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-adrenergic desensitization in human adipose
tissue
1 Laboratory of the Adaptations to Exercise, Purpan University Hospital, 31059 Toulouse Cedex; 3 Laboratory of Medical and Clinical Pharmacology, Faculty of Medicine, 31073 Toulouse Cedex; 2 Institut National de la Santé et de la Recherche Médicale Unité 317, Rangueil University Hospital, 31062 Toulouse Cedex 4, France; and 4 Department of Sports Medicine, Third Faculty of Medicine, Charles University, 100 00 Prague, Czech Republic
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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This study was designed to assess whether
physiological activation of the sympathetic nervous system induced by
exercise changes adipose tissue responsiveness to catecholamines in
humans. Lipid mobilization in abdominal subcutaneous adipose tissue was studied with the use of a microdialysis method in 11 nontrained men
(age: 22.3 ± 1.5 yr; body mass index: 23.0 ± 1.6). Adipose tissue adrenergic sensitivity was explored with norepinephrine, dobutamine (
1-agonist), or terbutaline
(2-agonist) perfused during 30 min through probes before
and after 60-min exercise (50% of the maximal aerobic power). The
increase in extracellular glycerol concentration during infusion was
significantly lower after the exercise when compared with the increase
observed before the exercise (P < 0.05, P < 0.02, and P < 0.01, respectively, for norepinephrine, dobutamine, and terbutaline). In a control experiment realized without exercise, no difference in
norepinephrine-induced glycerol increase between the two infusions was
observed. To assess the involvement of catecholamines in the blunted
-adrenergic-induced lipolytic response after exercise, adipose
tissue adrenergic sensitivity was explored with two 60-min infusions of
norepinephrine or epinephrine separated by a 60-min interval. With both
catecholamines, the increase in glycerol was significantly lower during
the second infusion (P < 0.05). The findings suggest
that aerobic exercise, which increased adrenergic activity, induces a
desensitization in 1- and 2-adrenergic
lipolytic pathways in human subcutaneous adipose tissue.
lipolysis; catecholamines; dobutamine; terbutaline
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE BIOLOGICAL
FUNCTIONS of the sympathetic nervous system (SNS) are mediated by
the activation of 
- and -adrenergic receptors (AR) by
catecholamines. In vitro, the -AR was shown to be regulated by
-agonist agents; when target cells are in the presence of -AR
agonists, the receptors become desensitized within a few minutes. This
phenomenon also occurs in human fat cells, and in vitro studies have
shown that isolated adipocytes exposed to -AR agonists show a
decrease in functional coupling between -AR and adenylate cyclase
(10, 21). Recent studies have demonstrated that
desensitization of the -adrenergic response in rat adipocytes involves various receptor subtypes and cAMP phosphodiesterase (7). In vivo desensitization of the -adrenergic
response was shown in white adipocytes of various species (12,
22), and a differential regulation of 1- and
2-AR has been described (9, 32). In humans,
during prolonged local epinephrine infusion, concentrations of
interstitial glycerol tend to fall after a transient increase
(2). Stallknecht et al. (34) showed that
prior exposure of adipose tissue to epinephrine induced a decrease of a
subsequent lipolytic effect of the hormone during a second intravenous
epinephrine infusion. These findings suggest that catecholamines induce
desensitization of adipose tissue lipolysis in humans.
Physical activity promotes activation of the SNS and an increase in circulating catecholamine levels in the blood (19). During exercise, glycerol output from subcutaneous adipose tissue (3, 15, 35) and glycerol plasma concentrations (25) are increased. At present, there are no data that demonstrate whether desensitization occurs after a physiological activation of the SNS induced by exercise in humans.
