BACKGROUND AND AIMS: Macrophages are linked to the initiation of the chronic inflammation believed to underlie the changes taking place in the white fatty tissue of obese people. Both the number of macrophages, but their functional status, play an important role in the development of inflammation. Classically, macrophages are divided into two types: pro-inflammatory (M1) and anti-inflammatory (M2) types, and based on current immunological studies, further views on the functional distribution of macrophages are suggested. In this study, we evaluated the M1 and M2 macrophages ratio in obese subjects with, or without diabetes. To identify all macrophages, we used CD68 expression, while CD204 expression is typically used for the M2 macrophage. MATERIALS AND METHODS: During bariatric surgery, carried out in obese people with and without type 2 diabetes (T2D), we obtained subcutaneous adipose tissue from the navel and omental adipose tissue. We also obtained the same tissue from people with a physiological range of BMI from a judicial autopsy. Applying immunohistochemical staining anti-CD68 and anti-CD204, we carried out a quantitative evaluation of the number of macrophages. RESULTS: We found CD68+ and CD204+ positive macrophages in perivascular spaces and between fat cells, both isolated and in larger infiltrates. They were also present in so-called "crown-like structures" (CLS) around dying adipocytes. Quantitative analysis showed an increased number of macrophages in all obese patients compared to the control group of non-obese, individuals without T2D. The most striking observation was the macrophage increase in the visceral fatty tissue of diabetics. The number of CD68 and CD204 positive macrophages was statistically significantly smaller in patients without T2D. CONCLUSION: We demonstrated a significantly greater number of macrophages in visceral adipose tissue, especially in patients with T2D. Our results also show a positive correlation between the presence of T2D and the total number of macrophages; a significantly greater number of macrophages were found in visceral adipose tissue, especially in patients with T2D.
- MeSH
- antigeny diferenciační myelomonocytární MeSH
- bariatrická chirurgie MeSH
- bílá tuková tkáň imunologie patologie MeSH
- CD antigeny MeSH
- diabetes mellitus 2. typu imunologie MeSH
- dospělí MeSH
- imunofenotypizace MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy imunologie patologie MeSH
- mladý dospělý MeSH
- nitrobřišní tuk imunologie patologie MeSH
- obezita imunologie patologie chirurgie MeSH
- omentum MeSH
- podkožní tuk imunologie patologie MeSH
- scavengerové receptory - třída A MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: CD68+ cells are a potent source of inflammatory cytokines in adipose tissue and myocardium. The development of low-grade inflammation in adipose tissue is implicated in the pathogenesis of obesity-associated disorders including type 2 diabetes mellitus (T2DM) and cardiovascular disease. The main aim of the study was to characterize and quantify myocardial and adipose tissue CD68+ cells and adipose tissue crown-like structures (CLS) in patients with obesity, coronary artery disease (CAD) and T2DM. METHODS AND RESULTS: Samples were obtained from the right atrium, epicardial (EAT) and subcutaneous adipose tissue (SAT) during elective heart surgery (non-obese, n = 34 patients; obese, n = 24 patients). Immunohistochemistry was used to visualize CD68+ cells. M1-polarized macrophages were visualized by immunohistochemical detection of CD11c. The proportion of CD68+ cells was higher in EAT than in SAT (43.4 ± 25.0 versus 32.5 ± 23.1 cells per 1 mm2; p = 0.015). Myocardial CD68+ cells were more abundant in obese patients (45.6 ± 24.5 versus 27.7 ± 14.8 cells per 1 mm2; p = 0.045). In SAT, CD68+ cells were more frequent in CAD patients (37.3 ± 23.0 versus 23.1 ± 20.9 cells per 1 mm2; p = 0.012). Patients having CLS in their SAT had higher average BMI (34.1 ± 6.4 versus 29.0 ± 4.5; p = 0.024). CONCLUSIONS: Regional-based increases in the frequency of CD68+ cells and changes of their phenotype in CLS were detected in obese patients and CAD patients. Therapeutic modulation of adipose tissue inflammation may represent a target for treatment of obesity.
