1 University of Castilla-la Mancha at Toledo, Toledo 45071, Spain; and 2 The Human Performance Laboratory, Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, Texas 78712
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
This study
determined the effects of elevated plasma epinephrine on fat metabolism
during exercise. On four occasions, seven moderately trained subjects
cycled at 25% of peak oxygen consumption (O2 peak) for 60 min.
After 15 min of exercise, subjects were intravenously infused with low
(0.96 ± 0.10 nM), moderate (1.92 ± 0.24 nM), or high
(3.44 ± 0.50 nM) levels (all P < 0.05) of epinephrine
to increase plasma epinephrine above control (Con; 0.59 ± 0.10 nM).
During the interval between 35 and 55 min of exercise, lipolysis
[i.e., rate of appearance of glycerol] increased above Con
(4.9 ± 0.5
µmol · kg
1 · min
1)
with low, moderate, and high (6.5 ± 0.5, 7.1 ± 0.8, and
10.6 ± 1.2
µmol · kg
1 · min
1,
respectively; all P < 0.05) levels of epinephrine despite
simultaneous increases in plasma insulin. The release of fatty acid
into plasma also increased progressively with the graded epinephrine
infusions. However, fatty acid oxidation was lower than Con
(11.1 ± 0.8
µmol · kg
1 · min
1)
during moderate and high levels (8.7 ± 0.7 and 8.1 ± 0.9
µmol · kg
1 · min
1,
respectively; P < 0.05). In one additional trial, the same
subjects exercised at 45%
O2 peak without
epinephrine infusion, which produced a plasma epinephrine concentration
identical to low levels. However, lipolysis was lower (i.e.,
5.5 ± 0.6 vs. 6.5 ± 0.5
µmol · kg
1 · min
1;
P < 0.05). In conclusion, elevations in plasma epinephrine
concentration during exercise at 25% of
O2 peak progressively
increase whole body lipolysis but decrease fatty acid oxidation. Last, increasing exercise intensity from 25 to 45%
O2 peak attenuates the
lipolytic actions of epinephrine.
stable isotopes; indirect calorimetry; lipolysis; free fatty acid kinetics
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
EPINEPHRINE has been used in many situations as a tool to stimulate fat metabolism (12). Intravenous epinephrine infusion has been used to test differences in lipolysis between genders or between fat depots in the same individual (20). Epinephrine has also been used to determine if endurance training increases lipolytic sensitivity (17) and to test if obesity is caused by a reduction in hormonal stimulation of lipolysis (40). The information derived from those studies has greatly helped understanding of the hormonal regulation of lipolysis in humans. However, all of these studies have been conducted on resting humans. Surprisingly, little is known about the whole body lipolytic response to epinephrine administration during exercise.
The increase in lipolysis within subcutaneous adipose tissue with the
transition from rest to mild exercise appears to be stimulated by
epinephrine through beta receptor activation (2) and by the lowering of
plasma insulin (15). However, the pattern with which whole body
lipolysis increases with increased exercise intensity (11) and the
mechanisms by which triglyceride stored within adipose tissue and
within muscle fibers is hydrolyzed remain unclear. It is well known
that fatty acid oxidation increases when exercise intensity increases
from low to moderate levels and that it declines with intense exercise
in association with accelerated carbohydrate metabolism (8, 33). It is
logical that lipolysis might follow the same pattern. Raising exercise intensity from 25 to 65% maximal oxygen consumption
(O2 max) appears to
increase lipolysis in association with increasing plasma epinephrine
concentrations (33). This association suggests that the increases in
plasma epinephrine might be responsible for the increases in lipolysis
when exercise is increased from low to moderate intensities. However,
when exercise intensity increases from 65 to 85%
O2 max, lipolysis plateaus
despite further large increases in plasma epinephrine concentration
(33).
This last observation suggests that either 1) lipolysis is
maximally stimulated by the plasma epinephrine levels achieved at 65%
of O2 max or 2)
epinephrine stimulation of lipolysis is counteracted by increases in
exercise intensity that somehow suppress lipolysis. No study, to our
knowledge, has directly quantified lipolysis when increasing plasma
epinephrine levels during exercise. Furthermore, a possible interaction
between plasma epinephrine levels as a stimulator of lipolysis and
exercise intensity as an inhibitor of lipolysis has not been considered.
