Objective: Metformin was shown to exert an antilipolytic action in adipose tissue (AT) that might mediate beneficial effects on lipid metabolism in diabetic patients. However, during exercise, the inhibition of induced lipolysis in AT would limit the energy substrate supply for working muscle. Thus, the aim of this study was to investigate whether metformin exerts inhibitory effect on exercise-induced lipolysis in subcutaneous adipose tissue (SCAT) (Moro et al., 2007) in humans. Approach: Ten healthy lean men underwent two exercise sessions consisting of 60 min of cycling on bicycle ergometer combined with (a) orally administered metformin and (b) metformin locally administered into SCAT. Microdialysis was used to assess lipolysis in situ in SCAT. Glycerol, metformin and lactate were measured in dialysate and plasma by enzyme colorimetric kits and capillary electrophoresis. Results: Metformin levels increased continuously in plasma during 3 h after oral administration, and peaked after 3.5 h (peak concentration 4 μg/ml). Metformin was detected in dialysate outflowing from SCAT and showed a similar time-course as that in plasma with the peak concentration of 1.3 μg/ml. The lipolytic rate in SCAT (assessed as glycerol release) increased in response to exercise (4.3 ± 0.5-fold vs. basal; p = 0.002) and was not suppressed either by local or oral metformin administration. The lactate levels increased in plasma and in dialysate from SCAT after 30-60 min of exercise (3.6-fold vs. basal; p = 0.015; 2.75-fold vs. basal; p = 0.002, respectively). No effect of metformin on lactate levels in SCAT dialysate or in plasma during exercise was observed. Conclusion: Metformin did not reduce the exercise-induced lipolysis in SCAT. This suggests that metformin administration does not interfere with the lipid mobilization and energy substrate provision during physical activity.

• Klíčová slova
• exercise, human adipose tissue, lactate, lipolysis, metformin, microdialysis,
• Publikační typ
• časopisecké články 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 farmakologie   MeSH
• agonisté beta-2-adrenergních receptorů MeSH
• alfa-2-adrenergní receptory - agonisté MeSH
• alfa-2-adrenergní receptory - antagonisté MeSH
• alfa-2-adrenergní receptory genetika   metabolismus   MeSH
• beta-2-adrenergní receptory genetika   metabolismus   MeSH
• cAMP-fosfodiesterasy genetika   fyziologie   MeSH
• cvičení fyziologie   MeSH
• cyklické nukleotidfosfodiesterasy, typ 3 MeSH
• dospělí MeSH
• fentolamin farmakologie   MeSH
• glycerol analýza   krev   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 genetika   fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adrenalin MeSH
• agonisté beta-2-adrenergních receptorů MeSH
• alfa-2-adrenergní receptory - agonisté MeSH
• alfa-2-adrenergní receptory - antagonisté MeSH
• alfa-2-adrenergní receptory MeSH
• beta-2-adrenergní receptory MeSH
• cAMP-fosfodiesterasy MeSH
• cyklické nukleotidfosfodiesterasy, typ 3 MeSH
• fentolamin MeSH
• glycerol MeSH
• inzulin MeSH
• isoprenalin MeSH
• kyseliny mastné neesterifikované MeSH
• messenger RNA MeSH
• sterolesterasa MeSH