current review point out the importance of measuring the inflammatory biomarkers especially focusing on the conductance and measurement for IL-6 as a screening laboratory test and its diagnostic value in clinical practice.

scholarly journals Peroxisome Proliferator-Activated Receptor γ and Adipose Tissue—Understanding Obesity-Related Changes in Regulation of Lipid and Glucose Metabolism

2006 ◽  
Vol 92 (2) ◽  
pp. 386-395 ◽  
Author(s):  
Arya M. Sharma ◽  
Bart Staels
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Endocrine Function ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Abstract Context: Adipose tissue is a metabolically dynamic organ, serving as a buffer to control fatty acid flux and a regulator of endocrine function. In obese subjects, and those with type 2 diabetes or the metabolic syndrome, adipose tissue function is altered (i.e. adipocytes display morphological differences alongside aberrant endocrine and metabolic function and low-grade inflammation). Evidence Acquisition: Articles on the role of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue of healthy individuals and those with obesity, metabolic syndrome, or type 2 diabetes were sourced using MEDLINE (1990–2006). Evidence Synthesis: Articles were assessed to provide a comprehensive overview of how PPARγ-activating ligands improve adipose tissue function, and how this links to improvements in insulin resistance and the progression to type 2 diabetes and atherosclerosis. Conclusions: PPARγ is highly expressed in adipose tissue, where its activation with thiazolidinediones alters fat topography and adipocyte phenotype and up-regulates genes involved in fatty acid metabolism and triglyceride storage. Furthermore, PPARγ activation is associated with potentially beneficial effects on the expression and secretion of a range of factors, including adiponectin, resistin, IL-6, TNFα, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and angiotensinogen, as well as a reduction in plasma nonesterified fatty acid supply. The effects of PPARγ also extend to macrophages, where they suppress production of inflammatory mediators. As such, PPARγ activation appears to have a beneficial effect on the relationship between the macrophage and adipocyte that is distorted in obesity. Thus, PPARγ-activating ligands improve adipose tissue function and may have a role in preventing progression of insulin resistance to diabetes and endothelial dysfunction to atherosclerosis.

scholarly journals Dendritic Cells in Subcutaneous and Epicardial Adipose Tissue of Subjects with Type 2 Diabetes, Obesity, and Coronary Artery Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Miloš Mráz ◽  
Anna Cinkajzlová ◽  
Jana Kloučková ◽  
Zdeňka Lacinová ◽  
Helena Kratochvílová ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Dendritic Cells ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Epicardial Adipose Tissue ◽  
Low Grade ◽  
Elective Cardiac Surgery ◽  
Artery Disease

Dendritic cells (DCs) are professional antigen-presenting cells contributing to regulation of lymphocyte immune response. DCs are divided into two subtypes: CD11c-positive conventional or myeloid (cDCs) and CD123-positive plasmacytoid (pDCs) DCs. The aim of the study was to assess DCs (HLA-DR+ lineage-) and their subtypes by flow cytometry in peripheral blood and subcutaneous (SAT) and epicardial (EAT) adipose tissue in subjects with (T2DM, n=12) and without (non-T2DM, n=17) type 2 diabetes mellitus undergoing elective cardiac surgery. Subjects with T2DM had higher fasting glycemia (8.6±0.7 vs. 5.8±0.2 mmol/l, p<0.001) and glycated hemoglobin (52.0±3.4 vs. 36.9±1.0 mmol/mol, p<0.001) and tended to have more pronounced inflammation (hsCRP: 9.8±3.1 vs. 5.1±1.9 mg/ml, p=0.177) compared with subjects without T2DM. T2DM was associated with reduced total DCs in SAT (1.57±0.65 vs. 4.45±1.56% for T2DM vs. non-T2DM, p=0.041) with a similar, albeit insignificant, trend in EAT (0.996±0.33 vs. 2.46±0.78% for T2DM vs. non-T2DM, p=0.171). When analyzing DC subsets, no difference in cDCs was seen between any of the studied groups or adipose tissue pools. In contrast, pDCs were increased in both SAT (13.5±2.0 vs. 4.6±1.9% of DC cells, p=0.005) and EAT (29.1±8.7 vs. 8.4±2.4% of DC, p=0.045) of T2DM relative to non-T2DM subjects as well as in EAT of the T2DM group compared with corresponding SAT (29.1±8.7 vs. 13.5±2.0% of DC, p=0.020). Neither obesity nor coronary artery disease (CAD) significantly influenced the number of total, cDC, or pDC in SAT or EAT according to multiple regression analysis. In summary, T2DM decreased the amount of total dendritic cells in subcutaneous adipose tissue and increased plasmacytoid dendritic cells in subcutaneous and even more in epicardial adipose tissue. These findings suggest a potential role of pDCs in the development of T2DM-associated adipose tissue low-grade inflammation.