The main aim of the present study was to determine the effect of graded
elevations of plasma epinephrine concentration on lipolysis, the rate
of appearance (Ra) of free fatty acid (FFA), and fatty acid
oxidation during low-intensity exercise. The effect of increasing
plasma epinephrine levels on reesterification (i.e., nonoxidative
lipolysis) was also determined. To make these determinations, we
performed three intravenous epinephrine infusion trials at increasing
doses (low, moderate, and high) to raise plasma epinephrine concentrations progressively yet within physiological values observed during aerobic exercise at ~45, 65, and 85% of peak oxygen
consumption (O2 peak). The
exercise intensities used in this investigation (i.e., 25 and 45% of
O2 peak) correspond to
those which people typically choose when exercising for health and body
fat reduction.
Another aim of the present study was to separate the lipolytic effects of increasing plasma epinephrine from the lipolytic effects of increasing exercise intensity. The hypothesis tested was that increases in exercise intensity attenuate the lipolytic effects of raising plasma epinephrine concentrations.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Subjects.
Seven moderately trained men (n = 4) and women
(n = 3) participated in this experiment. Subjects were
healthy and were not taking any medication. The women were
premenopausal and were not taking oral contraceptives. In the women,
testing was performed in the follicular phase. The subject's mean age,
O2 peak, peak heart rate
while cycling, body weight, and percent body fat were 29 ± 7 yr, 52.2 ± 5 ml · kg
1 · min
1,
187 ± 10 beats/min, 68.6 ± 11 kg, and 15.9 ± 7%, respectively. Each of the seven subjects participated in five treatments. A subset
sample of five male subjects was recruited and participated in only two
treatments. These subjects were recruited to enlarge our sample and be
able to test differences that we found close to significance after
testing the seven original subjects. Their characteristics were similar
to the original subjects. Mean age,
O2 peak, peak heart rate
while cycling, body weight, and percent body fat were 27 ± 8 yr, 63.8 ± 8 ml · kg
1 · min
1,
189 ± 9 beats/min, 74.6 ± 10 kg, and 13.4 ± 4%, respectively. Before participation in the testing, subjects were informed of the
possible risks involved and signed a consent form approved by the
Internal Review Board of the University of Texas at Austin.
Preliminary testing, diet, and training.
O2 peak was determined
while subjects cycled an ergometer (model 819; Monark, Varberg, Sweden)
using an incremental protocol lasting 7-10 min. Two days before
the first experimental trial, subjects performed a standardized
training bout (40 min of cycling at 45%
O2 peak) to ensure
homogeneity of the last exercise bout. Subjects exactly replicated the
last meal before each test and restrained from training during the 24 h before the trials.
Experimental procedure. Subjects arrived at the laboratory in the morning, after an overnight fast (i.e., 12 h). Teflon catheters were inserted in an antecubital vein in each arm for infusion and blood sampling. A heating pad was affixed to the sampling forearm to obtain arterialized blood. After 60 min of resting isotope infusion (see below), subjects pedaled a cycle ergometer (Jaeger-Ergotest) for 60 min at either low or moderate intensity.
Epinephrine infusion.
Fifteen minutes into the exercise period, epinephrine (Adrenalin,
Chloride Solution; Parke-Davis) was infused at a constant rate until
the end of the exercise period at 60 min. Four of the experimental
trials only differed in the rate of epinephrine infusion: 0.005 µg · kg1 · min
1
(LOW), 0.015 µg · kg
1 · min
1
(MID), 0.045 µg · kg
1 · min
1
(HIGH), or no epinephrine infusion (CON 25%). These four trials were
performed at an intensity that elicited 25% of the subject
O2 peak. One additional
trial was performed at 45% of
O2 peak without
epinephrine infusion (CON 45%). During all five trials,
electrocardiogram tracing was monitored throughout the testing period
to confirm that normal sinus rhythm was maintained. Trials were
separated by at least 48 h, and the order of the trials was randomized.
Isotope infusion.
Upon catheterization, blood was sampled (4 ml) for determination of
background isotopic enrichment. Next, a primed constant-rate infusion
of [2H5]glycerol (prime = 3.7
µmol/kg; constant = 0.25
µmol · kg1 · min
1;
Isotec, Miamisburg, OH) and [1-13C]palmitate (Cambridge
Isotope Laboratories, Andover, MA) bound to 5% human albumin (0.04 µmol · kg
1 · min
1;
no prime) was started using calibrated syringe pumps (Harvard Apparatus, South Natick, MA). These stable isotope infusions were delivered during 60 min of rest to achieve isotopic equilibrium and
maintained at their constant rate throughout exercise. During the CON
45% trial, [2H5]glycerol was the only
stable isotope infused.
Blood sampling and analysis.
For determination of resting glycerol and palmitate kinetics, blood
samples were withdrawn 5 min before and immediately before exercise.
During exercise, blood samples (~14 ml) were collected every 10 min.