- MeSH
- antigeny CD11c analýza MeSH
- antigeny diferenciační myelomonocytární analýza MeSH
- biologické markery analýza MeSH
- CD antigeny analýza MeSH
- diabetes mellitus 2. typu imunologie patologie MeSH
- dospělí MeSH
- fenotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy imunologie patologie MeSH
- myokard imunologie patologie MeSH
- nemoci koronárních tepen imunologie patologie MeSH
- obezita imunologie patologie MeSH
- počet buněk MeSH
- podkožní tuk imunologie patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- zánět imunologie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
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.
- MeSH
- dendritické buňky metabolismus MeSH
- diabetes mellitus 2. typu imunologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci koronárních tepen imunologie metabolismus MeSH
- obezita imunologie metabolismus MeSH
- perikard imunologie metabolismus MeSH
- podkožní tuk imunologie metabolismus MeSH
- senioři MeSH
- tuková tkáň imunologie metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Immunocompetent cells including lymphocytes play a key role in the development of adipose tissue inflammation and obesity-related cardiovascular complications. The aim of the study was to explore the relationship between epicardial adipose tissue lymphocytes and coronary artery disease (CAD). To this end, we studied the content and phenotype of lymphocytes in peripheral blood, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT) in subjects with and without CAD undergoing elective cardiac surgery. Eleven subjects without CAD (non-CAD group) and 22 age-, BMI-, and HbA1C-matched individuals with CAD were included into the study. Blood, SAT, and EAT samples were obtained at the beginning of surgery. Lymphocyte populations were quantified as % of CD45+ cells using flow cytometry. Subjects with CAD had a higher total lymphocyte amount in EAT compared with SAT (32.24 ± 7.45 vs. 11.22 ± 1.34%, p = 0.025) with a similar trend observed in non-CAD subjects (29.68 ± 7.61 vs. 10.13 ± 2.01%, p = 0.067). T (CD3+) cells were increased (75.33 ± 2.18 vs. 65.24 ± 4.49%, p = 0.032) and CD3- cells decreased (21.17 ± 2.26 vs. 31.64 ± 4.40%, p = 0.028) in EAT of CAD relative to the non-CAD group. In both groups, EAT showed an elevated percentage of B cells (5.22 ± 2.43 vs. 0.96 ± 0.21%, p = 0.039 for CAD and 12.49 ± 5.83 vs. 1.16 ± 0.19%, p = 0.016 for non-CAD) and reduced natural killer (NK) cells (5.96 ± 1.32 vs. 13.22 ± 2.10%, p = 0.012 for CAD and 5.32 ± 1.97 vs. 13.81 ± 2.72%, p = 0.022 for non-CAD) relative to SAT. In conclusion, epicardial adipose tissue in subjects with CAD shows an increased amount of T lymphocytes relative to non-CAD individuals as well as a higher number of total and B lymphocytes and reduced NK cells as compared with corresponding SAT. These changes could contribute to the development of local inflammation and coronary atherosclerosis.