This study was designed to assess whether exercise-induced activation
of the sympathoadrenal system had a functional impact on in situ human
adipose tissue responsiveness to catecholamines and selective -AR
agonists. The study was carried out with the use of the microdialysis
technique (1, 5, 35). This method allows measurement of
extracellular (EC) concentrations of various substances that diffuse
from the interstitium of adipose tissue into the infusion fluid. It
also enables administration of various pharmacologically active
substances into the tissue through the microdialysis probe. In this
study, norepinephrine, dobutamine (1-AR agonist), and
terbutaline (2-AR agonist) through the subcutaneous adipose tissue were infused before and after physical exercise to
assess the exercise-induced desensitization. In control experiments, repeated infusions of epinephrine and norepinephrine, without any
exercise in between, were performed.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects
Eleven nontrained men were selected for this study. Their mean age was 22.3 ± 1.5 yr, and their body mass index was 23.0 ± 1.6 kg/m2. All subjects had a stable body weight for at least 3 mo before the beginning of the study, and all were drug free. The subjects had given their informed consent before the study, which was performed according to the declaration of Helsinki and approved by the Ethical Committee of the University Hospital.Microdialysis Method
The subjects were investigated at 0800 after an overnight fast. They were placed in a semirecumbent position. Two microdialysis probes (Carnegie Medecin, Stockholm, Sweden) of 20 × 0.5 mm and 20,000-MW cutoff were inserted percutaneously after epidermal anesthesia (200 µl 1% lidocaine; Roger-Bellon, Neuilly-s-Seine, France) into the abdominal subcutaneous adipose tissue at a distance of 10 cm from the umbilicus. The probes were separated by 5 cm and were connected to a microinjection pump (Harvard apparatus, S.A.R.L., Les Ulis, France). They were perfused with a sterile Ringer solution [(in mM) 154 sodium, 4 potassium, 2.5 calcium, and 160 chloride] supplemented with ethanol (1.7 g/l). Ethanol was added to the perfusate to estimate changes in the adipose blood flow, as previously described (4, 5). After a 30-min equilibration period, dialysate was collected for 30 min at a flow rate of 0.5 µl/min. Then, the probes were perfused at 2.5 µl/min for the remaining experimental period. The estimated glycerol EC concentrations were calculated by plotting (after log transformation) the concentration of glycerol in the dialysate measured at 0.5 and 2.5 µl/min against the infusion rates. The values given in RESULTS fit with previous determinations in lean subjects (4, 5, 24). According to the experimental schedule, various catecholamines or selective1- or 2-AR agonists (dobutamine and
terbutaline, respectively) were added to the perfusate. During the
whole experiment, dialysate was collected every 15 min, except during
the 30-min adrenergic agent infusions where dialysate was collected
every 10 min. The fractions were kept on ice; glycerol and ethanol
analysis was performed in each fraction collected. The changes in
nutritive blood flow were assessed using the ethanol outflow/inflow
ratio measurement, as previously described (17, 20).
Experimental Schedule
First experiment.
After calibration of the two probes, six subjects were infused for 30 min with Ringer solution containing either 10 µM of norepinephrine
(Sterling-Wintrop, Gentilly, France), 100 µM of the selective
1-AR agonist dobutamine (Dobutrex, Lilly France SA,
France), or 100 µM of the selective 2-AR agonist
terbutaline (Bricanyl, Astra, France). After that, the probes were
infused for 60 min with the Ringer solution. Then, the subjects
performed a cycling exercise for 60 min. After that, they were allowed
to rest in the semirecumbent position for 60 min. The probes were infused again for 30 min with Ringer solution containing either 10 µM
of norepinephrine, 100 µM of the selective dobutamine, or 100 µM of
terbutaline. Finally, the probes were infused for 60 min with the
Ringer solution while the subjects maintained the semirecumbent
position (Figs. 1A and
2, A and B). A
control investigation was carried out on the same subjects, with
similar timing and norepinephrine infusion, but without the exercise
period (Fig. 1B).
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Second experiment.
After calibration of the two probes, five subjects were infused for 60 min with Ringer solution containing either 10 µM norepinephrine or 10 µM epinephrine (epinephrine, Aguettant, Lyon, France). After that,
the probes were infused with the Ringer solution during 60 min. The
probes were infused again for 60 min with Ringer solution containing
either 10 µM norepinephrine or 10 µM epinephrine. Finally, the
probes were infused for 60 min with the Ringer solution. In this second
experiment, dialysate was collected every 15 min (Fig. 3, A and B).
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Exercise
In the first experiment, the subjects performed an exercise for 60 min on a cycle ergometer (Ergo-metrics 800S Ergo-line, Jaeger, Germany). The imposed power corresponded to 50% of the maximal aerobic power. The heart rate was continuously monitored with a Polar Accurex Plus cardiometer (Monitor, France) during the exercise. In all the protocols, the exercise bout was started 60 min after the end of infusion with adrenergic agents so that the increased EC levels after the pharmacological stimulation were back at baseline.Blood samples were drawn from an indwelling polyethylene catheter
introduced into an antecubital vein 10 min before the exercise and
every 15 min during the exercise and recovery for glycerol, nonesterified acids, lactate, glucose, insulin, and catecholamine assays. Blood was immediately centrifuged at 0°C, and the
plasma was stored at 
80°C until analysis.
Analytic Methods
For each investigation, two probes were inserted, and the glycerol and ethanol results were the mean of the values of the two probes. Glycerol in dialysate (10 µl) and in plasma (20 µl) was analyzed with an ultrasensitive radiometric method (8); the intra- and interassay variabilities were 5 and 9.2%, respectively. Ethanol in dialysate and in perfusate (5 µl) was determined with an enzymatic method (6); the intra- and interassay variabilities were 3 and 4.5%, respectively. Plasma nonesterified fatty acids (NEFA) and lactate were determined with an enzymatic procedure (Wako, Unipath, Dardilly, France) and an automated analyzer (YSI 27, Bioblock Scientific, Illkirch, France), respectively. Plasma glucose was determined with a glucose oxidase technique (Biotrol, Merck-Clevenot, Nogent-sur-Marne, France). Plasma immunoreactive insulin was measured with the use of an RIA kit from ERIA Diagnostics Pasteur (Marnes-la-Coquette, France). Plasma epinephrine and norepinephrine were assayed in 1-ml aliquots of plasma by high-pressure liquid chromatography with the use of electrochemical (amperometric) detection (26); the detection limit was 20 pg/sample, day-to-day variability was 4%, and within-run variability was 3%.Statistical Analysis
All the values are expressed as means ± SE. The responses to perfusions were analyzed with the use of a paired t-test. During perfusions, the EC glycerol concentration response and ethanol ratio value were calculated as the total integrated changes over baseline values [area under curve (AUC) from time (t) = 15 to t = 45 min and t = 225 to t = 255 min for the first experiment and from t = 15 to t = 75 min and t = 135 to t = 195 min for the second experiment]. AUC was calculated with the use of a trapezoidal method. Significant values are quoted in Tables 1 and 2. P < 0.05 was considered statistically significant.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Effect of Exercise on EC Glycerol Concentrations and Ethanol Ratio Induced by Local Norepinephrine Infusion in Adipose Tissue
The first infusion of norepinephrine that was started 90 min before the exercise induced a significant increase of EC glycerol by 319 ± 93 µM after a 30-min infusion (Fig. 1A). Norepinephrine infusion promoted a vasoconstriction as shown by the observed increase (+5.8 ± 1.9%) in the ethanol outflow/inflow ratio. At the beginning of the exercise bout (60 min after the end of infusion), the EC glycerol concentration was back at baseline. Moreover, the baseline ethanol outflow/inflow ratio was not significantly different to that before the norepinephrine infusion. During the exercise, significant increases in EC and plasma glycerol, plasma norepinephrine, and epinephrine levels were observed after 30 and 60 min of exercise (Table 1). Plasma NEFA and glucose levels were unchanged, and a significant decrease in insulin plasma level was observed after 60 min of exercise (Table 1). Plasma lactate levels were not significantly increased at the end of exercise. All the above-mentioned parameters as well as EC glycerol concentration and ethanol outflow/inflow ratio returned to levels not different from baseline after 60 min of recovery. The second infusion of norepinephrine, starting 60 min after the end of the exercise, induced an increase in EC glycerol concentration of 149 ± 12 µM. The overall response, when evaluated from the AUC, was significantly lower than during the first infusion (Table 2).In a control experiment, two 30-min norepinephrine infusions separated by 180 min were carried out, but no exercise was performed by the subjects. In these conditions, the increase in EC glycerol concentrations induced by norepinephrine was similar during both infusions. Moreover, norepinephrine infusion promoted a similar increase in ethanol ratio, indicating a similar vasoconstriction (Fig. 1B). The calculated AUC values for the variations of glycerol and ethanol ratio were not different (Table 2).
