Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat.

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.

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women.

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.

[Relation between insulin resistance and amount of visceral adipose tissue]. / Vztah inzulíinové rezistence a mnozství 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.

Visfatin expression in subcutaneous adipose tissue of pre-menopausal women: relation to hormones and weight reduction.

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.

Retinol-binding protein 4 expression in visceral and subcutaneous fat in human obesity.

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/m(2)) 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.

Dynamic strength training improves insulin sensitivity without altering plasma levels and gene expression of adipokines in subcutaneous adipose tissue in obese men.

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.

Dynamic strength training improves insulin sensitivity and functional balance between adrenergic alpha 2A and beta pathways in subcutaneous adipose tissue of obese subjects.

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.

[Effect of dynamic strength training on insulin sensitivity in men with insulin resistance]. / Vliv silove-dynamického tréninku na inzulínovou senzitivitu u inzulínorezistentních muzu.

BACKGROUND: Physical activity is generally accepted as a part of the nonpharmacological therapy of the insulin resistance. Endurance training is generally recommended as an appropriate approach. The aim of this study was to assess the effect of three-month dynamic strength training on the insulin sensitivity in middle-aged men with insulin resistance. METHODS AND RESULTS: 10 men (5 obese non diabetics and 5 overweight patients with diabetes mellitus type 2 (age 51.36+/-7.25 years, average weight 110.16+/-13.56 kg and BMI 33.22+/-3.52 kg/m2 underwent a three-month dynamic strength training at the level of 60 to 70 % of their maximum muscle strength (one-repetition maximum 1-RM). Insulin sensitivity was determined using the hyperinsulinic euglycemic clamp before and after the training period. Training promoted to increase the muscle strength (p<0.001). It did not induce changes in body weight, body composition and maximum aerobic capacity. The training induced an increase in insulin sensitivity (glucose disposal M: 3.0 vs 4.0 M - mg/min/kg, p<0,01). CONCLUSIONS: Dynamic strength training improves insulin sensitivity in men with insulin resistance independently on weight loss or increase in aerobic capacity. Our results suggest that the dynamic strength training is an appropriate physical activity for management of the insulin resistance.

Hypocaloric diet reduces exercise-induced alpha 2-adrenergic antilipolytic effect and alpha 2-adrenergic receptor mRNA levels in adipose tissue of obese women.

Previous investigations have shown that alpha 2-adrenoceptor (alpha 2-AR) stimulation blunts lipid mobilization during physiological activation of the sympathetic nervous system promoted by exercise in sc abdominal adipose tissue (SCAAT) in obese men. To investigate the effect of a low calorie diet (LCD) on the alpha 2-adrenergic responsiveness and on the expression of alpha 2-AR and beta 2-adrenoceptor (beta 2-AR) in SCAAT, 11 obese women (weight: 99.1 +/- 4.6 kg; body mass index: 34.3 +/- 1.1 kg/m(2)) received a 12-wk diet providing 500 kcal/d less than their usual diet. The exercise-induced alpha 2-adrenergic antilipolytic effect was investigated in SCAAT before and at the end of LCD. Changes in extracellular glycerol concentration and local blood flow were measured in SCAAT during a 45-min exercise bout (50% of heart rate reserve) using a control microdialysis probe and a probe supplemented with the alpha2-AR antagonist phentolamine. SCAAT biopsies were performed for determination of mRNA levels using RT-competitive PCR. Plasma catecholamine responses to exercise bout were not different before and at the end of LCD. Before LCD, the exercise-induced increase in extracellular glycerol concentration was potentiated by phentolamine supplementation, while this potentiating effect of the alpha-antagonist was not observed at the end of LCD. No changes were observed for beta 2-AR and hormone-sensitive lipase mRNA levels, while alpha 2-AR mRNA level was significantly decreased in adipose tissue during LCD. These findings show that alpha 2-AR-mediated antilipolytic action is reduced by a moderate hypocaloric diet and that down-regulation of alpha 2-AR mRNA levels may participate in the decrease of the alpha 2-adrenergic effect revealed by microdialysis.

Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women.

OBJECTIVE: We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 microg/m(2) min for 60 min). SUBJECTS: Ten obese women from 40.5+/-3.4 y old were selected for this study. Their body weight was 96.4+/-5.7 kg and their BMI was 35.3+/-1.7 kg/m(2). They received a 2.5-2.9 MJ/day formula diet for 28 days. DESIGN: Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis. RESULTS: The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80-100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment. CONCLUSION: The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol- and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects.

[The most common causes of hypoactivity]. / Nejcastejsí príciny hypoaktivity.

UNLABELLED: Although the physical activity (PA) is the important part of therapy of obesity, its level is generally insufficient. The aim of this study was to find out what are the most frequent reasons preventing people from getting PA. Data were obtained in the form of a questionnaire from 504 office clerks. Twenty-five possible reasons, with a five-degree scale of answers (from never to very often) were offered in reply to the question: "How often do the following prevent you from getting exercise?" THE RESULTS: a lack of time, volitional qualities and lack of finance are the most frequent obstacles to getting exercise. It was analysed the influence of BMI on this obstacles. Possible solutions are proposed in conclusion.

In vitro and in vivo impairment of alpha2-adrenergic receptor-dependent antilipolysis by fatty acids in human adipose tissue.

The aim of the present study was to study the influence of fatty acids on the adrenergic control of lipolysis both in vitro and in vivo. Human subcutaneous adipose tissue explants were cultured for 48 h in the presence of 100 microM bromopalmitate (BrPal), and lipolysis was measured in isolated adipocytes. In control conditions, beta-AR-dependent activation of lipolysis by epinephrine was almost undetectable, and could be fully restored by pharmacological blockade of alpha2-AR-dependent antilipolysis. After BrPal treatment, epinephrine became fully lipolytic and was no longer influenced by alpha2-AR-blockade. Radioligand binding analysis revealed that BrPal treatment led to a significant reduction in the coupling of alpha2-AR to G proteins. In parallel, a chronic and significant increase in plasma fatty acids resulting from a 4-day high-fat diet (HFD) was accompanied by an impairment of the amplifying effect of the alpha2-AR antagonist phentolamine on exercise-induced lipolysis (measured in the subcutaneous adipose tissue with the use of a microdialysis probe) normally observed after a low-fat diet. In conclusion, in vitro and in vivo studies showed that fatty acids impair alpha2-AR-dependent antilipolysis.

Lack of alpha(2)-adrenergic antilipolytic effect during exercise in subcutaneous adipose tissue of trained men.

The aim of this study was to investigate the involvement of the antilipolytic alpha(2)-adrenergic receptor pathway in the regulation of lipolysis during exercise in subcutaneous abdominal adipose tissue (SCAAT). Seven trained men and 15 untrained men were studied. With the use of microdialysis, the extracellular glycerol concentration was measured in SCAAT at rest and during 60 min of exercise at 50% of maximal oxygen consumption. One microdialysis probe was perfused with Ringer solution; the other was supplemented with phentolamine (alpha(2)-adrenergic receptor antagonist). No differences in baseline extracellular or plasma glycerol concentrations were found between the two groups. The exercise-induced extracellular and plasma glycerol increase was higher in trained compared with untrained subjects (P < 0.05). Addition of phentolamine to the perfusate enhanced the exercise-induced response of extracellular glycerol in untrained subjects but not in trained subjects. The exercise-induced increase in plasma norepinephrine and epinephrine concentrations and the decrease in plasma insulin were not different in the two groups. These in vivo findings demonstrate higher exercise-induced lipolysis in trained compared with untrained subjects and show that, in trained subjects, the alpha(2)-mediated antilipolytic action is not involved in the regulation of lipolysis in SCAAT during exercise.