After collection, blood samples were divided into four different
prechilled tubes according to the constituents to be analyzed. For each
tube, plasma was separated by centrifugation (i.e., 3,000 rpm for 20 min at 4°C) and immediately frozen at 70°C until analysis. Four
milliliters of each blood sample were placed in tubes containing 0.2 ml
of EDTA (25 mg/ml) and were analyzed for isotopic enrichment of the
hepatofluorobutyric anhydride derivative of glycerol (13) and the
methyl ester derivative of palmitate (14) using gas chromatography-mass
spectrometry (Hewlett-Packard 5989). Five milliliters of plasma were
placed in tubes containing 0.25 ml of EDTA (25 mg/ml) for determination of plasma glycerol (fluorometric assay; see Ref. 9) and plasma FFA
(colorimetric assay; see Ref. 30). Three milliliters of blood were
mixed in a tube containing 0.3 ml of a solution of reduced gluthathione
(4.5 mg), sodium heparin (50 IU), and 20 µl of 0.24 M EGTA for
determination of epinephrine and norepinephrine concentration (HPLC
with electrochemical detection; see Ref. 16). The final 2 ml of each
blood sample were placed in a test tube containing 0.2 ml of an EDTA
(24 mg/ml)-aprotinin (0.5 tissue inhibitor units/ml) solution and were
analyzed for plasma insulin concentration (RIA; Linco Research, St.
Charles, MO).
Measurements of gas exchange. Periodically, during rest and exercise, subjects inhaled through a two-way Daniels valve while inspired air volume was measured with a Parkinson-Cowan CD4 dry gas meter (Rayfield Equipment, Waitsfield, VT). The expired gases were continuously sampled from a mixing chamber and were analyzed for oxygen (Applied Electrochemistry, SA3; Ametek, Pittsburgh, PA) and carbon dioxide (LB2; Beckman, Schiller Park, IL). These instruments were interfaced to a computer for calculation of the rate of oxygen consumption and rate of carbon dioxide production.
Calculations.
Plasma glycerol and palmitate kinetics were calculated using the
one-pool model non-steady-state equations of Steele (38) modified for
use with stable isotopes
![]() |
![]() |
![]() |
![]() |
![]() |
Statistical analysis. SPSS software was used for statistical analysis. Statistical differences among treatments and over time were identified using ANOVA with repeated measures in a complete within-subjects design. Time points were specifically examined for significance, using contrasts solved by univariate repeated measures. Statistical significance was defined as P < 0.05. The results are presented as means ± SE.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Plasma epinephrine, norepinephrine, and insulin
concentrations.
Plasma epinephrine concentrations gradually increased above CON
(0.59 ± 0.10 nM) with the LOW, MID, and HIGH rates of epinephrine infusion (0.96 ± 0.10, 1.92 ± 0.24, and 3.44 ± 0.50 nM,
respectively; all P < 0.05; Table
1). Exercise at 45%
O2 peak (CON 45%) increased
plasma epinephrine to levels similar to exercise at 25% of
O2 peak with a LOW rate of
epinephrine infusion (0.96 ± 0.1 nM). Plasma norepinephrine did not
increase above rest (1.4 ± 0.3 nM) during the 60 min of CON 25%
O2 peak exercise
(1.8 ± 0.3 nM). Intravenous epinephrine infusion (i.e., LOW, MID,
or HIGH) did not affect plasma norepinephrine concentration. However,
increases in exercise intensity during CON 45% increased norepinephrine levels (3.6 ± 0.9 nM at 60 min;
P < 0.05) above the trials performed at 25%
O2 peak.
|
Plasma glycerol and FFA kinetics during exercise at 25%
O2 peak.
Lipolysis (i.e., Ra glycerol) was stable during the
interval between 35 and 55 min of exercise in all trials (Fig.
1). The LOW
rate of epinephrine infusion significantly increased lipolysis above
CON (6.5 ± 0.5 vs. 4.9 ± 0.5
µmol · kg
1 · min
1,
respectively; P < 0.05). MID increased lipolysis modestly
above LOW (7.1 ± 0.8
µmol · kg
1 · min
1;
P < 0.05). HIGH overcame this apparent lipolytic plateau
and resulted in higher lipolysis than any other trial (10.6 ± 1.2 µmol · kg
1 · min
1;
all P < 0.05). Plasma glycerol concentration responded
similarly to Ra glycerol.
|
|
Fatty acid oxidation during exercise at 25%
O2 peak.