- MeSH
- B-lymfocyty MeSH
- imunohistochemie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci koronárních tepen krev imunologie metabolismus MeSH
- perikard imunologie metabolismus MeSH
- podkožní tuk imunologie metabolismus MeSH
- průtoková cytometrie MeSH
- senioři MeSH
- T-lymfocyty imunologie metabolismus MeSH
- tuková tkáň imunologie metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- diabetes mellitus 2. typu * farmakoterapie imunologie krev MeSH
- hmotnostní přírůstek * imunologie účinky léků MeSH
- inzulin * analogy a deriváty terapeutické užití MeSH
- krevní glukóza * metabolismus MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- podkožní tuk * imunologie MeSH
- tělesná hmotnost MeSH
- zánět imunologie MeSH
- Check Tag
- lidé MeSH
CONTEXT: It is not known whether biological differences reported between sc adipose tissue (SAT) and visceral adipose tissue (VAT) depots underlie the pathogenicity of visceral fat. OBJECTIVE: We compared SAT and VAT gene expression according to obesity, visceral fat accumulation, insulin resistance, and presence of the metabolic syndrome. DESIGN: Subjects were assigned into four groups (lean, overweight, obese, and obese with metabolic syndrome). SETTING: Subjects were recruited at a university hospital. PATIENTS: Thirty-two women were included. MAIN OUTCOME MEASURES: Anthropometric measurements, euglycemic-hyperinsulinemic clamps, blood analyses, and computed tomography scans were performed, and paired samples of SAT and VAT were obtained for DNA microarray-based gene expression profiling. RESULTS: Considering the two fat depots together, 1125 genes were more and 1025 genes were less expressed in lean compared with metabolic syndrome subjects. Functional annotation clustering showed, from lean to metabolic syndrome subjects, progressive down-regulation of metabolic pathways including branched-chain amino acid, fatty acid, carbohydrate, and mitochondrial energy metabolism and up-regulation of immune response genes involved in toll-like receptor, TNF, nuclear factor-κB, and apoptosis pathways. Metabolism and immune response genes showed an opposite correlation with fat mass, fat distribution, or insulin resistance indices. These associations were similar in SAT and VAT, although about 1000 genes showed differential expression between SAT and VAT. CONCLUSIONS: The increase in adiposity and the worsening of metabolic status are associated with a coordinated down-regulation of metabolism-related and up-regulation of immune response-related gene expression. Molecular adaptations in SAT prove as discriminating as those in VAT.
- MeSH
- dospělí MeSH
- down regulace MeSH
- exprese genu imunologie MeSH
- glykemický clamp MeSH
- inzulinová rezistence MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom genetika imunologie metabolismus MeSH
- nitrobřišní tuk imunologie metabolismus MeSH
- obezita genetika imunologie metabolismus MeSH
- podkožní tuk imunologie metabolismus MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: To study the influence of chronic malnutrition in patients with anorexia nervosa on endocrine function of adipose tissue on both circulating and subcutaneous fat mRNA expression level. PATIENTS AND DESIGN: A total of 12 patients with anorexia nervosa and 18 normal weight age-matched women underwent anthropometric examination, single blood drawing and subcutaneous adipose tissue biopsy. MEASUREMENTS: Serum concentrations of high-sensitive CRP (hsCRP), leptin, soluble leptin receptor, adiponectin, resistin, interleukin-6 and insulin were measured by Luminex, enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) kits. Subcutaneous adipose tissue mRNA expression of the same adipokines, adiponectin receptors 1 and 2 and immunocompetent cells marker CD68 was measured by real-time polymerase chain reaction (PCR). RESULTS: Decreased body fat content of patients with anorexia nervosa was accompanied by reduced hsCRP, leptin and increased adiponectin and soluble leptin receptor. Resistin, interleukin-6 and insulin levels did not differ from those of the control group. Fat mRNA adiponectin, leptin, interleukin-6 and CD68 expression was reduced, resistin mRNA expression was increased and adiponectin receptor 1 and 2 expression were unchanged as compared to the control group. CONCLUSIONS: Local perturbations in resistin, adiponectin and interleukin-6 mRNA expression in subcutaneous adipose tissue are not reflected by its circulating levels. These changes could be involved in some local metabolic disturbances in subcutaneous adipose tissue of anorexia nervosa patients.
- MeSH
- adiponektin genetika krev MeSH
- antigeny diferenciační myelomonocytární genetika MeSH
- C-reaktivní protein analýza MeSH
- CD antigeny genetika MeSH
- dospělí MeSH
- exprese genu MeSH
- financování organizované MeSH
- fyziologická adaptace MeSH
- interleukin-6 genetika MeSH
- inzulin krev MeSH
- krevní glukóza analýza MeSH
- leptinové receptory krev MeSH
- lidé MeSH
- mentální anorexie imunologie metabolismus MeSH
- messenger RNA analýza MeSH
- neparametrická statistika MeSH
- parakrinní signalizace MeSH
- podkožní tuk chemie imunologie metabolismus MeSH
- podvýživa imunologie metabolismus MeSH
- resistin genetika krev MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH