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: Accumulation of adipose tissue macrophages (ATMs) is observed in obesity and may participate in the development of insulin resistance and obesity-related complications. The aim of our study was to investigate the effect of long-term dietary intervention on ATM content in human adipose tissue. DESIGN: We performed a multi-phase longitudinal study. SUBJECTS AND MEASUREMENTS: A total of 27 obese pre-menopausal women (age 39 ± 2 years, body mass index 33.7 ± 0.5 kg m(-2)) underwent a 6-month dietary intervention consisting of two periods: 4 weeks of very low-calorie diet (VLCD) followed by weight stabilization composed of 2 months of low-calorie diet and 3 to 4 months of weight maintenance diet. At baseline and at the end of each dietary period, samples of subcutaneous adipose tissue (SAT) were obtained by needle biopsy and blood samples were drawn. ATMs were determined by flow cytometry using combinations of cell surface markers. Selected cytokine and chemokine plasma levels were measured using enzyme-linked immunosorbent assay. In addition, in a subgroup of 16 subjects, gene expression profiling of macrophage markers in SAT was performed using real-time PCR. RESULTS: Dietary intervention led to a significant decrease in body weight, plasma insulin and C-reactive protein levels. After VLCD, ATM content defined by CD45+/14+/206+ did not change, whereas it decreased at the end of the intervention. This decrease was associated with a downregulation of macrophage marker mRNA levels (CD14, CD163, CD68 and LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1)) and plasma levels of monocyte-chemoattractant protein-1 (MCP-1) and CXCL5 (chemokine (C-X-C motif) ligand 5). During the whole dietary intervention, the proportion of two ATM subpopulations distinguished by the CD16 marker was not changed. CONCLUSION: A 6-month weight-reducing dietary intervention, but not VLCD, promotes a decrease in the number of the whole ATM population with no change in the relative distribution of ATM subsets.
- MeSH
- bílá tuková tkáň patologie MeSH
- C-reaktivní protein genetika MeSH
- chemokin CXCL5 genetika MeSH
- dospělí MeSH
- down regulace MeSH
- hmotnostní úbytek genetika MeSH
- index tělesné hmotnosti MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- longitudinální studie MeSH
- makrofágy patologie MeSH
- obezita dietoterapie genetika patologie MeSH
- průtoková cytometrie MeSH
- redukční dieta MeSH
- stanovení celkové genové exprese MeSH
- tělesná hmotnost MeSH
- vezikulární transportní proteiny genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Type 2 diabetes and obesity are associated with an enhanced release of a number of adipocytokines. Hyperinsulinemia, frequently present in type 2 diabetes and obesity, might be one of the drivers of the enhanced production of adipocytokines. The aim of this study was to investigate the interstitial levels of cytokines in subcutaneous adipose tissue (SCAT) in response to hyperinsulinemia and the effect of weight-reducing hypocaloric diet on this regulation in obese subjects. Thirteen obese premenopausal women participated in the study. Concentrations of seven cytokines were measured in plasma and in AT interstitial fluid collected by microdialysis during a euglycemic-hyperinsulinemic clamp and during control infusion of physiological saline. A subgroup of six women underwent a 4-wk very-low-calorie diet (VLCD). Microdialysis during the clamp was performed before and at the end of VLCD. Hyperinsulinemia induced an increase of monocyte chemoatractant protein (MCP-1) and IL-6 SCAT interstitial and plasma levels and elevated IL-8 levels in SCAT. The relative changes of IL-6 levels in the dialysate correlated with changes of IL-8 and MCP-1. The interstitial and plasma levels of IL-1β, IL-10, TNFα, and plasminogen activator inhibitor (PAI-1) remained unchanged in response to hyperinsulinemia. VLCD resulted in enhancement of the hyperinsulinemia-induced augmentation of MCP-1, IL-6, and IL-8 interstitial levels. In conclusion, hyperinsulinemia upregulates the interstitial levels of MCP-1, IL-6, and IL-8 in SCAT in obese women, whereas it does not affect IL-1β, IL-10, TNFα, and PAI-1 levels. Hypocaloric diet associated with weight reduction enhances the hyperinsulinemia-induced upregulation of MCP-1, IL-6, and IL-8 in SCAT.