During the first 10 min of epinephrine infusion, fatty acid oxidation
declined below CON (9.9 ± 0.3
µmol · kg
1 · min
1)
gradually with LOW, MID, and HIGH (8.1 ± 0.6, 3.6 ± 0.9, and 1.5 ± 0.9
µmol · kg
1 · min
1,
respectively; P < 0.05; Fig.
3). During the interval between 35 and 55 min of exercise, fatty acid oxidation increased in all trials but
remained lower than CON (11.1 ± 0.8
µmol · kg
1 · min
1)
during MID and HIGH (8.7 ± 0.7 and 8.1 ± 0.9
µmol · kg
1 · min
1,
respectively; P < 0.05). In contrast, during LOW, fatty
acid oxidation returned to CON levels and even tended to increase above CON (11.7 ± 0.7
µmol · kg
1 · min
1,
n = 7; P < 0.08). When five additional subjects
were added to the original data set (i.e., n = 12), fatty
acid oxidation during LOW was significantly higher than during CON for
the last 30 min of exercise (12.9 ± 1.0 vs. 11.4 ± 1.0
µmol · kg
1 · min
1,
respectively, n = 12; P < 0.05).
|
Reesterification during exercise at 25%
O2 peak.
During the interval between the 35 and 55 min of exercise, total
reesterification of fatty acid (i.e., Ra glycerol × 3
fatty acid oxidation) increased progressively above CON (3.6 ± 0.2
µmol · kg
1 · min
1)
with the graded LOW, MID, and HIGH epinephrine infusions
(7.8 ± 0.6, 12.6 ± 0.7, and 23.7 ± 1.1
µmol · kg
1 · min
1,
respectively; P < 0.05; Fig.
4). During CON and LOW, calculated minimal
plasma FFA reesterification (i.e., Rd FFA
FFA
oxidation) was nearly zero since the rates of Rd FFA
matched total fatty acid oxidation rates. However, minimal plasma FFA
reesterification increased above CON during MID and HIGH (6.6 ± 0.5
and 12.9 ± 0.9
µmol · kg
1 · min
1,
respectively; P < 0.05).
|
Fat metabolism during exercise at 25 vs. 45%
O2 peak.
At a similar plasma epinephrine concentration, lipolysis was lower
during CON 45%
O2 peak than
during LOW 25%
O2 peak (5.5 ± 0.6 vs. 6.5 ± 0.5
µmol · kg
1 · min
1,
respectively; P < 0.05; Fig.
5). However, fatty acid oxidation was
higher during CON 45%
O2 peak, and thus
total reesterification was lower during CON 45%
O2 peak than during LOW 25%
O2 peak (i.e., 2.1 ± 0.1
vs. 7.8 ± 0.6
µmol · kg
1 · min
1,
respectively; P < 0.05; Fig.
6). Without epinephrine infusion, increases
in exercise intensity from 25 to 45% of
O2 peak increased lipolysis
and fatty acid oxidation similarly. As a consequence, total
reesterification remained similar during 25 and 45%
O2 peak exercise
(3.6 ± 0.2 vs. 2.1 ± 0.1
µmol · kg
1 · min
1,
respectively; Fig. 6). However, the excessive elevation of plasma epinephrine during LOW 25% resulted in a large increase in total reesterification due to the simultaneous increase in lipolysis and
reduction in fatty acid oxidation.
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The first major finding of the present experiment is that graded
epinephrine infusion progressively increased lipolysis (i.e., Ra glycerol) and the release of fatty acid into plasma
(i.e., Ra FFA) during low-intensity exercise (i.e., 25% of
O2 peak). Lipolysis
responded to small (i.e., LOW) and large (i.e., HIGH) elevations in
plasma epinephrine without an apparent plateau response (Fig. 4). In
contrast, when plasma epinephrine concentrations are elevated to levels
similar to HIGH (i.e., ~3 nM) by increasing exercise intensity (i.e.,
from 65 to 85%
O2 max),
lipolysis plateaus (33) and Ra FFA is reduced (22). This
led to the speculation that an increase in exercise intensity
attenuates epinephrine stimulation of lipolysis.
To directly test this hypothesis, lipolysis was presently compared
during exercise at 45% of
O2 peak with that at 25% of
O2 peak with epinephrine
infusion, so as to match plasma epinephrine levels (i.e., LOW; see
Fig. 5). The second major finding of the present study was
that at the same plasma epinephrine concentration (i.e.,
0.96 ± 0.10 nM), lipolysis was significantly lower at 45 than
at 25% of
O2 peak.
However, the mechanism by which increasing exercise
intensity reduces epinephrine stimulation of lipolysis is unclear.
