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
The role of PPARs in the regulation of human adipose tissue secretome has received little attention despite its potential importance in the therapeutic actions of PPAR agonists. Here, we have investigated the effect of selective PPARgamma, PPARalpha, and PPARbeta/delta agonists on the production of adipokines by human subcutaneous adipose tissue. Antibody arrays were used to measure secreted factors in media from cultured adipose tissue explants. Sixteen proteins were produced in significant amounts. Activation of PPARs regulated the production of five proteins. Treatments with the three PPAR agonists decreased the secretion of leptin and interleukin-6. PPARalpha and beta/delta agonists markedly enhanced hepatocyte growth factor secretion whereas PPARbeta/delta down-regulated angiogenin and up-regulated TIMP-1 release. Hepatocyte growth factor, interleukin-6, and TIMP-1 are chiefly expressed in cells from the stromal vascular fraction whereas angiogenin is expressed in both adipocytes and cells from the stromal vascular fraction. Our data show that PPAR agonists modulate secretion of bioactive molecules from the different cell types composing human adipose tissue.
- MeSH
- cytokiny metabolismus MeSH
- endoteliální buňky metabolismus MeSH
- financování organizované MeSH
- hepatocytární růstový faktor metabolismus MeSH
- interleukin-6 sekrece MeSH
- leptin sekrece MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- obezita MeSH
- podkožní tuk metabolismus MeSH
- proteomika metody MeSH
- receptory aktivované proliferátory peroxizomů agonisté MeSH
- regulace genové exprese MeSH
- stanovení celkové genové exprese MeSH
- tukové buňky metabolismus MeSH
- Check Tag
- lidé MeSH
CONTEXT: Obesity is characterized by a low-grade inflammatory state, which could play a role in insulin resistance. Dynamic strength training improves insulin sensitivity. OBJECTIVE: The objective of this study was to investigate, in obese subjects, whether the insulin sensitizing effect of dynamic strength training is associated with changes in plasma levels and gene expression of adipokines potentially involved in the development of insulin resistance. DESIGN: Twelve obese male subjects were investigated before and at the end of 3 months of dynamic strength training. Insulin sensitivity was evaluated using euglycemic-hyperinsulinemic clamp. Blood samples and needle biopsy samples of sc abdominal adipose tissue were obtained. The plasma levels and adipose tissue mRNA levels of adiponectin, leptin, IL-1beta, IL-6, and TNF-alpha were determined. RESULTS: The training induced an increase in the whole-body glucose disposal rate by 24% (P = 0.04). The body weight was not altered during the training. Plasma levels of leptin decreased during the training (16.6 +/- 6.3 vs. 13.1 +/- 5.7 ng/ml) by 21% (P < 0.02), whereas no change in plasma levels of other adipokines and C-reactive protein was observed. Gene expression of the investigated adipokines was not changed in sc adipose tissue during the training. CONCLUSIONS: In obese subjects, the dynamic strength training resulted in an improvement of whole-body insulin sensitivity. The increase in insulin sensitivity was not associated with training-induced modifications of plasma levels or adipose tissue gene expression of adipokines supposedly involved in the development of insulin resistance.
- MeSH
- adiponektin krev metabolismus MeSH
- cvičení * fyziologie MeSH
- cytokiny * krev metabolismus MeSH
- exprese genu MeSH
- interleukin-1beta krev metabolismus MeSH
- interleukin-6 krev metabolismus MeSH
- inzulinová rezistence * fyziologie MeSH
- leptin krev metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita krev metabolismus MeSH
- podkožní tuk * metabolismus MeSH
- svalová síla fyziologie MeSH
- TNF-alfa krev metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
