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2-Adrenergic Antilipolytic Effect and 2-Adrenergic Receptor mRNA Levels in Adipose Tissue of Obese Women
Department of Sport Medicine and Obesity Unit (V.S., J.H., H.S.) , Charles University, Prague, 10000 Czech Republic; INSERM Unit 317, Laboratory of Medical and Clinical Pharmacology (N.V., C.L., D.L., M.L., M.B.), Faculty of Medicine, Toulouse 31073, France; and Department of the Adaptation to Exercise (F.M.-L.), Purpan Hospital, Toulouse 31073, France
Address all correspondence and requests for reprints to: Dr. Michel Berlan, INSERM U 317, Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, 37 Allées Jules Guesde, 31073 Toulouse cedex, France. E-mail: . berlan{at}cict.fr
Abstract
Previous investigations have shown that 
2-adrenoceptor (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 2-adrenergic responsiveness and on the expression of 2-AR and ß2-adrenoceptor (ß2-AR) in SCAAT, 11 obese women (weight: 99.1 ± 4.6 kg; body mass index: 34.3 ± 1.1 kg/m2) received a 12-wk diet providing 500 kcal/d less than their usual diet. The exercise-induced 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 2-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 -antagonist was not observed at the end of LCD. No changes were observed for ß2-AR and hormone-sensitive lipase mRNA levels, while 2-AR mRNA level was significantly decreased in adipose tissue during LCD. These findings show that 2-AR-mediated antilipolytic action is reduced by a moderate hypocalorie diet and that down-regulation of 2-AR mRNA levels may participate in the decrease of the 2-adrenergic effect revealed by microdialysis.
HUMAN ADIPOCYTES EXPRESS significant levels of ß1-, ß2-, and 2-adrenergic receptors (ARs), which couple positively (ß1- and ß2-ARs) and negatively (2-AR) to adenylyl cyclase (1). The relative contributions of ß- and 2-ARs to the fine tuning of the lipolytic response has been demonstrated by functional in vitro assays in isolated human fat cells. Moreover, binding studies with selective ligands have been used to determine the affinity patterns of the various fat cell AR subtypes for catecholamines (2, 3). In vitro studies in isolated human fat cells have shown that the activation of 2-ARs by epinephrine and norepinephrine impairs the ß-adrenergic component of catecholamine-induced lipolysis. In human fat cells, where 2-AR outnumber ß-AR, the preferential recruitment of the 2-AR at the lowest catecholamine concentrations inhibits lipolysis (4). In both men and women, the 2-adrenergic antilipolytic effect is stronger in the adipocytes from sc adipose tissue (SCAAT) than in omental adipocytes (1). The antilipolytic action of catecholamines, particularly that of epinephrine—which exhibits a high affinity for the 2-AR (4)—has been shown to be higher in isolated sc adipocytes from obese subjects (5). In the search for relevant physiological protocols, exercise was used to activate the sympathetic nervous system (SNS). Exercise-increased SNS activity is responsible for exercise-promoted lipid mobilization in normal subjects. Catecholamines are of major importance for the regulation of lipid mobilization in human adipose tissue during exercise (6, 7, 8) and for the increase of nonesterified fatty acid (NEFA) supply to the working muscle (7, 9, 10). Microdialysis is a method particularly suitable to study the in vivo lipolytic responses of adipose tissue to pharmacological or endogenous stimulation (11, 12, 13, 14, 15). It was demonstrated that 2-ARs are involved in the regulation of lipolysis during an acute bout of exercise (16). Taking into account that the adipocytes of SCAAT from obese men express the highest known 2-AR-mediated antilipolytic component in vitro (5), we also demonstrated that exercise-induced lipolysis in SCAAT is impaired in obese men and that the physiological stimulation of adipocyte 2-ARs during exercise contributes to this impairment. The blunting of lipid mobilization was suppressed through local administration of an 2-AR antagonist (17).
The aim of the present study was to assess the effect of a moderate hypocalorie diet on the 2-adrenergic pathway in SCAAT in obese women. Using in situ microdialysis, the changes in lipolysis and local blood flow were studied in SCAAT during exercise (45 min, 50% of their heart rate reserve), and the effect of the blockade of 2-ARs on these changes was explored. Quantification of mRNA levels in SCAAT was performed by RT-competitive PCR. The findings show that 2-ARs are involved in the regulation of exercise-induced lipolysis in SCAAT in obese women and that the physiological stimulation of adipocyte 2-ARs during exercise—and the resulting antilipolytic effect—is reduced during the hypocalorie diet. Moreover, hypocalorie diet reduces 2-AR mRNA levels without any change in ß2-AR or hormone-sensitive lipase (HSL) mRNA levels.