Fatty acid oxidation declines when exercise intensity is increased from moderate to high levels (8, 20, 33, 37), and it would seem appropriate for the concomitant large increases in plasma epinephrine concentration to be somehow restrained from progressive stimulation of lipolysis. Otherwise, an excess of fatty acids would be made available during intense exercise, a condition that appears to actively limit fatty acid oxidation in association with a high glycolytic flux (7, 37). Fatty acids released in lipolysis can only be oxidized or reesterified. To prevent the accumulation of FFA in plasma and in the interstitial space, of which there is only a very limited storage capacity, it therefore seems possible for some factor associated with increasing exercise intensity to restrain epinephrine from excessive stimulation of lipolysis.
During CON 25%
O2 peak and during LOW, the
rates of plasma Rd FFA were equal to FFA oxidation. Because
these rates matched, it is possible that fatty acid oxidation was
supplied exclusively by plasma Rd FFA (37), and thus no
reesterification from plasma fatty acid took place during CON or LOW.
However, MID and HIGH increased plasma Rd FFA while
reducing fatty acid oxidation, which increased the calculated minimal
plasma fatty acid reesterification and total reesterification (Fig. 4).
In contrast, increases in epinephrine concentration by increasing exercise intensity (i.e., CON 25% and CON 45% of
O2 peak) stimulated
lipolysis simultaneously with fatty acid oxidation, and thus total
reesterification was maintained at low levels (Fig. 6).
Any amount of epinephrine infused that increased plasma epinephrine
concentration above normal control levels (i.e, LOW, MID, and HIGH)
increased total reesterification rates (Fig. 4). This implies that, in
these young, healthy, and moderately trained subjects, their normal
plasma epinephrine response to exercise is appropriate for matching
lipolysis to fatty acid oxidation, thus minimizing total
reesterification. An excessive epinephrine response during exercise at
25% O2 peak
clearly increased total and minimal plasma FFA reesterification (Fig.
4). Therefore, an excessive epinephrine response during low-intensity
exercise does not seem beneficial for stimulating fat oxidation and
increases the mobilization of fatty acid in plasma (i.e.,
Ra FFA), whose fate is reesterification rather than oxidation.
The increased plasma epinephrine concentration with increased exercise intensity serves numerous metabolic and cardiovascular functions (e.g., increased cardiac output and liver gluconeogenesis), and it certainly functions to stimulate lipolysis during exercise (2). The present results further indicate that epinephrine, per se, stimulates lipolysis during exercise to a level that is in excess of fatty acid oxidation. It appears, therefore, that some other factors associated with increased exercise intensity beneficially attenuate the epinephrine stimulation of lipolysis and thus minimize reesterification. Excessive lipolysis during exercise has been observed in the elderly and untrained population, who are also characterized as having elevated plasma catecholamine levels (27, 32). It is possible that the excessive lipolysis observed in these populations is originated by the overproduction of catecholamines. In addition, during aging and in obesity, the antilipolytic effect of insulin is reduced, which may also contribute to the unrestrained lipolysis (21, 23). It has been suggested that excessive lipolysis and reesterification may contribute to the high-risk blood lipid profile observed in patients with diabetes or obesity (5). Interventions that reduce the catecholamine response to exercise (i.e., aerobic training) have been shown to reduce reesterification (32, 36).
It is becoming evident that adipose tissue blood flow (ATBF) is
involved in the regulation of lipolysis (3). It has been shown that
vasoconstriction of adipose tissue is accompanied by a decreased rate
of lipolysis in adipocytes (1). In rats, increases in exercise
intensity to high levels result in a redistribution of blood flow away
from noncontracting muscle and adipose tissue (25). In humans,
increases in exercise intensity can reduce conductance to the skin
(39), the splanchnic area (34), and likely adipose tissue. Reductions
in ATBF could prevent epinephrine from stimulating lipolysis and might
possibly explain our observation that a given plasma epinephrine
concentration reduced whole body lipolysis as exercise intensity
increases from 25 to 45%
O2 peak. However,
it is unknown if the mild elevation in exercise intensity from 25 to
45% of
O2 peak would be
enough stimulus to reduce ATBF.
At rest, adipose tissue lipolysis is inhibited by -adrenergic
stimulation (2). Epinephrine and norepinephrine bind to
-adrenergic
receptors, which could reduce their own stimulatory effect on
lipolysis. Although epinephrine levels were similar during CON 45% and
LOW 25%
O2 peak,
norepinephrine levels were significantly elevated at the higher
exercise intensity (CON 45%, Table 1). The higher plasma
norepinephrine levels during CON 45%
O2 peak could have
counteracted epinephrine lipolytic effects. However, during
moderate-intensity exercise,
-adrenergic blockade does not appear to
affect lipolysis in subcutaneous adipose tissue (2). The role of
-adrenergic receptors in whole body lipolysis during exercise
remains unclear.
