"NR8066" Dotaz Zobrazit nápovědu
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
27 l., nestr. příl. : tab. ; 30 cm
The aim of the project is to bring a contribution for understanding the role of visceral adipose tissue to pathogenesis of metabolic syndrome. Molecular genetic characteristics of visceral and subcutaneous adipose tissue will be investigated Attention will be paid to the genes supposed to play a role in pathogenesis of insulin resistence and metabolic syndrome: 1. genes involved in regulation of lipolysis and non-esterified fatty acids release 2. genes encoding synthesis of cytokines The gene expressionwill be investigated in women with signs of metabolic syndrome (n=15) and in a control group (n=15). The samples of adipose tissue will be obtained during diagnostic laparoscopy indicated to the subjects for gynecological reasons Phenotypic characteristics of subjects will include hormonal and metabolic laboratory indices, indices of insulin resistence, body composition, energy metabolism. Levels of mRNA will be measured using real-time PCR and microarray methods
Cílem projektu je přispět k objasnění role viscerální tukové tkáně v etiopatogenesi metabolického syndromu. Budou sledovány molekulárně genetické charakteristiky viscerální a podkožní tukové tkáně. Sledovány budou exprese genů, u nichž je předpokládána role v patogenesi insulinové resistence: 1. geny regulující lipolysu v tukové tkáni a mobilisaci neesterifikovaných mastných kyselin 2. geny kodující syntesu cytokinů v tukové tkáni. Sledovanými soubory budou ženy s projevy metabolického syndromu (n=15) akontrolní skupina (n=15). Vzorky tukové tkáně budou odebrány během diagnostické laparoskopie doporučené u těchto žen z gynekologické indikace nesouvisející¨s předmětem této studie. Fenotypická charakteritika souboru bude obsahovat měření hormonálně- metabolických charakteristik, indexů insulinové resistence, složení těla, energetického metabolismu. Hladiny RNA budou stanoveny metodami real time PCR a microarrays.
- MeSH
- cytokiny biosyntéza MeSH
- exprese genu genetika MeSH
- gynekologická onemocnění genetika metabolismus MeSH
- inzulinová rezistence MeSH
- laparoskopie MeSH
- lipolýza imunologie MeSH
- metabolický syndrom etiologie genetika patofyziologie MeSH
- regulace genové exprese MeSH
- tuková tkáň MeSH
- Konspekt
- Fyziologie člověka a srovnávací fyziologie
- NLK Obory
- vnitřní lékařství
- endokrinologie
- biologie
- gynekologie a porodnictví
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
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
Thyroid dysfunction is associated with several abnormalities in intermediary metabolism, including impairment of lipolytic response to catecholamines in subcutaneous abdominal adipose tissue (SCAAT). Atrial natriuretic peptide (ANP) is a powerful lipolytic peptide; however, the role of ANP-mediated lipolysis in thyroid disease has not been elucidated. The aim of this study was to investigate the role of thyroid hormones in the regulation of ANP-induced lipolysis as well as in the gene expression of hormone-sensitive lipase, phosphodiesterase 3B (PDE3B), uncoupling protein-2 (UCP2), natriuretic peptide receptor type A, and beta(2)-adrenergic receptor in SCAAT of hyperthyroid and hypothyroid patients. Gene expression in SCAAT was studied in 13 hypothyroid and 11 hyperthyroid age-matched women before and 2-4 mo after the normalization of their thyroid status. A microdialysis study was performed on a subset of nine hyperthyroid and 10 hypothyroid subjects. ANP- and isoprenaline-induced lipolyses were higher in hyperthyroid subjects, with no differences between the groups following treatment. Hormone-sensitive lipase gene expression was higher in hyperthyroid compared with hypothyroid subjects before treatment, whereas no difference was observed following treatment. No differences in gene expression of other genes were observed between the two groups. Following treatment, the gene expression of UCP2 decreased in hyperthyroid, whereas the expression of PDE3B decreased in hypothyroid subjects. We conclude that thyroid hormones regulate ANP- and isoprenaline-mediated lipolysis in human SCAAT in vivo. Increased lipolytic subcutaneous adipose tissue response in hyperthyroid patients may involve postreceptor signaling mechanisms.
- MeSH
- atriální natriuretický faktor MeSH
- dospělí MeSH
- energetický metabolismus MeSH
- financování organizované MeSH
- hypertyreóza MeSH
- hypotyreóza MeSH
- isoprenalin MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipolýza MeSH
- podkožní břišní tuk MeSH
- regionální krevní průtok MeSH
- regulace genové exprese MeSH
- senioři MeSH
- tělesná hmotnost MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinické zkoušky kontrolované 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
- MeSH
- finanční podpora výzkumu jako téma MeSH
- Publikační typ
- abstrakty MeSH
AIMS/HYPOTHESIS: The aim of this study was to investigate whether dynamic strength training modifies the control of lipolysis, with particular attention paid to the involvement of the antilipolytic adrenergic alpha 2A receptor (ADRA2A) pathway. METHODS: Twelve obese men (age: 47.4+/-2.8 years; BMI: 32.7+/-0.9) were investigated during a 210-min euglycaemic-hyperinsulinaemic clamp conducted before and after 3 months of dynamic strength training. Before and during the third hour of the clamp, the lipolytic effect of a perfusion of isoproterenol or adrenaline (epinephrine) alone or associated with the ADRA2A antagonist phentolamine was evaluated using the microdialysis method of measuring extracellular glycerol concentration (EGC) in subcutaneous abdominal adipose tissue (SCAAT). In addition, biopsies of SCAAT were carried out before and after training to determine mRNA levels RESULTS: The training increased insulin sensitivity in adipose tissue. The decrease of EGC was more pronounced during the clamp conducted after the training period than during the clamp done in pre-training conditions. Before and after the training, catecholamines induced an increase in EGC, the increase being lower during the clamp on each occasion. The isoproterenol-induced increase in EGC was higher after the training. Adrenaline-induced lipolysis was potentiated by phentolamine after but not before the training. There were no training-induced changes in mRNA levels of key genes of the lipolytic pathway in SCAAT. CONCLUSIONS/INTERPRETATION: In obese subjects, dynamic strength training improves whole-body and adipose tissue insulin responsiveness. It increases responsiveness to the adrenergic beta receptor stimulation of lipolysis and to the antilipolytic action of catecholamines mediated by ADRA2As.
- MeSH
- adrenalin fyziologie MeSH
- alfa-2-adrenergní receptory - antagonisté MeSH
- alfa-2-adrenergní receptory genetika metabolismus MeSH
- antagonisté beta-2-adrenergních receptorů MeSH
- beta-2-adrenergní receptory genetika metabolismus MeSH
- cyklické nukleotidfosfodiesterasy, typ 3 MeSH
- dospělí MeSH
- fentolamin farmakologie MeSH
- financování organizované MeSH
- glycerol analýza chemie MeSH
- glykemický clamp MeSH
- inzulin fyziologie MeSH
- inzulinová rezistence fyziologie MeSH
- isoprenalin farmakologie MeSH
- kyseliny mastné neesterifikované krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipolýza MeSH
- messenger RNA analýza MeSH
- metabolismus lipidů MeSH
- obezita metabolismus patofyziologie MeSH
- podkožní břišní tuk chemie metabolismus MeSH
- sterolesterasa fyziologie genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- klinické zkoušky MeSH