Subjects and Methods
Patients
Eleven obese women (36.2 ± 6.1 yr) participated in the study. Mean body weight and body mass index were 99.1 ± 4.6 kg (range: 82.3–126.2 kg) and 34.3 ± 1.1 kg/m2, respectively. All subjects were drug free, and their weight had remained stable for at least 3 months before the beginning of the study. They all gave written informed consent before the experiments began. The studies were performed according to the Declaration of Helsinki and approved by the Ethical Committee of the Third Faculty of Medicine (Prague, Czech Republic).
Experimental protocol
The subjects were investigated at 0800 h after an overnight fast, in a semirecumbent position, before and during the last 2 d of 12 wk of hypocalorie diet [low calorie diet (LCD)]. Four to 5 d before the investigation, the maximum exercise test on a bicycle ergometer (Ergoline 800) was performed in each subject to determine the peak oxygen consumption (VO2max) using indirect calorimetry (Vmax, Sensor Medics, Yorba Linda, CA). During the first of the investigation days and at the end of the LCD, a needle biopsy of abdominal SCAAT (200–300 mg) was performed in the left part of the periumbilical region. RNA was extracted using the QIAGEN RNeasy kit (Courtaboeuf, France) and immediately frozen at -80 C until analysis. The following day, two microdialysis probes (Carnegie Medicin, Stockholm, Sweden) of 20 x 0.5 mm and 20,000-MW cut-off were inserted percutaneously after epidermal anesthesia (200 µl of 1% lidocaine, Roger-Bellon, Neuilly-sur-Seine, France) into the abdominal SCAAT at a distance of 10 cm to the right of the umbilicus. Two probes, separated by at least 10 cm, were connected to a microinjection pump (Harvard apparatus, Les Ulis, France). One probe was perfused with Ringer’s solution (139 mmol/liter sodium, 2.7 mmol/liter potassium, 0.9 mmol/liter calcium, 140.5 mmol/liter chloride) and the second with Ringer plus 0.1 mmol/liter phentolamine (-AR antagonist). This nonselective 1-/2-antagonist, having an efficient 2-AR antagonist action in human fat cells in vitro, was the only agent allowed by the Ethical Committee for use in microdialysis assays in humans. The perfusate solutions were supplemented with ethanol (1.7 g/liter). Ethanol was added to the perfusate to estimate changes occurring in the local blood flow in SCAAT, as previously described (18, 19). After a 30-min equilibration period, a 30-min fraction of dialysate was then collected at a flow rate of 0.5 µl/min. Then, the perfusion was set at 2.5 µl/min for the remaining experimental period. A calibration procedure using various perfusion rates for determination of interstitial glycerol concentration in AT has already been reported by our group (12, 10, 17). A simplified but relevant and less time-consuming method was selected in this study. The estimated extracellular glycerol and lactate concentrations were calculated by plotting (after log-transformation) the concentration of glycerol and lactate in the dialysate measured at 0.5 and 2.5 µl/min against the perfusion rates. The values of extracellular glycerol concentrations found in the present study fit with previous determinations performed in lean and obese subjects (20, 21).
After calibration of the probes, two 15-min fractions of the outgoing dialysate were collected and the subjects performed exercise at a load corresponding to 50% of their individual heart rate reserve for 45 min, on a bicycle ergometer. The load was identical before and at the end of the LCD. The heart rate was continuously monitored with a Baumann BHL 6000 cardiometer during the exercise. After the exercise, subjects rested in the semirecumbent position for 60 min. During the exercise and the recovery periods, 15-min fractions of the dialysate were collected. Water intake was allowed ad libitum during the experimental period.
Before exercise and every 30 min, 10 ml of blood were collected from an indwelling polyethylene catheter inserted into an antecubital vein for plasma determinations. The catheter was kept patent by slow infusion of saline. Blood was collected on 50 µl of an anticoagulant and antioxidant cocktail (Immunotech SA, Marseille, France), to prevent catecholamine oxidation, and processed immediately in a refrigerated centrifuge. The plasma was stored at -80 C until analysis.