MID and HIGH epinephrine infusion elevated plasma insulin (i.e., 2.8 µU/ml, P < 0.05) above control levels (Table 1) in association with increases in plasma glucose levels (28). Lipolysis is very sensitive to increases in plasma insulin (4, 18), and reductions in lipolysis might occur with insulin elevation of only 2-3 µU/ml such as those observed during MID and HIGH. However, the elevation in plasma insulin levels during MID and HIGH did not prevent graded epinephrine infusion from progressively increasing lipolysis. Therefore, the potent antilipolytic effect of insulin in the present study was overpowered by the increase in plasma epinephrine concentration that apparently created the overall effect of progressively stimulating lipolysis. Nevertheless, the increasing levels of plasma insulin with the graded epinephrine infusion may have modulated the full effect of epinephrine-stimulated lipolysis.
Recent reports have suggested that Ra glycerol may underestimate whole body lipolysis due to utilization of glycerol within inactive muscle (19, 24). However, the low activity of glycerol kinase in mammalian skeletal muscle (29) makes large muscle glycerol utilization unlikely. During rest and low-intensity exercise, adipose tissue (rather than skeletal muscle) accounts for most of the lipolysis (24, 37). Although glycerol utilization by skeletal muscle is possible, glycerol utilization by adipose tissue it very unlikely. Human adipose tissue does not take up glycerol (6, 35), likely due to the low activity of glycerol kinase (26) and the inability of this tissue to utilize glycerol. It is unlikely that skeletal muscle glycerol utilization measurably affects plasma Ra glycerol during low-intensity exercise.
In the present experiment, the differences in Ra glycerol between trials were significant and large, occurred within a few minutes of epinephrine infusion, and were graded in accordance with the graded epinephrine infusion rates. Therefore, although Ra glycerol may not be an exact quantitative measure of whole body lipolysis, it appears to be sensitive to the increases in plasma epinephrine concentration. A possible error incurred by the use of Ra glycerol as a measurement of lipolysis should be similar in all trials, and thus the comparison among treatments and the conclusions derived should remain valid.
Elevations in lipolysis above CON levels by LOW rates of epinephrine infusion significantly increased fatty acid oxidation (i.e., 13%, n = 12; Fig. 3) in association with increased plasma FFA concentration. After 15 min of LOW, epinephrine stimulation of carbohydrate oxidation decreased, which likely allowed the available fatty acid to be oxidized. It has been reported that increases in glycolytic flux directly impair the oxidation of plasma FFA during exercise (7, 37). During moderate-intensity exercise, increases in plasma epinephrine concentrations to high but physiological levels increase muscle glycogen utilization (10) and thus glycolytic flux. Apparently, epinephrine infusions that stimulated carbohydrate oxidation (i.e., MID and HIGH) did not permit increases in fatty acid oxidation despite high plasma FFA availability. This suggests that, when plasma epinephrine stimulates both lipolysis and glycogenolysis, carbohydrate oxidation predominates over fatty acid oxidation that is reduced.
In summary, during low-intensity exercise (25%
O2 peak), graded
epinephrine infusion progressively stimulates lipolysis and plasma FFA
mobilization. However, increases in exercise intensity (i.e., from 25 to 45%
O2 peak) somehow
counteract epinephrine from stimulating lipolysis. This creates a
better match between lipolysis and fatty acid oxidation rates and thus
reduces total reesterification.
![]() |
ACKNOWLEDGEMENTS |
---|
We appreciate the technical support of Dr. Jeffrey Horowitz, Dr. Lauri O. Byerley, and Dr. Andrew Coggan and the medical assistance of Dr. Paul Roach. We also appreciate the assistance of Brad Hodgkinson, Matt Oseto, Melissa Domenick, Pamela Price, and the participants of this study.
![]() |
FOOTNOTES |
---|
This study was supported by a National Institute of Health Grant subcontract (from Dr. R. R. Wolfe to Dr. E. F. Coyle).
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. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: E. F. Coyle, The Univ. of Texas at Austin, Rm. 222, Bellmont Hall, Austin, TX 78712 (E-mail: coyle{at}mail.utexas.edu).
Received 8 June 1999; accepted in final form 4 November 1999.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Arner, P.
Regulation of lipolysis in fat cells.
Diabetes Rev
4:
450-463,
1996.
2.
Arner, P,
Kriegholm E,
Engfeldt P,
and
Bolinder J.