- MeSH
- chemokin CCL2 biosyntéza MeSH
- chemokiny metabolismus MeSH
- cytokiny metabolismus MeSH
- dospělí MeSH
- glykemický clamp MeSH
- homeostáza fyziologie MeSH
- hyperinzulinismus metabolismus MeSH
- interleukin-6 biosyntéza MeSH
- interleukin-8 metabolismus MeSH
- inzulinová rezistence fyziologie MeSH
- kalorická restrikce MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrodialýza MeSH
- obezita metabolismus MeSH
- podkožní tuk metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Východisko. Asociace obezity s metabolickými i kardiovaskulárními chorobami je závislá na rozložení tukové tkáně. Role intraabdominálně uložené, tj. viscerální, tukové tkáně v patogenezi inzulínové rezistence není stále zřejmá. Cílem této práce bylo sledovat vztah mezi inzulínovou rezistencí a podílem viscerální a podkožní tukové tkáně na souboru žen s širokým rozmezím tělesné hmotnosti. Metody a výsledky. Vyšetřeno bylo 62 žen (věku 21–66 let), z nichž 32 bylo neobézních a 30 obézních (BMI > 30 kg/m2). U účastníků studie bylo hodnoceno množství viscerálního a podkožního tuku pomocí počítačové tomografie, možství celkového tělesného tuku bioimpedancí a stupeň inzulínové senzitivity byl hodnocen spotřebou glukosy (M) během euglykemického hyperinzulínního klempu. Obézní ženy měly nižší inzulínovou senzitivitu ve srovnání s neobézními (5,88 ± 2,17 vs. 3,32 ± 1,44 mg/min/kg, p < 0,001) a vyšší absolutní množství viscerálního tuku. Relativní podíl viscerálního tuku (vztaženého k tuku celkovému nebo podkožnímu) nebyl však u obou skupin rozdílný. V celém souboru stupeň inzulínové senzitivity koreloval s absolutním množstvím celkového a viscerálního tuku, nebyla však nalezena korelace s relativním podílem viscerálního tuku. Závěry. Výsledky na tomto souboru nasvědčují tomu, že pro predikci stupně inzulínové rezistence daného jedince je důležitější absolutní množství přítomné tukové tkáně jak celkové, tak viscerální než relativní zastoupení viscerálního tuku.
Background. Association of obesity with metabolic and cardiovascular complications depends on the adipose tissue distribution. The role of intraabdominal, i.e. visceral, adipose tissue in pathogenesis of insulin resistance is still not elucidated. The aim of this study was to investigate the relation between insulin resistance and contribution of visceral and subcutaneous fat in a group of women with a wide range of body weight. Methods and Results. 62 women (age 21–66 years) among which 32 were non-obese and 30 obese (BMI > 30 kg/m2) were examined. The amount of visceral and subcutaneous fat was evaluated using computerized tomography, total body fat evaluated using bioimpedance, and the degree of insulin resistance was evaluated using glucose disposal (M) during euglycemic hyperinsulinemic clamp. Obese women had lower insulin sensitivity than non-obese (5.88 ± 2.17 vs 3.32 ± 1.44 mg/min/kg, p < 0.001) and higher absolute amount of visceral fat. However, the relative amount of visceral fat (related to total body fat or subcutaneous fat) was not different between the two groups. In the entire study group, the magnitude of insulin sensitivity did correlate with absolute amount of total and visceral fat, but no correlation with relative amount of visceral fat was found. Conclusions. The results suggest that the absolute amount of fat, either total or visceral, is a stronger predictor of the degree of insulin resistance than the relative contribution of visceral fat.
- MeSH
- distribuce tělesného tuku MeSH
- financování organizované MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- nitrobřišní tuk patofyziologie MeSH
- obezita komplikace patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Retinol binding protein 4 (RBP4) is a novel adipokine which might be involved in the development of insulin resistance. The aim of the study was to investigate the expression of RBP4 mRNA in subcutaneous and visceral fat depots and the relationship between RBP4 plasma and mRNA levels relative to indices of adiposity and insulin resistance. In 59 Caucasian women (BMI 20 to 49 kg/m2) paired samples of subcutaneous and visceral fat were obtained for RBP4, leptin and GLUT 4 mRNA analysis using reverse transcription-quantitative PCR. Euglycemic hyperinsulinemic clamp and computed tomography scans were performed. RBP4 mRNA levels as well as GLUT 4 mRNA and leptin mRNA levels were lower (P<0.001, P<0.01 and P<0.001, respectively) in visceral compared to subcutaneous fat. No differences were found in RBP4 mRNA expression in the two fat depots or in RBP4 plasma levels between subgroups of non-obese subjects (n=26), obese subjects without metabolic syndrome (n=17) and with metabolic syndrome (n=16). No correlations between RBP4 mRNA or plasma levels relative to adiposity, glucose disposal rate and GLUT 4 mRNA expression in adipose tissue were found. There was a weak positive correlation between plasma RBP4 and plasma triglycerides (r = 0.30, p<0.05) and between plasma RBP4 and blood glucose (r = 0.26, p<0.05). Regardless of the state of adiposity or insulin resistance, RBP4 expression in humans was lower in visceral than in subcutaneous fat. We found no direct relationship between either RBP4 mRNA or its plasma levels and the adiposity or insulin resistance.