After completing the investigation days at the beginning of the protocol, the patients were instructed to take a diet providing 500 kcal/d less than their habitual diet, which was estimated by a 7-d weighed food record before the beginning of the study. The average calorie content of the diet was 1250 ± 75 kcal/d. They consulted the dietician every 2 wk.
Drugs and analytical methods
Phentolamine methanesulfonate (Regitine) was obtained from Ciba-Geigy (Reuil-Malmaison, France). Glycerol in dialysate (10 µl) and in plasma (20 µl) was analyzed with an ultrasensitive radiometric method (22). Ethanol in dialysate and perfusate (5 µl) was determined with an enzymatic method (23). Plasma glucose was determined with a glucose-oxidase technique (Biotrol kit, Merck-Clevenot, Nogent-s-Marne, France) and NEFA by an enzymatic procedure (Wako kit, Unipath, Dardilly, France). Plasma insulin concentrations were measured using RIA kits from Sanofi Diagnostics Pasteur (Marnes la Coquette, France). Plasma epinephrine and norepinephrine were assayed in 1-ml aliquots of plasma by HPLC using electrochemical (amperometric) detection. Quantification of 2-AR, ß2-AR, HSL, and cyclophilin mRNA levels was performed by RT-competitive PCR as previously described (24). The RT step was performed on 100 ng of total RNA with a specific antisense primer and Omniscript reverse transcriptase (QIAGEN). cDNA was then amplified by PCR using sense and antisense primers in the presence of known amounts of a specific DNA competitor (Table 1
). DNA competitors were obtained by a deletion in the native sequences using a two-step overlap extension method. PCR products were separated by capillary electrophoresis and quantified using the ABI PRISM 310 Genetic Analyzer system with the Genescan program (Applied Biosystems, Foster City, CA). 2-AR, ß-AR, and HSL mRNA levels were normalized with cyclophilin mRNA levels.
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All the values are means ± SEM. The responses to exercise were analyzed using a paired t test and ANOVA, when appropriate. During exercise, plasma and extracellular response curves were calculated as the total integrated changes over baseline values [area under the curves (AUC)] using the trapezoidal method; P < 0.05 was considered statistically significant.
Results
General observations
Clinical characteristics of the subjects before and at the end of LCD are shown in Table 2. LCD induced weight loss and fat loss with a loss of abdominal adipose tissue as estimated from waist circumference. There was no change in peak oxygen consumption during the diet. Resting plasma values of biological variables are shown in the first column of Table 3. No changes in concentrations of plasma NEFA, glycerol, glucose, insulin, epinephrine, norepinephrine, or lactate were observed in response to LCD. The average load during the exercise was 62.3 ± 2.8 Watts before as well as at the end of the diet, the average heart rate at the end of the exercise bout was 131.3 ± 3.0 before LCD and 134.2 ± 3.0 at the end of LCD.
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Resting values.
At rest, the extracellular glycerol concentrations (EGC) in SCAAT were not different before and at the end of LCD in the control probes (155.1 ± 16.3 vs.125.6 ± 9 µmol/liter) Table. 2
. In both situations, adipose tissue glycerol levels at rest were higher than that in venous plasma. In the probes containing phentolamine, the resting EGCs were significantly higher compared with the control probes with, again, no difference observed between the beginning and the end of the diet (197.8 ± 15.4 and 195.0 ± 17.1,) before and at the end of LCD, respectively.
Exercise.
Before LCD, the EGC increased in the control probe during exercise; the increase being significant from the 15th min of exercise, and reached 370 ± 49 µmol/liter at the 45th min (Fig. 1). The exercise-induced glycerol increase in the probe with phentolamine was higher when compared with the control probe: the EGC reached 522 ± 56 µmol/liter at the 45th min. The calculated average AUC for glycerol increase over 45-min exercise was significantly higher in the probe containing phentolamine than in the control probe (9211 ± 1223 vs. 5831 ± 729 µmol·liter-1·60 min-1, P < 0.004).