Adrenergic regulation of lipolysis in situ at rest and during exercise.
J Clin Invest
85:
893-898,
1990[ISI][Medline].
3.
Bulow, J,
and
Madsen J.
Influence of blood flow on fatty acid mobilization from lipolytically active adipose tissue.
Pfluegers Arch
390:
169-174,
1981[ISI][Medline].
4.
Campbell, PJ,
Carlson MG,
Hill JO,
and
Nurjhan N.
Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification.
Am J Physiol Endocrinol Metab
265:
E1063-E1069,
1992.
5.
Coppack, SW,
Jensen MD,
and
Miles JM.
In vivo regulation of lipolysis in humans.
J Lipid Res
35:
177-193,
1994[Abstract].
6.
Coppack, SW,
Persson M,
Judd RL,
and
Miles JM.
Glycerol and nonesterified fatty acid metabolism in human muscle and adipose tissue in vivo.
Am J Physiol Endocrinol Metab
276:
E233-E240,
1999
7.
Coyle, EF,
Jeukendrup AE,
Wagenmakers AJM,
and
Saris WHM
Fatty acid oxidation is directly regulated by carbohydrate metabolism during exercise.
Am J Physiol Endocrinol Metab
273:
E268-E275,
1997
8.
Edwards, HT,
Margaria R,
and
Dill DB.
Metabolic rate, blood sugar and the utilization of carbohydrate.
Am J Physiol
108:
203-209,
1934.
9.
Eggstein, M,
and
Kuhlmann E.
Triglycerides and glycerol. Determination after alkaline hydrolysis.
In: Methods of Enzymatic Analysis, edited by Bergmeyer HU.. New York: Academic, 1974, p. 1825-1831.
10.
Febbraio, MA,
Lambert DL,
Starkie RL,
Proietto J,
and
Hargreaves M.
Effect of epinephrine on muscle glycogenolysis during exercise in trained men.
J Appl Physiol
84:
465-470,
1988
11.
Friedlander, AL,
Casazza GC,
Horning MA,
Buddinger TF,
and
Brooks GA.
Effects of exercise intensity and training on lipid metabolism in young women.
Am J Physiol Endocrinol Metab
275:
E853-E863,
1998
12.
Galster, AD,
Clutter WE,
Cryer PE,
Collins JA,
and
Bier DM.
Epinephrine plasma thresholds for lipolytic effects in man.
J Clin Invest
67:
1729-1738,
1981[ISI][Medline].
13.
Gilker, CD,
Pesola GR,
and
Matthews DE.
A mass spectrometric method for measuring glycerol levels and enrichments in plasma using 13C and 2H stable isotopic tracers.
Anal Biochem
205:
172-178,
1992[ISI][Medline].
14.
Hachey, DL,
Patterson BW,
Reeds PJ,
and
Elsas LJ.
Isotopic determination of organic keto acid pentafluorobenzyl esters in biological fluids by negative chemical ionization gas chromatography/mass spectrometry.
Anal Chem
63:
919-923,
1991[ISI][Medline].
15.
Hirsch, IB,
Marker JC,
Smith LJ,
Spina RJ,
Parvin CA,
Holloszy JO,
and
Cryer PE.
Insulin and glucagon in prevention of hypoglycemia during exercise in humans.
Am J Physiol Endocrinol Metab
260:
E695-E704,
1991
16.
Hjemdahl, P.
Catecholamine measurements by high-performance liquid chromatography.
Am J Physiol Endocrinol Metab
247:
E13-E20,
1984
17.
Horowitz, JF,
Braudy RJ,
Martin WH, III,
and
Klein S.
Endurance exercise training does not alter lipolytic or adipose tissue blood flow sensitivity to epinephrine.
Am J Physiol Endocrinol Metab
277:
E325-E331,
1999
18.
Horowitz, JF,
Mora-Rodriguez R,
Byerley LO,
and
Coyle EF.
Lipolytic suppression following carbohydrate ingestion limits fat oxidation during exercise.
Am J Physiol Endocrinol Metab
273:
E768-E775,
1997
19.
Jensen, MD.
Regional glycerol and free fatty acid metabolism before and after meal ingestion.
Am J Physiol Endocrinol Metab
276:
E863-869,
1999
20.
Jensen, MD,
Cryer PE,
Johnson CM,
and
Murray MJ.
Effects of epinephrine on regional free fatty acid and energy metabolism in men and women.
Am J Physiol Endocrinol Metab
270:
E259-E264,
1996
21.
Jensen, MD,
Haymond MW,
Rizza RA,
Cryer PE,
and
Miles JM.
