Nejvíce citovaný článek - PubMed ID 20531347
Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women
Residential macrophages in adipose tissue play a pivotal role in the development of inflammation not only within this tissue, but also affect the proinflammatory status of the whole body. Data on human adipose tissue inflammation and the role of macrophages are rather scarce. We previously documented that the proportion of proinflammatory macrophages in human adipose tissue correlates closely with non-HDL cholesterol concentrations. We hypothesized that this is due to the identical influence of diet on both parameters and decided to analyze the fatty acid spectrum in cell membrane phospholipids of the same individuals as a parameter of the diet consumed. Proinflammatory and anti-inflammatory macrophages were isolated from human adipose tissue (n = 43) and determined by flow cytometry as CD14+CD16+CD36high and CD14+CD16-CD163+, respectively. The spectrum of fatty acids in phospholipids in the cell membranes of specimens of the same adipose tissue was analyzed, and the proportion of proinflammatory macrophage increased with the proportions of palmitic and palmitoleic acids. Contrariwise, these macrophages decreased with increasing alpha-linolenic acid, total n-3 fatty acids, n-3/n-6 ratio, and eicosatetraenoic acid. A mirror picture was documented for the proportion of anti-inflammatory macrophages. The dietary score, obtained using a food frequency questionnaire, documented a positive relation to proinflammatory macrophages in individuals who consumed predominantly vegetable fat and fish, and individuals who consumed diets based on animal fat without fish and nut consumption. he present data support our hypothesis that macrophage polarization in human visceral adipose tissue is related to fatty acid metabolism, cell membrane composition, and diet consumed. It is suggested that fatty acid metabolism might participate also in inflammation and the risk of developing cardiovascular disease.
- Klíčová slova
- inflammation, macrophages, membrane, nutrition, omega-3 fatty acids,
- MeSH
- buněčná membrána chemie MeSH
- dieta MeSH
- dospělí MeSH
- fosfolipidy chemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy fyziologie MeSH
- mastné kyseliny chemie MeSH
- tuková tkáň cytologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfolipidy MeSH
- mastné kyseliny MeSH
BACKGROUND/OBJECTIVES: OxLDL-β2GPI complex has been suggested to have a role in the development of atherosclerosis and other inflammatory diseases. The aim of this study was to investigate the possible association of circulating oxLDL-β2GPI with obesity-induced inflammatory state of adipose tissue and related comorbidities as metabolic syndrome development. SUBJECTS/METHODS: Two cohorts of subjects were examined in the study. Cohort I: 36 women with wide range of body mass index (17-48 kg m-2) and metabolic status (with or without metabolic syndrome (MS); cohort II: 20 obese women undergoing a dietary intervention (DI) consisting of 1-month very-low-calorie diet, and 5 months of weight-stabilization period. Serum levels of oxLDL-β2GPI were measured by enzyme-linked immunosorbent assay. Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp and homeostasis model assessment of insulin resistance. mRNA expression of macrophage markers was determined in both subcutaneous (SAT) and visceral (VAT) adipose tissue in cohort I and in SAT in cohort II. RESULTS: Serum oxLDL-β2GPI levels were increased in obese subjects with MS compared to lean or obese without MS (obese with MS: 26.6±5.0 vs lean: 15.17±1.97, P<0.001; vs obese without MS: 16.36±2.89, P<0.05). Serum oxLDL-β2GPI correlated with MS indices (glucose, high-density lipoprotein, triglyceride and ureic acid) and with mRNA expression of macrophage markers in VAT. Weight-reducing DI decreased serum oxLDL-β2GPI levels together with lipid parameters and the mRNA expression of inflammatory markers in SAT. CONCLUSIONS: OxLDL-β2GPI seems to be an important marker of visceral adipose tissue inflammation and possibly a factor contributing to insulin resistance and metabolic syndrome development in obese patients.