Effect of Exercise on EC Glycerol Concentrations and Ethanol Ratio Induced by Terbutaline or Dobutamine Infusion in Adipose Tissue
To further the study of the selective pathways involved in the lipolytic modifications observed with norepinephrine, similar experimental protocols were performed with the use of an infusion of either a selective1-AR agonist (dobutamine) or a
selective 2-AR agonist (terbutaline). Dobutamine
infusion induced an increase in glycerol concentration in the EC
compartment; the increase was of 286 ± 74 µM after a 30-min
infusion (Fig. 2A). After cessation of dobutamine infusion,
EC glycerol concentrations fell steadily to reach basal level. The
glycerol released in the EC compartment during the second infusion of
dobutamine was found to be significantly lower (+127 ± 25 µM)
than during the first one (Table 2). Dobutamine infusion promoted
discrete vasodilatation (3.6 ± 2.2% of the ethanol
outflow/inflow ratio). The second dobutamine infusion decreased the
outflow/inflow ratio similar to the first one (2.9 ± 2.7%);
the AUC values for ethanol ratio variations were not different (Table
2).
Terbutaline infusion induced an increase in glycerol concentration in
the EC compartment; the increase was of 336 ± 42 µM after a
30-min infusion (Fig. 2B). After cessation of terbutaline infusion, EC glycerol concentrations fell steadily to reach basal level. During the second terbutaline infusion, the increase of EC
glycerol concentration was 234 ± 55 µM after a 30-min infusion. The glycerol released in the EC compartment during the second infusion
of terbutaline was found to be significantly lower than during the
first one (Table 2). Terbutaline infusion promoted vasodilatation as
shown by the observed decrease (10.5 ± 3.2%) in the ethanol
outflow/inflow ratio. The second terbutaline infusion decreased the
outflow/inflow ratio similar to the first one (11.7 ± 2.1%); the AUC values for ethanol ratio variations were not different (Table 2).
Effect of a Repeated Local Infusion of Norepinephrine and Epinephrine on the Variations of EC Glycerol Concentrations and Ethanol Ratio
To investigate the putative desensitizing effect of catecholamine on adipose tissue during exercise, two subsequent 1-h norepinephrine or epinephrine infusions (separated by a 1-h interval) were performed, and glycerol responses were evaluated. Norepinephrine infusions induced an increase in glycerol concentration in the EC compartment (Fig. 3A). The EC glycerol concentration increase during the second infusion was significantly lower than the first one (204 ± 35 vs. 270 ± 71 µM after 60-min infusion), and the AUC values for glycerol variations were different (Table 2). Norepinephrine infusion promoted vasoconstriction as shown by the observed increase in the ethanol outflow/inflow ratio (17.0 ± 5.2 and 16.6 ± 6.0% after 60-min infusion). This increase was similar for both infusions, with AUC values for the variations of the ethanol ratio not being different (Table 2).Epinephrine infusions induced an increase in glycerol concentration in the EC compartment (Fig. 3B). The EC glycerol increase during the second infusion was significantly lower than the first one (395 ± 78 vs. 464 ± 75 µM after 60-min infusion), and the AUC values for glycerol variations were different (Table 2). Epinephrine infusion promoted vasoconstriction as shown by the observed increase in the ethanol outflow/inflow ratio (25.7 ± 8.7 and 20.3 ± 7.6% after 60-min infusion). This increase was similar for both infusions, with AUC values for the variations of the ethanol ratio not being different (Table 2).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The present study shows for the first time that physiological
activation (physical exercise) of the SNS induces desensitization of the adrenergic lipolytic response to local perfusion of
catecholamines in subcutaneous adipose tissue in humans. It has been
largely demonstrated through in vitro studies on isolated fat cells
(14), dialysis studies (4), and binding
studies (29) that 1- and 2-AR coexist in human adipose tissue and are both
desensitized by adrenergic stimulation.