- Klíčová slova
- Obesity, Insulin resistance, Visceral and subcutaneous adipose tissue, Retinol-binding protein 4,
- MeSH
- adipozita MeSH
- dospělí MeSH
- financování organizované MeSH
- inzulin krev MeSH
- inzulinová rezistence MeSH
- krevní glukóza analýza MeSH
- leptin analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA analýza MeSH
- metabolický syndrom metabolismus patofyziologie radiografie MeSH
- mladý dospělý MeSH
- nitrobřišní tuk chemie patologie radiografie MeSH
- obezita metabolismus patofyziologie radiografie MeSH
- plazmatické proteiny vázající retinol analýza genetika MeSH
- počítačová rentgenová tomografie MeSH
- podkožní tuk chemie patofyziologie radiografie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- přenašeč glukosy typ 4 analýza MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Background: A novel adipokine, visfatin, was found to be related to adiposity in humans and regulated by a number of hormonal signals. The aim of this study was to investigate the relationships of visfatin expression in adipose tissue with potential regulatory factors such as insulin, testosterone and tumor necrosis factor-alpha (TNF-alpha) and to elucidate the effect of a diet induced weight reduction on adipose tissue mRNA expression and plasma levels of visfatin. MATERIALS AND METHODS: Biopsies of subcutaneous abdominal adipose tissue (SCAAT) and plasma samples were obtained at the beginning of the study from 47 pre-menopausal women (age 38.7 +/- 1.7 years, body mass index (BMI) 27.9 +/- 1.4 kg m(-2)), consisting of 15 lean, 16 overweight and 16 obese subjects. The subgroup of 32 overweight/obese women (age 42.1 +/- 1.9 years, BMI 31.2 +/- 0.9 kg m(-2)) underwent a 12 week hypocaloric weight reducing diet and samples were obtained at the end of the diet. Biopsy samples were analysed for visfatin and TNF-alpha mRNA levels and plasma was analysed for relevant metabolites and hormones. RESULTS: In the group of 47 subjects visfatin mRNA expression in SCAAT was negatively correlated with plasma free testosterone (r = -0. 363, P < 0.05) and BMI (r = -0.558, P < 0.01) and positively associated with adipose tissue TNF-alpha mRNA expression (r = 0.688, P < 0.01). The diet resulted in the reduction of body weight and in the decrease of plasma insulin, free testosterone and TNF-alpha levels. In the group of overweight/obese subjects visfatin mRNA in SCAAT increased after the diet and the diet induced increase was positively correlated with the magnitude of body weight loss. CONCLUSION: Visfatin mRNA expression in SCAAT is associated with TNF-alpha expression, plasma free testosterone and BMI in pre-menopausal women. A weight reducing hypocaloric diet results in the increase of visfatin mRNA in SCAAT.
- MeSH
- distribuce tělesného tuku MeSH
- dospělí MeSH
- financování organizované MeSH
- hmotnostní úbytek fyziologie MeSH
- hormony krev metabolismus MeSH
- index tělesné hmotnosti MeSH
- lidé středního věku MeSH
- lidé MeSH
- nikotinamidfosforibosyltransferasa krev metabolismus MeSH
- podkožní tuk metabolismus MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.
- MeSH
- alfa-2-adrenergní receptory metabolismus MeSH
- dietní tuky MeSH
- dospělí MeSH
- fentolamin farmakologie MeSH
- financování organizované MeSH
- inzulin metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipolýza MeSH
- mastné kyseliny metabolismus MeSH
- mikrodialýza MeSH
- obezita MeSH
- potraviny MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