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). The exercise-induced glycerol increase in the probe with phentolamine was quite similar when compared with the control probe. The calculated average AUC for glycerol increase over 45-min exercise was not significantly different in the probe with phentolamine than in the control probe (6475 ± 876 vs. 5526 ± 760 µmol·liter-1·60 min-1, P < 0.19). Effect of LCD on sc adipose tissue blood flow at rest and during exercise
Adipose tissue blood flow was assessed by ethanol outflow/inflow ratios (ethanol concentration measured in the dialysate divided by the ethanol concentration measured in the perfusate x 100 from the two probes. The results are reported in Fig. 2. At rest no differences were observed in the ethanol outflow/inflow ratio in either probe before or at the end of LCD. During exercise, the ethanol outflow/inflow ratio decreased (P < 0.05) in both probes before and at the end of LCD and no significant differences of the ethanol outflow/inflow ratio were observed during the exercise bout either in the control probe or in the probe with phentolamine (Fig. 2).
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At rest, the dialysate lactate concentrations were not different before and during LCD in the control probe (0.21 ± 0.02 and 0.23 ± 0.03 mmol/liter, respectively) or in the probe with phentolamine (0.24 ± 0.04 and 0.22 ± 0.03 mmol/liter, respectively). The calculated extracellular lactate concentrations were similar to plasma values (Fig. 3 and Table 3). During exercise, the increase of lactate concentrations in SCAAT paralleled that observed in plasma. The response to exercise was not different before or at the end of LCD, and phentolamine had no effect on lactate concentration in SCAAT (Fig. 3).
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Resting plasma NEFA and glycerol concentrations were not different before and at the end of LCD (Fig. 4). In both situations, plasma NEFA concentrations decreased during the first 15 min of exercise and then progressively increased until the end of the exercise bout and remained elevated 30 min after the end of the exercise bout. During exercise, no difference was found in the time course of the plasma NEFA concentration changes before and during LCD. The plasma glycerol level increased 15 min after the beginning of exercise in both groups and peaked at the 45th min of exercise. During recovery, it decreased to values similar to those found in basal conditions. The plasma glycerol concentration was higher at the 45th min of exercise at the end of LCD compared with the prediet condition. However, the calculated average AUC for glycerol increase over 45 min of exercise was not significantly different before and during LCD (2758 ± 645 vs. 3072 ± 481 µmol·liter-1·60 min-1, P < 0.33).
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At rest, plasma catecholamines, glucose, insulin and lactate concentrations were found unchanged during the LCD (Table 3). Plasma catecholamine levels increased during the exercise, and there were no differences between the plasma values during exercise, before and at the end of LCD. The whole response to exercise, as assessed using AUC over 45 min were unchanged. The time-course of changes in the concentrations of the other plasma parameters studied were not different before and at the end of LCD, namely the increase in lactate and glucose concentrations and a slight decrease in plasma insulin.
Effect of LCD on 2-AR and ß-AR mRNA levels
2-AR, ß2-AR, HSL, and cyclophilin mRNA were quantified using RT-competitive PCR in 8 subjects before and during LCD. Individual variations in 2-AR mRNA levels are shown in Fig. 5. The level of 2-AR mRNA, normalized to the cyclophilin mRNA level, was significantly decreased during LCD (0.05 ± 0.01 vs. 0.08 ± 0.02, P < 0.01). No change was observed for ß2-AR mRNA levels (0.012 ± 0.003 vs. 0.013 ± 0.002) or HSL mRNA levels (0.33 ± 0.03 vs. 0.31 ± 0.06).
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The present findings show that the 2-adrenergic receptor is involved in the regulation of lipolysis in SCAAT during exercise in obese women and that its activation during exercise produces an antilipolytic effect. The involvement of 2-ARs in the control of lipolysis was shown by the enhancement of exercise-induced lipolysis produced by local perfusion of the 2-AR-antagonist, phentolamine, as previously demonstrated (16, 17, 25). The main finding of the study is that hypocalorie diet suppressed the 2-mediated antilipolytic activity during exercise; this phenomenon was associated with a reduction of 2-AR mRNA levels of in adipose tissue.