Our results fit with animal studies showing that sustained adrenergic
tone leads to -AR adipose tissue desensitization (12, 38). In vitro studies have shown that desensitization of the -adrenergic response occurs in isolated rat adipocytes after acute
exposure to isoproterenol (7) and that the activation of
cAMP phosphodiesterase is in fact responsible for the desensitization of norepinephrine response as well as for selective -AR-mediated responses. More recently, studies on isolated human adipocytes have
shown similar results (unpublished data), and several lines of evidence
support the view that -AR in human fat cells is desensitized by
prior in vitro exposure to -adrenergic agonists and that the desensitization is associated to a downregulation of -AR (10, 27). In contrast, Wahrenberg et al. (40)
and Savard et al. (33) found that the lipolytic response
to catecholamines was increased by 20-35% after an exercise bout
on a cycle ergometer. However, in these studies, the adrenergic
stimulation was performed by physical exercise just before adipocyte
isolation from the adipose tissue. The removal of adipocytes from their
actual environment (other cells and plasma factors) before
(7) or after (33, 40) the catecholamine
stimulation could explain the discrepancy between these studies. Other
in vitro studies have found no modification of the isoprenaline or
norepinephrine-induced lipolysis in subcutaneous isolated adipocytes
after a 100-min exercise in trained or sedentary women
(13). On the other hand, the influence of exercise on catecholamine-stimulated lipolysis is known to be location dependent in
humans; 30-min submaximal exercise increased -adrenergic-induced lipolysis of gluteal adipose tissue (40), but the same
exercise did not enhance catecholamine-stimulated lipolysis in
abdominal adipocytes (39).
In our in situ study, the exercise blunted the lipolytic response of
adipose tissue to norepinephrine as well as to the selective 1- and 2-adrenergic agonists. Our results
did not fit with those of Wahrenberg et al. (40) and
Savard et al. (33). But in their experiments, the
removal and the study of the catecholamine-stimulated lipolysis of
adipocytes were performed straight after the exercise period, whereas
in our work adipose tissue lipolytic response was evaluated in situ
after 1-h recovery. We can suggest that, in our study, the length of
adipocyte hormonal impregnation could alter their responsiveness to
catecholamines. The blunted -adrenergic lipolytic response appeared
to be consecutive to exercise practice, because -adrenergic
stimulation was decreased when norepinephrine was infused 1 h
after 60 min of exercise. As a control, the experiment described in
Fig. 1B was carried out to show that the responsiveness to
norepinephrine was similar when it was infused twice separated by a 3-h
interval without exercise. Although lipolytic responses during the
first norepinephrine infusion differed between the two experiments
(Fig. 1, A and B), this difference did not alter our results. Indeed, we only compared lipolytic responses over the same
1-day experiment because it is well known that adipose tissue
responsiveness can differ from day to day for the same subject.
Moreover, the probes were not inserted strictly in the same place in
the abdominal adipose tissue.