Secretion of neuropeptide Y in human adipose tissue and its role in maintenance of adipose tissue mass

2007 ◽  
Vol 293 (5) ◽  
pp. E1335-E1340 ◽  
Author(s):  
Katarina Kos ◽  
Alison L. Harte ◽  
Sean James ◽  
David R. Snead ◽  
Joseph P. O'Hare ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Elective Surgery ◽  
Ex Vivo ◽  
Human Adipose Tissue ◽  
Tissue Mass ◽  
Paracrine Effects ◽  
Tnf Α ◽  
Adiposity Signals

NPY is an important central orexigenic hormone, but little is known about its peripheral actions in human adipose tissue (AT) or its potential paracrine effects. Our objective was to examine NPY's role in AT, specifically addressing NPY protein expression, the effect of NPY on adipokine secretion, and the influence of insulin and rosiglitazone (RSG) on adipocyte-derived NPY in vitro. Ex vivo human AT was obtained from women undergoing elective surgery [age: 42.7 ± 1.5 yr (mean ± SE), BMI: 26.2 ± 0.7 kg/m2; n = 38]. Western blot analysis was used to determine NPY protein expression in AT depots. Abdominal subcutaneous (AbSc) adipocytes were isolated and treated with recombinant (rh) NPY, insulin, and RSG. NPY and adipokine levels were measured by ELISA. Our results were that NPY was localized in human AT and adipocytes and confirmed by immunohistochemistry. Depot-specific NPY expression was noted as highest in AbSc AT (1.87 ± 0.23 ODU) compared with omental (Om; 1.03 ± 0.15 ODU, P = 0.029) or thigh AT (Th; 1.0 ± 0.29 ODU, P = 0.035). Insulin increased NPY secretion (control: 0.22 ± 0.024 ng/ml; 1 nM insulin: 0.26 ± 0.05 ng/ml; 100 nM insulin: 0.29 ± 0.04 ng/ml; 1,000 nM insulin: 0.3 ± 0.04 ng/ml; P < 0.05, n = 13), but cotreatment of RSG (10 nM) with insulin (100 nM) had no effect on NPY secretion. Furthermore, adipocyte treatment with rh-NPY downregulated leptin secretion (control: 6.99 ± 0.89 ng/ml; 1 nmol/l rh-NPY: 4.4 ± 0.64 ng/ml; 10 nmol/l rh-NPY: 4.3 ± 0.61 ng/ml, 100 nmol/l rh-NPY: 4.2 ± 0.67 ng/ml; P < 0.05, n = 10) but had no effect on adiponectin or TNF-α secretion. We conclude that NPY is expressed and secreted by human adipocytes. NPY secretion is stimulated by insulin, but this increment was limited by cotreatment with RSG. NPY's antilipolytic action may promote an increase in adipocyte size in hyperinsulinemic conditions. Adipose-derived NPY mediates reduction of leptin secretion and may have implications for central feedback of adiposity signals.

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