In a previous study carried out in obese men, we found that exercise-induced lipid mobilization (60 min at a similar relative power, i.e. 50% of the heart rate reserve), was largely impaired in SCAAT in obese compared with normal subjects (17). The physiological stimulation of adipocyte 2-ARs during exercise contributes to this impairment because phentolamine enhanced (about 4.3-fold) exercise-induced lipid mobilization in SCAAT, the enhancement being markedly higher than in lean subjects. In the present study, the exercise-induced increase in EGC was found in obese women and the blockade of 2-ARs by phentolamine enhanced (1.5-fold) the lipid mobilization in SCAAT. The exercise-induced response of EGC was higher in obese women than in obese men as observed in our previous study. However, in the present study, women exercised 45 instead of 60 min at a similar relative power, i.e. 50% of their heart rate reserve but at a lower mean load. Although additional studies are required to firmly establish the validity of these discrepancies, such a gender-related difference has also been reported in young nonobese subjects by Hellström et al. (25). There may be several mechanisms that could putatively be responsible for the gender differences observed in lipid mobilization during exercise in SCAAT. Concerning fat cell adrenergic receptors, numerous comparative gender-related studies on human fat cell responsiveness to catecholamines have been carried out in vitro. Comparative studies on fat cells from SCAAT of nonobese subjects showed that ß-AR-induced lipolysis is higher in women than in men and that conversely, the 2-AR-dependent antilipolytic effect of epinephrine was more marked in women (26). However, other results have shown that ß- and 2-adrenergic responsiveness were not noticeably different whatever the sex in obese subjects (27). In the SCAAT deposit, the number of 2-ARs is at least 5–6 times higher than that of ß-ARs. So, differences in 2- and ß-AR expression cannot explain the large gender differences found in the 2-AR responsiveness during a physiological activation of the SNS in obese subjects. Insulin and sympathetic nervous system activation could contribute to these differences. When considering insulin and norepinephrine plasma levels, insulin decreased as expected while the increment in plasma norepinephrine levels was similar to that previously reported in obese men. The most striking difference observed in obese women concerns the minor changes affecting plasma epinephrine levels which only increased from 11 ± 1 to 44 ± 8 pg/ml after 45 min of exercise in obese women. The basal and stimulated values were noticeably higher (59 ± 21 for basal levels and 130 ± 19 and 178 ± 38 pg/ml after 30 and 60 min of exercise, respectively) in obese men (17). It could be proposed that the larger increase in lipid mobilization observed in women SCAAT during exercise is closely related to a weaker 2-adrenergic effect, linked to a reduced elevation in plasma epinephrine concentration. Previous studies by our group have focused upon the role epinephrine could play in the initiation of 2-AR-mediated antilipolytic effects. First, epinephrine is the amine that exhibits the highest affinity for fat cell 2-ARs (4). Secondly, we have demonstrated that in men, the 2-AR-dependent antilipolytic effect is stronger when plasma levels of epinephrine are increased during exercise (16). To sum up, epinephrine seems to be the hormone that initiates the strongest 2-AR-mediated action when secreted. The weakest 2-adrenergic effect observed in SCAAT of obese women is probably related to the lower plasma epinephrine levels that do not reach the threshold for 2-AR activation.
The second part of the present study is focused on the impact of LCD. The lack of exercise-induced 2-AR antilipolytic effect in SCAAT after LCD (Fig. 1) could be partly explained by the reduction of 2-AR mRNA expression in SCAAT. However, it should be taken into account that the change in 2-AR mRNA expression does not mean that receptor protein has changed as well. The exercise load was identical before and at the end of LCD and exercise-induced increment in plasma catecholamine levels were unchanged after LCD. However, the reduction of the 2-AR-dependent antilipolytic effect during LCD was not associated with an increased glycerol production in SCAAT during exercise. Higher plasma glycerol levels were found at the end of the exercise bout at the end of LCD. To interpret the present results, metabolic factors must be considered with blood flow determinations. It can be proposed that under LCD, the balanced interplay between activation of ß- and 2-AR pathways is modified in SCAAT. LCD promotes reduction of the 2-AR component leading to the privileged activation of the ß-AR pathway. In the present study, the subjects were submitted to moderate calorie restriction (5 MJ/d) for 12 wk, and it is postulated that the LCD reduced the 2-AR pathway without changes in the ß-adrenergic pathway. Another explanation for the minor changes of circulating glycerol and NEFA occurring in response to exercise during LCD is that LCD may improve the clearance of these metabolites at muscle and hepatic levels. For example, a previous investigation has demonstrated that energy restriction increased uptake of glycerol for neoglucogenesis, particularly in obese subject (28). Our in vivo results are in accordance with the results of previous in vitro studies on obese SCAAT fat cells studied before and after a 15-wk weight reducing program (27). It was shown that the 2-AR-dependent antilipolytic effect was reduced after an average 9–10 kg weight loss and 15–20% decrease in fat cell weight.