We presume that desensitization resulted from the exposure of adipocytes to increased concentrations of catecholamine during the physical exercise. Nevertheless, other factors could also explain the desensitization. Plasma insulin rebound occurring at the end of exercise could be responsible for an extended antilipolytic effect. Lactate level increase during exercise could also be involved in this phenomenon, although Trudeau et al. (37) have shown recently that lipolytic response in abdominal subcutaneous adipose tissue was not affected by local lactate perfusion. In a previous study, Stich et al. (35) showed that during two identical successive exercise bouts separated by 1 h of recovery, the lipolytic responsiveness was higher during the subsequent exercise bout. However, the increase of plasma epinephrine was dramatically higher, and the insulin level was lowered during the second exercise bout compared with the first one. Therefore, the two-exercise design was not appropriate to reveal possible desensitization. Consequently, we chose to perfuse catecholamine locally before and after the physiological activation. Our previous studies have shown that direct infusions in the subcutaneous adipose tissue of either norepinephrine or epinephrine at 10 µM (30) induced similar lipolytic responses compared with a physiological stimulation by exercise (15).
To assess the effect of catecholamine alone, exercise was replaced by
60-min infusions of epinephrine or norepinephrine (Fig. 3, A
and B). Identical patterns to those from exercise
stimulation were found, i.e., a reduced lipolytic response during the
second infusion period compared with the first one. This result
confirms that the effect of exercise on desensitization could result
from the exposure of adipocytes to increased concentrations of
catecholamine. The fact that the desensitization of human fat cells
found in our study was relevant to catecholamine increase during
exercise is also supported by the experiments of Stallknecht et al.
(34). These authors found that epinephrine infused
intravenously led to increased lipolysis in subcutaneous adipose tissue
(evaluated by the microdialysis method) and that the lipolytic response
was markedly decreased during repeated exposure to epinephrine. Another study by Klein et al. (25) did not find changes in
lipolysis induced by 1-h epinephrine infusion, 90 min after 1 h of
strenuous exercise (performed at 70% maximal O2
consumption on endurance-trained athletes), compared with
epinephrine-induced lipolysis without exercise. However, this study
investigated lipolysis through the rate of appearance of glycerol in
plasma, which reflects whole body lipolysis, and the experiment was
performed on endurance-trained athletes. These differences with our
study, which used subcutaneous adipose tissue microdialysis in
sedentary subjects, could explain the lack of desensitization found by
Klein et al. (25). Exercise intensity can also influence
adrenergic response to desensitization; indeed, it was shown that
cardiovascular -adrenergic response was blunted after high-, but not
low-, intensity prolonged exercise (28).
Moreover, our results showed that the decrease in -AR-induced
lipolysis occurred with 1-AR (dobutamine) and
2-AR (terbutaline). These data do not entirely fit with
the findings of Arner et al. (2), who demonstrated that a
desensitization phenomenon appeared when isoprenaline, epinephrine, or
norepinephrine were infused in adipose tissue for 2 h through the
microdialysis probe and that this desensitization was found for
1-AR (dobutamine) but not for 2-AR
(terbutaline). The molecular mechanisms involved in the regulation of
1- and 2-AR could explain the observed desensitization of the 1- and 2-AR
responsiveness. One mechanism involves the phosphorylation of the
receptor occupied by 1- or 2-agonist, by
-adrenoceptor kinase, and by G protein-receptor kinase. Although
most works have been done with the 2-AR, it is clear
that the 1-AR can also be similarly phosphorylated
(36). Another process, involving the consensus sites
contained in 1- and 2-AR, is the
phosphorylation of the receptor by second messenger kinase (PKA, PKC).
These mechanisms could also participate in the sequestration of the
receptors to an intracellular compartment (36). This last
phenomenon (downregulation) leads to a decrease in the density of
functional receptors, and it occurs more slowly than the first mechanism.