- MeSH
- beta-2-glykoprotein I krev chemie metabolismus MeSH
- biologické markery krev MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny LDL krev chemie metabolismus MeSH
- metabolický syndrom krev patofyziologie MeSH
- multiproteinové komplexy MeSH
- obezita * krev metabolismus patofyziologie MeSH
- tuková tkáň metabolismus patofyziologie MeSH
- zánět krev patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-2-glykoprotein I MeSH
- biologické markery MeSH
- lipoproteiny LDL MeSH
- multiproteinové komplexy MeSH
- oxidized low density lipoprotein MeSH Prohlížeč
Obesity is accompanied by the development of chronic low-grade inflammation in adipose tissue. The presence of chronic inflammatory response along with metabolically harmful factors released by adipose tissue into the circulation is associated with several metabolic complications of obesity such as type 2 diabetes mellitus or accelerated atherosclerosis. The present review is focused on macrophages and lymphocytes and their possible role in low-grade inflammation in fat. Both macrophages and lymphocytes respond to obesity-induced adipocyte hypertrophy by their migration into adipose tissue. After activation and differentiation, they contribute to the development of local inflammatory response and modulation of endocrine function of adipose tissue. Despite intensive research, the exact role of lymphocytes and macrophages within adipose tissue is only partially clarified and various data obtained by different approaches bring ambiguous information with respect to their polarization and cytokine production. Compared to immunocompetent cells, the role of adipocytes in the obesity-related adipose tissue inflammation is often underestimated despite their abundant production of factors with immunomodulatory actions such as cytokines or adipokines such as leptin, adiponektin, and others. In summary, conflicting evidence together with only partial correlation of in vitro findings with true in vivo situation due to great heterogeneity and molecular complexity of tissue environment calls for intensive research in this rapidly evolving and important area.
- Klíčová slova
- Adipocytes, Low-grade inflammation, Lymphocytes, Macrophages, Obesity,
- MeSH
- adipokiny metabolismus MeSH
- biologické markery metabolismus MeSH
- cytokiny metabolismus MeSH
- diabetes mellitus 2. typu etiologie MeSH
- lidé MeSH
- makrofágy imunologie MeSH
- myši MeSH
- obezita imunologie patologie MeSH
- T-lymfocyty pomocné-indukující imunologie MeSH
- tuková tkáň cytologie imunologie patologie MeSH
- zánět imunologie patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- adipokiny MeSH
- biologické markery MeSH
- cytokiny MeSH
The importance of the involvement of adipose tissue macrophage subpopulations in obesity-related disorders is well known from different animal models, but human data are scarcer. Subcutaneous (n=44) and visceral (n=52) adipose tissues of healthy living kidney donors were obtained during living donor nephrectomy. Stromal vascular fractions were isolated and analysed by flow cytometry using CD14, CD16, CD36 and CD163 antibodies. Total macrophage numbers in subcutaneous adipose tissue increased (P=0.02) with body mass index (BMI), with a similar increase seen in the proportion of phagocytic CD14+CD16+CD36high macrophages (P<0.01). On the other hand, there was an inverse correlation between anti-inflammatory CD14+CD16-CD163+ macrophages (P<0.05) and BMI. These correlations disappeared after excluding obese subjects (BMI ⩾30 kg m-2) from the analysis. Interestingly, none of these subpopulations were significantly related to BMI in visceral adipose tissue. Obesity per se is associated with distinct, highly phagocytic macrophage accumulation in human subcutaneous adipose tissue.
- MeSH
- dospělí MeSH
- fagocyty metabolismus MeSH
- index tělesné hmotnosti * MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy metabolismus MeSH
- nitrobřišní tuk metabolismus MeSH
- obezita komplikace metabolismus MeSH
- podkožní tuk metabolismus MeSH
- zánět etiologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND AND AIMS: Macrophages play important roles in adipose tissue inflammation and its consequences. Unfortunately, a detailed description of the macrophage phenotypes in different human adipose tissues is not available. SUBJECTS AND METHODS: Subcutaneous, visceral and perivascular adipose tissues were obtained from 52 living kidney donors during live donor nephrectomy. Stromal vascular fractions were isolated, and the macrophage phenotypes were analyzed by flow cytometry using surface markers (CD14, CD16, CD36, and CD163). RESULTS: In addition to CD16 positivity, pro-inflammatory macrophages also display high scavenger receptor CD36 expression. The great majority of CD16 negative macrophages express the anti-inflammatory CD163 marker. The presence of pro-inflammatory macrophages was almost twice as high in visceral (p < 0.0001) and perivascular (p < 0.0001) adipose tissues than in subcutaneous tissue. This difference was substantially more pronounced in the postmenopausal women subgroup, consequentlly, the total difference was driven by this subgroup. CONCLUSION: We obtained detailed information about M1 and M2 macrophage phenotypes in human adipose tissue. The visceral and perivascular adipose tissues had substantially higher pro-inflammatory characteristics than the subcutaneous tissue. The higher proportion of pro-inflammatory macrophages in the visceral adipose tissue of postmenopausal women might be related to an increased cardiovascular risk.