Changes in local blood flow could also influence the concentration of the interstitial metabolites. It is an important variable in microdialysis studies (29). Exercise-induced vasodilatation was not enhanced during LCD (Fig. 2). Moreover, in the presence of phentolamine (1/2-AR antagonist), the exercise-induced vasodilatation was not different and LCD did not apparently change the ethanol ratio at rest or during exercise. Although phentolamine is known for its 1/2 blocking properties, the present results did not show any significant difference whatever or not the presence of phentolamine in the probes. The vasodilating action predominates during exercise, suggesting a preeminence of ß-AR-dependent effect in vascular bed of adipose tissue. Ethanol-based microdialysis cannot bring a reliable quantitative estimation of blood flow changes in adipose tissue. It cannot be excluded that the drop in ß-AR-dependent glycerol output occurring after LCD (decreased 2-AR-mediated effect is expected to improve ß-AR-dependent lipid mobilization) is related to local blood flow modifications. Thus, the vasodilatation could modulate the positive action of exercise on lipolysis in SCAAT because an increment of glycerol drainage in the circulation was simultaneously promoted with the stimulation of lipolysis (Fig. 2).
It has often been suggested that lactate could inhibit lipid mobilization especially at high concentrations, up to 3 mmol/liter (30, 31, 32). However, a study has shown that, even at high concentrations, lactate (infused in a microdialysis probe) did not modify the glycerol production in human SCAAT during exercise (32). In the present study, plasma lactate concentrations rose to 1.7–1.8 mmol/liter during exercise and no difference was found before or during LCD and during exercise. A similar rise in lactate concentration was observed in SCAAT before and during LCD. This rise was weakly (but not significantly) reduced about 17–18% before and during LCD by phentolamine (Fig. 4). So, a modification of glycerol releasing activity by lactate, if any, cannot be argued from the present results.
In conclusion, the present study demonstrates that the negative energy balance produced by hypocalorie diet reduces the expression of the 2-AR gene in adipose tissue in obese women and reduces the physiological function mediated by the 2-AR—i.e., the 2-AR-mediated antilipolytic action during exercise. Hence, the nutrient-gene interaction observed in this study was associated with a change of the gene-regulated physiological function and a cause-effect relationship can be presumed. Moreover, the same relationship was discerned between ß2-AR expression and the corresponding physiological function in SCAAT: the hypocalorie diet did not change ß2-AR expression and, correspondingly, the ß-AR-mediated stimulation of lipolysis was not changed during the diet. These results fit with a previous report demonstrating that in obese women, the weight loss induced by very LCD was stronger when the 2-AR sensitivity was the weaker in isolated fat cells; the 2-AR responsiveness may be predictive of weight loss during very LCD (33). It remains to be demonstrated whether the same effect of LCD could be produced in obese men, taking into account that the antilipolytic action mediated by 2-ARs during exercise is stronger in obese men compared with women. It also remains to be established if the smaller rise in plasma epinephrine occurring during exercise in obese women is truly responsible for the weaker 2-AR stimulation, as proposed from the study. The present findings suggest possible pathways for pharmacological approaches to promote higher mobilization of lipids from lipid stores during exercise in obese subjects.
Acknowledgments
We express our gratitude to Z. Pariskova and M.-T. Canal for their contribution to the study.
Footnotes
The study was financially supported by a grant from the Grant Agency of Czech Republic (GACR 303/0649), the Commission of the European Communities RDT program (FATLINK: Dietary fat, body weight control, and links between obesity and cardiovascular disease), the Fondation pour la Recherche Médicale, and by the Direction Générale de la Coopération Internationale et du Développement (Program d’Action Intégré Franco-Tchèque).
Abbreviations: AR, Adrenergic receptor; AUC, area under the curve; 2-AR, 2-adrenoceptor; ß2-AR, ß2-adrenoceptor; EGC, extracellular glycerol concentration; HSL, hormone-sensitive lipase; LCD, low calorie diet; NEFA, nonesterified fatty acid; SCAAT, sc abdominal adipose tissue; SNS, sympathetic nervous system.
Received September 13, 2001.
Accepted December 12, 2001.
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) added to the perfusion medium. Data are expressed as means ± SEM. A statistical comparison of the values was first performed by two-way ANOVA for repeated measures with diet (before and during LCD) and time as factors of the analysis. Subsequently, the effects of exercise were analyzed before and during LCD by one-way ANOVA with time as factor of the analysis, followed by a Bonferroni-Dunett posthoc test, taking basal values as control. *, P < 0.05 when compared with baseline value.