[Effect of nutrition on adipose tissue metabolism in humans]. / Vliv výzivy na metabolismus tukové tkáne u cloveka.

Lipolysis in adipose tissue and balance between energy intake and expenditure are involved in the regulation of adipose tissue mass. Several recent findings suggest that alterations in the regulation of lipolysis and/or energy balance might contribute to the development of obesity. Hormone-sensitive lipase and uncoupling proteins play important role in regulation of lipolysis in adipose tissue as well as in the regulation of energy balance of various tissues. Mechanisms of the control of expression of genes coding synthesis of these proteins are poorly known. A brief overview of the present knowledge of the effects of nutritional intervention on the regulation of lipolysis in adipose tissue and on the expression of genes of hormone-sensitive lipase and that of uncoupling proteins is given in this article. Results of the authors' studies on the effect of calorie restriction on gene expression in adipose tissue are presented.

Activation of alpha(2)-adrenergic receptors impairs exercise-induced lipolysis in SCAT of obese subjects.

With the use of the microdialysis method, exercise-induced lipolysis was investigated in subcutaneous adipose tissue (SCAT) in obese subjects and compared with lean ones, and the effect of blockade of alpha(2)-adrenergic receptors (ARs) on lipolysis during exercise was explored. Changes in extracellular glycerol concentrations and blood flow were measured in SCAT in a control microdialysis probe at rest and during 60-min exercise bouts (50% of heart rate reserve) and in a probe supplemented with the alpha(2)-AR antagonist phentolamine. At rest and during exercise, plasma norepinephrine and epinephrine concentrations were not different in obese compared with lean men. In the basal state, plasma and extracellular glycerol concentrations were higher, whereas blood flow was lower in SCAT of obese subjects. During exercise, the increase of plasma glycerol was higher in obese subjects (115 +/- 35 vs. 65 +/- 21 micromol/l). Oppositely, the exercise-induced increase in extracellular glycerol concentrations in SCAT was five- to sixfold lower in obese than in lean subjects (50 +/- 14 vs. 318 +/- 53 micromol/l). The exercise-induced increase in extracellular glycerol concentration was not significantly modified by phentolamine infusion in lean subjects but was strongly enhanced in the obese subjects and reached the concentrations found in lean sujects (297 +/- 46 micromol/l). These findings demonstrate that the physiological stimulation of SCAT adipocyte alpha(2)-ARs during exercice-induced sympathetic nervous system activation contributes to the blunted lipolysis noted in obese men.

Activation of antilipolytic alpha(2)-adrenergic receptors by epinephrine during exercise in human adipose tissue.

The involvement of the antilipolytic alpha(2)-adrenergic pathway and the specific role of epinephrine in the control of lipolysis during exercise in adipose tissue (AT) were investigated in healthy male subjects (age: 24.1 +/- 2.2 yr; body mass index: 23.0 +/- 1.6). An in vitro study carried out on isolated adipocytes showed that the weak lipolytic effect of epinephrine was potentiated after blockade of alpha(2)-adrenergic receptor (AR) by an alpha(2)-AR antagonist and reached that of isoproterenol, a beta-AR agonist. The effect of the nonselective alpha(2)-AR antagonist phentolamine on the response of the extracellular glycerol concentration (EGC) in AT during two successive bouts of aerobic exercise (50% maximum O(2) uptake, 60 min duration) was evaluated using the microdialysis method. The metabolic responses measured in perfused probes with Ringer solution were compared with those obtained in perfused probes with Ringer plus 0.1 mmol/l phentolamine. Plasma norepinephrine level was not different during the two exercise bouts, whereas that of epinephrine was 2.5-fold higher during the second exercise. EGC in AT was twofold higher in the second compared with the first exercise, and the same response pattern was found for plasma glycerol. The exercise-induced increase in EGC was higher in the probe perfused with phentolamine compared with the control probe in both bouts of exercise. However, the potentiating effect of phentolamine on EGC was significant during the second exercise bout but did not reach a significant level during the first. These results suggest that epinephrine is involved in the control of lipid mobilization through activation of antilipolytic alpha(2)-AR in human subcutaneous AT during exercise.