No data are available concerning the modification of the -AR number
in adipose tissue induced by exercise. However, it has been
demonstrated that dynamic exercise induces the translocation of -AR
from intracellular sites to the cell surface in human lymphocytes
(18) and in rat myocardium (23). Butler et
al. (11) showed that lymphocyte -AR responsiveness
after exercise was biphasic. Indeed, there was an initial increase of
isoprenaline-stimulated cAMP production by lymphocytes immediately
after exercise and a decrease thereafter. From these different
observations, it is tempting to speculate that this process occurs in
fat cells and could also explain the difference found when adipose
tissue is investigated in vitro or in our in vivo experiment.
Local microcirculation has been shown to influence glycerol levels in
adipose tissue (16, 20). The measurement of ethanol escape
through the dialysis probe is a validated nonquantitative method to
estimate the changes in vasomotricity induced by adrenergic agonists in
adipose tissue (4, 5, 20). In accordance with previous
findings, the present study found that norepinephrine perfusion
increases the ethanol outflow/inflow ratio, indicating vasoconstriction, and, oppositely, that terbutaline or dobutamine decreases the ethanol outflow/inflow ratio, indicating vasodilatation (5, 30). The present study did not provide evidence that exercise induces a change in adipose tissue blood flow. This suggests that the modifications of interstitial glycerol before and after exercise were influenced, if at all, in the same manner by perfused adrenergic agents. Consequently, the lowered lipolytic response observed after the exercise indicates a true decrease of
-adrenergically mediated lipolysis in adipose tissue.
In conclusion, 1 h after a single bout of physical exercise, the
lipolytic response of subcutaneous adipose tissue to catecholamine action is blunted. This decrease accounts for physiological -AR desensitization. This phenomenon seems to depend on increased adrenergic activity occurring during exercise.
Perspectives
To study subcutaneous adipose tissue-desensitization in situ
without perfusion of any pharmacological agents, we need to find a
physiological model inducing two identical successive activations of
the SNS. With exercise, it is quite easy to produce two similar activations of the SNS, and plasmatic norepinephrine level suggests that exercise intensity does not change during the two exercise bouts.
However, previous data have shown that during a double successive
aerobic exercise at 50% 
O2 max
separated by 1-h recovery, plasma epinephrine was significantly higher
during the second bout of exercise (35). This might be due
to hypoglycemia relative to the first exercise and glycogen needs for
the second bout of exercise. Indeed, we have already shown that
saccharose ingestion during exercise decreased the plasmatic
epinephrine level (15), and it is well known that
epinephrine acts as a hyperglycemic hormone during exercise. Therefore,
fed compared with fasting subjects could be an interesting
physiological model to reveal -desensitization.
On the other hand, we have also shown (unpublished data) that aerobic
exercise at 50% of O2 max performed by
endurance-trained subjects did not induce the epinephrine increase
during the second bout of exercise, and, consequently, there was no
significant difference between the two successive exercise-induced
plasma catecholamine levels. Therefore, trained subjects appear
to be another interesting physiological model to show
-desensitization.
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ACKNOWLEDGEMENTS |
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The authors wish to express gratitude to Marie-Thérèse Canal for contributing to the study.
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FOOTNOTES |
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This work was supported by Grant 3611-2 of the Czech Ministry of Health, the Commission of the European Communities specific RTD program CT98-4141 (FATLINK: dietary fat, body weight control, and links between obesity and cardiovascular disease), and the Fondation pour la Recherche Médicale.
Address for reprint requests and other correspondence: I. De Glisezinski, Service d'Exploration de la Fonction Respiratoire et de Médecine du Sport, CHU Purpan, 31059 Toulouse Cedex, France (E-mail: crampes.f{at}chu-toulouse.fr).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 6 December 1999; accepted in final form 13 September 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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) and the ethanol ratio
(
) in subcutaneous adipose tissue before and after
60-min exercise. Nor was perfused for 30 min, 90 min before exercise,
and 60 min after the cessation of the exercise. Values are means ± SE. The areas under the curves of the Nor-induced increase in
interstitial glycerol concentrations were significantly lower after
exercise (P < 0.05). B: effect of Nor on
the interstitial glycerol levels (