Influence of body fat distribution on free fatty acid metabolism in obesity.
J Clin Invest
83:
1168-1173,
1989[ISI][Medline].
22.
Jones, NL,
Heigenhauser GJF,
Kuksis A,
Matsos CG,
Sutton JR,
and
Toews CJ.
Fat metabolism in heavy exercise.
Clin Sci
59:
469-478,
1980[ISI][Medline].
23.
Klein, S,
Young VR,
Blackburn GL,
Bistrian BR,
and
Wolfe RR.
Palmitate and glycerol kinetics during brief starvation in normal weight young adult and elderly subjects.
J Clin Invest
78:
928-933,
1986[ISI][Medline].
24.
Landau, BR,
Wahren J,
Previs SF,
Ekberg K,
Chandramouli V,
and
Brunengraber H.
Glycerol production and utilization in humans: sites and quatitation.
Am J Physiol Endocrinol Metab
271:
E1110-E1117,
1996
25.
Laughlin, MH,
and
Armstrong RB.
Muscular blood flow distribution patterns as a function of running speed in rats.
Am J Physiol Heart Circ Physiol
243:
H296-H306,
1982
26.
Margolis, S,
and
Vaughn M.
-Glycerophosphate synthesis and breakdown in homogenates of adipose tissue.
J Biol Chem
257:
44-50,
1962.
27.
Marker, JC,
Clutter WE,
and
Cryer PE.
Reduced epinephrine clearance and glycemic sensitivity to epinephrine in older individuals.
Am J Physiol Endocrinol Metab
275:
E770-E776,
1998
28.
Mora-Rodriguez, R,
Gonzalez-Alonso J,
Below PR,
and
Coyle EF.
Plasma catecholamines and hyperglycemia influence thermoregulation in man during prolonged exercise in the heat.
J Physiol Lond
491:
529-540,
1996[Abstract].
29.
Newsholme, EA,
and
Taylor K.
Glycerol kinase activity in muscles from vertebrates and invertebrates.
Biochem J
112:
465-474,
1969[ISI][Medline].
30.
Novak, M.
Colorimetric ultramicro method for determination of free fatty acids.
J Lipid Res
6:
431-433,
1965
31.
Peronnet, F,
and
Massicotte D.
Table of nonprotein respiratory quotient: an update.
Can J Sport Sci
16:
23-29,
1991[ISI][Medline].
32.
Phillips, SM,
Green HJ,
Tarnopolsky MA,
Heigenhauser GJF,
Hill RE,
and
Grant SM.
Effects of training duration on substrate turnover and oxidation during exercise.
J Appl Physiol
81:
2182-2191,
1996
33.
Romijn, JA,
Coyle EF,
Sidossis LS,
Gastadelli A,
Horowitz JF,
Endert E,
and
Wolfe RR.
Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.
Am J Physiol Endocrinol Metab
265:
E380-E391,
1993
34.
Rowell, LB.
Control of individual vascular beds: splanchnic and renal.
In: Human Circulation: Regulation During Physical Stress. New York: Oxford Univ Press, 1986, chapt. 5, p. 96-116.
35.
Samra, JS,
Simpson EJ,
Clark ML,
Forster CD,
Humphreys SM,
Macdonald IA,
and
Frayn KN.
Effects of epinephrine infusion on adipose tissue: interactions between blood flow and lipid metabolism.
Am J Physiol Endocrinol Metab
271:
E834-E839,
1996
36.
Sial, S,
Coggan AR,
Hickner RC,
and
Klein S.
Training-induced alterations in fat and carbohydrate metabolism during exercise in elderly subjects.
Am J Physiol Endocrinol Metab
274:
E785-E790,
1998
37.
Sidossis, LS,
Gastadelli A,
Klein S,
and
Wolfe RR.
Regulation of plasma fatty acid oxidation during low-and-high intensity exercise.
Am J Physiol Endocrinol Metab
272:
E1065-E1070,
1997
38.
Steele, R.
Influences of glucose loading and injected insulin on hepatic glucose output.
Ann NY Acad Sci
82:
420-430,
1959[ISI].
39.
Taylor, WF,
Johnson JM,
and
Kosiba WA.
Roles of absolute and relative load in skin vasoconstrictor responses to exercise.
J Appl Physiol
69:
1131-1136,
1990
40.
Wolfe, RR,
Peters EJ,
Klein S,
Holland OB,
Rosenblatt J,
and
Gary H.
Effect of short-term fasting on lipolytic responsiveness in normal and obese humans.
Am J Physiol Endocrinol Metab
252:
E189-E196,
1987