Endurance training increases the beta-adrenergic lipolytic response in subcutaneous adipose tissue in obese subjects.

OBJECTIVE: The aim of this study was to assess, by longitudinal follow-up, the influence of aerobic training on the in vivo lipolytic activity of adipose tissue in obese male subjects. SUBJECTS: Eleven obese non-diabetic males, aged 41.5+/-5.77 (range 27-49 y) with body mass index (BMI) 36.5+/-4.5 kg/m2 (range 29.4-47.1 kg/m2) participated in the study. DESIGN: Subjects took part in a 12-week aerobic training program. Before and after training, microdialysis of abdominal subcutaneous adipose tissue (SCAT) was carried out, using perfusion with graded doses of the beta-adrenergic agonist isoprenaline and a single dose of the phosphodiesterase inhibitor theophylline. In addition, the response of plasma glycerol and free fatty acids (FFAs) to intravenous infusion of graded doses of isoprenaline was tested. RESULTS: The training did not induce significant weight loss and promoted an increase in maximum aerobic capacity (P<0.05). The increase of extracellular glycerol in SCAT in response to isoprenaline perfusion was enhanced after the training (P<0.05), while no change in the response of interstitial glycerol to theophylline action was observed. The training did not elicit a change in the isoprenaline-induced changes of blood flow in adipose tissue. The increases of plasma FFAs and glycerol in response to intravenous isoprenaline infusion, were significantly enhanced after training. CONCLUSION: The present study shows that aerobic training induced an increase in the response of plasma and subcutaneous adipose tissue concentration of glycerol to beta-adrenergic stimulation. The effect of an agent acting at the post-receptor level (theophylline) in SCAT was not modified by training.

Endurance training changes in lipolytic responsiveness of obese adipose tissue.

The aim of this study was to investigate the effect of aerobic exercise training on the lipolytic response of adipose tissue in obese subjects. Thirteen men (body mass index = 36.9 +/- 1.3 kg/m2) were submitted to aerobic physical training on a cycloergometer (30-45 min, 4 days a wk) for 3 mo. Adipocyte sensitivity to the action of catecholamines and insulin was studied in vitro before and after training. Training induced a decrease in the percentage of fat mass (P < 0.05) without changing the body weight. Basal lipolysis and hormone-sensitive lipase activity were significantly decreased after training (P < 0.05). The lipolytic effects of epinephrine, isoprenaline (beta-adrenoceptor agonist), and dobutamine (beta1-adrenoceptor agonist) were significantly increased (P < 0.05) but not those of procaterol (beta2-adrenoceptor agonist). The antilipolytic effects of alpha2-adrenoceptor and insulin were significantly decreased (P < 0.05). Lipolysis stimulation by agents acting at the postreceptor level was unchanged after training. In conclusion, aerobic physical training in obese male subjects modifies adipose tissue lipolysis through an enhancement of beta-adrenergic response and a concomitant blunting of adipocyte antilipolytic activity.

Microdialysis in investigation of adipose tissue metabolism.

Microdialysis--a technique available since more than two decades--has been recently applied in investigation of metabolism of adipose tissue in humans. The technique enables a continuous sampling of metabolites and other small molecules in the extracellular space of subcutaneous adipose tissue and it enables a local exposure of adipose tissue to metabolically active agents. The method has been used to determine the interstitial concentrations of metabolites (glycerol, glucose, lactate etc.) in adipose tissue and to investigate the regulation of lipolysis and of carbohydrate metabolism in situ in subcutaneous adipose tissue. The method has been widely used in clinical research of adipose tissue and it is supposed to be used for continuous monitoring of metabolites in clinical practice.