- Klíčová slova
- Adipose tissue, Inflammation, Macrophages, Menopause,
- MeSH
- dárci tkání MeSH
- fenotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy cytologie MeSH
- nitrobřišní tuk cytologie MeSH
- podkožní tuk cytologie MeSH
- průtoková cytometrie MeSH
- separace buněk MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
BACKGROUND/OBJECTIVES: Hyperglycemia represents one of possible mediators for activation of immune system and may contribute to worsening of inflammatory state associated with obesity. The aim of our study was to investigate the effect of a short-term hyperglycemia (HG) on the phenotype and relative content of immune cells in circulation and subcutaneous abdominal adipose tissue (SAAT) in obese women without metabolic complications. SUBJECTS/METHODS: Three hour HG clamp with infusion of octreotide and control investigations with infusion of octreotide or saline were performed in three groups of obese women (Group1: HG, Group 2: Octreotide, Group 3: Saline, n=10 per group). Before and at the end of the interventions, samples of SAAT and blood were obtained. The relative content of immune cells in blood and SAAT was determined by flow cytometry. Gene expression analysis of immunity-related markers in SAAT was performed by quantitative real-time PCR. RESULTS: In blood, no changes in analysed immune cell population were observed in response to HG. In SAAT, HG induced an increase in the content of CD206 negative monocytes/macrophages (p<0.05) and T lymphocytes (both T helper and T cytotoxic lymphocytes, p<0.01). Further, HG promoted an increase of mRNA levels of immune response markers (CCL2, TLR4, TNFα) and lymphocyte markers (CD3g, CD4, CD8a, TBX21, GATA3, FoxP3) in SAAT (p<0.05 and 0.01). Under both control infusions, none of these changes were observed. CONCLUSIONS: Acute HG significantly increased the content of monocytes and lymphocytes in SAAT of healthy obese women. This result suggests that the short-term HG can modulate an immune status of AT in obese subjects.
- MeSH
- biologické markery metabolismus MeSH
- C-peptid krev MeSH
- dospělí MeSH
- fenotyp MeSH
- hyperglykemie krev chemicky indukované komplikace imunologie MeSH
- inzulin krev MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- makrofágy cytologie účinky léků MeSH
- messenger RNA genetika metabolismus MeSH
- monocyty cytologie účinky léků MeSH
- obezita komplikace MeSH
- oktreotid farmakologie MeSH
- počet buněk MeSH
- podkožní břišní tuk účinky léků imunologie MeSH
- regulace genové exprese účinky léků MeSH
- T-lymfocyty cytologie účinky léků MeSH
- zdraví * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinická studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- C-peptid MeSH
- inzulin MeSH
- krevní glukóza MeSH
- messenger RNA MeSH
- oktreotid MeSH
AIMS/HYPOTHESIS: Our goal was to identify a set of human adipose tissue macrophage (ATM)-specific markers and investigate whether their gene expression in subcutaneous adipose tissue (SAT) as well as in visceral adipose tissue (VAT) is related to obesity and to the occurrence of the metabolic syndrome. METHODS: ATM-specific markers were identified by DNA microarray analysis of adipose tissue cell types isolated from SAT of lean and obese individuals. We then analysed gene expression of these markers by reverse transcription quantitative PCR in paired samples of SAT and VAT from 53 women stratified into four groups (lean, overweight, obese and obese with the metabolic syndrome). Anthropometric measurements, euglycaemic-hyperinsulinaemic clamp, blood analysis and computed tomography scans were performed. RESULTS: A panel of 24 genes was selected as ATM-specific markers based on overexpression in ATM compared with other adipose tissue cell types. In SAT and VAT, gene expression of ATM markers was lowest in lean and highest in the metabolic syndrome group. mRNA levels in the two fat depots were negatively correlated with glucose disposal rate and positively associated with indices of adiposity and the metabolic syndrome. CONCLUSIONS/INTERPRETATION: In humans, expression of ATM-specific genes increases with the degree of adiposity and correlates with markers of insulin resistance and the metabolic syndrome to a similar degree in SAT and in VAT.
- MeSH
- dospělí MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy metabolismus MeSH
- metabolický syndrom metabolismus MeSH
- mladý dospělý MeSH
- nadváha metabolismus MeSH
- nitrobřišní tuk cytologie metabolismus MeSH
- obezita metabolismus MeSH
- podkožní tuk cytologie metabolismus MeSH
- senioři MeSH
- tuková tkáň cytologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH