Substrate metabolism during different exercise intensities in endurance- trained women

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DOI: 10.1152/jappl.2000.88.5.1707 · Source: PubMed
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Abstract
We have studied eight endurance-trained women at rest and during exercise at 25, 65, and 85% of maximal oxygen uptake. The rate of appearance (R(a)) of free fatty acids (FFA) was determined by infusion of [(2)H(2)]palmitate, and fat oxidation rates were determined by indirect calorimetry. Glucose kinetics were assessed with [6,6-(2)H(2)]glucose. Glucose R(a) increased in relation to exercise intensity. In contrast, whereas FFA R(a) was significantly increased to the same extent in low- and moderate-intensity exercise, during high-intensity exercise, FFA R(a) was reduced compared with the other exercise values. Carbohydrate oxidation increased progressively with exercise intensity, whereas the highest rate of fat oxidation was during exercise at 65% of maximal oxygen uptake. After correction for differences in lean body mass, there were no differences between these results and previously reported data in endurance-trained men studied under the same conditions, except for slight differences in glucose metabolism during low-intensity exercise (Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E, and Wolfe RR. Am J Physiol Endocrinol Metab 265: E380-E391, 1993). We conclude that the patterns of changes in substrate kinetics during moderate- and high-intensity exercise are similar in trained men and women.
Substrate metabolism during different exercise
intensities in endurance-trained women
J. A. ROMIJN,
1
E. F. COYLE,
2
L. S. SIDOSSIS,
3,4
J. ROSENBLATT,
3,4
AND R. R. WOLFE
3,4
1
Department of Endocrinology and Metabolism, Leiden University Medical Center,
2300 RC Leiden, The Netherlands;
2
Human Performance Laboratory,
Department of Kinesiology and Health, The University of Texas at Austin, Austin 78712;
3
Metabolism Unit, Shriners Burns Institute, and
4
Departments of Anesthesiology
and Surgery, University of Texas Medical Branch, Galveston, Texas 77550
Romijn, J.A., E. F. Coyle, L. S. Sidossis, J. Rosenblatt,
and R. R. Wolfe. Substrate metabolism during different
exercise intensities in endurance-trained women. J Appl
Physiol 88: 17071714, 2000.—We have studied eight endur-
ance-trained womenatrestand during exercise at25,65,and
85%ofmaximal oxygenuptake.The rateof appearance(R
a
)of
free fatty acids (FFA) was determined by infusion of
[
2
H
2
]palmitate, and fat oxidation rates were determined by
indirect calorimetry. Glucose kinetics were assessed with
[6,6-
2
H
2
]glucose. Glucose R
a
increased in relation to exercise
intensity. In contrast, whereas FFA R
a
was significantly
increased to the same extent in low- and moderate-intensity
exercise, during high-intensity exercise, FFA R
a
was reduced
comparedwiththeotherexercisevalues.Carbohydrateoxida-
tion increased progressively with exercise intensity, whereas
the highest rate of fat oxidation was during exercise at 65% of
maximal oxygen uptake. After correction for differences in
lean body mass, there were no differences between these
results and previously reported data in endurance-trained
men studied under the same conditions, except for slight
differences in glucose metabolism during low-intensity exer-
cise (Romijn JA, Coyle EF, Sidossis LS, GastaldelliA, Horow-
itz JF, Endert E, and Wolfe RR. Am J Physiol Endocrinol
Metab 265: E380E391, 1993).We conclude that the patterns
of changes in substrate kinetics during moderate- and high-
intensity exercise are similarin trained men and women.
stable isotopes; body composition; glucose; glycogen; fatty
acids
THERE IS A COMMON PERCEPTION that women may be
relatively more suited to endurance exercise than men
because of a greater ability to use fatty acids as energy
substrates during exercise. This notion is supported by
several studies that have found some index of fat
metabolism to be greater in women than in men at
comparable exercise intensity (e.g., Refs. 7, 22). On the
other hand, several other studies have failed to show a
gender difference in substrate metabolism (3, 23). It
has been suggested that the difference in substrate
metabolism between men and women during exercise
becomes less as training status increases (19), but all
data are not consistent with this explanation. For
example, endurance-trained women were found to de-
rive more energy from lipids than endurance-trained
men did when exercising at 65% of maximal oxygen
consumption (V
˙
O
2max
) (21).
If women are in fact better able to rely on fat during
exercise than men, it may be because women generally
have a higher percentage of body fat than men. This
could theoretically lead to greater availability of fatty
acids during exercise and, inturn, to more fat oxidation
at a given exercise intensity than in a man with less
body fat. In this regard, changes in fatty acid availabil-
ity have been shown to have an effect on fatty acid
oxidation during high-intensity exercise (16). On the
other hand, it may be erroneous to assume that women
have an increased rate of lipolysis because of their
greater amount of body fat. Our laboratory has previ-
ously shown that changes in the percentbody fat result
in altered lipolytic sensitivity that makes individuals
with low body fat better able to mobilize fatty acids
than might be anticipated otherwise. Thus lipolytic
responsiveness is enhanced in subjects with low body
fat (11) and decreased inobese subjects (29).Consistent
with these observations, our laboratory found that
highly trained athletes had higher rates of lipolysis at
rest (18) than untrained controls did. However, it is not
clear whether this reflects a response to training, a
change in body composition, or some other factor. In
trained men, it is difficult to distinguish a training
effect on fat metabolism from a body-composition effect
because body fat is low in all endurance-trained men.
This is not necessarily the case in endurance-trained
women, who may have a relatively large range in body
composition. The purpose of the present study was
therefore twofold: 1) to compare with the previously
reported data from endurance-trained men (15) the
response of glucose and lipid kinetics in endurance-
trained women to three intensities of exercise and 2)to
evaluate the role of bodycomposition on the response of
substrate kinetics to exercise in the trained women. To
accomplish these goals, we have quantified glucose and
fatty acid kinetics by using stable isotopically labeled
tracers at three intensities of exercise in eight endur-
ance-trained women with a range in body composition
from 7.7 to 26.9% body fat.
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J Appl Physiol
88: 1707–1714, 2000.
8750-7587/00 $5.00 Copyright
r
2000 the American Physiological Society 1707http://www.jap.org
METHODS
Subjects
We studied eight well-trained female cyclists with percent
body fat ranging from 7.7 to 26.9%. Their physical character-
istics are shown in Table 1. All subjects were healthy, as
indicated by medical history and physical examination. They
were consuming a weight-maintaining diet containing at least
300–400 g of carbohydrates daily. They were in energy balance,
documented by their stable weight in the 2 mo preceding the
study. They were studied in the postabsorptive state after a
10- to 12-h fast and did not exercise the day before the
studies.Thesubjects wereeumenorrheicand studied through
a variety of phases of the menstrual cycle. The men we used
for comparison were describedpreviously (15).
Body composition was determined by densitometry by
using the hydrostatic weighing technique with correction for
residual lung volume (25). Relative body fat was estimated
from total body density (26). Assessment of body composition
was performed within 1wk of the isotope-infusion protocol.
V
˙
O
2max
had been determined several weeks before the
present protocol while the subjects cycled on a stationary
ergometer (model 819, Monark). V
˙
O
2max
was determined
during an incremental cycling protocol lasting 710 min. The
study was approved by the institutional review boards of the
University of Texas, Galveston andAustin.
Exercise Protocol
The subjects were studied on 2 consecutive days in the
postabsorptive state. On one occasion, the protocol consisted
of at least 120 min of bed rest, 60 min of exercise at 25% of
V
˙
O
2max
on a stationary ergometer (model 819, Monark),
followed by 60 min of bed rest, and, finally, 30 min of exer-
cise at 85% of V
˙
O
2max
. We have previously shown that the
effects of very-low-intensity exercise (120 min at 25% of
V
˙
O
2max
) on glucose and fat metabolism subside within1hof
bed rest (15). On the other day, the protocol consisted of at
least 120minof bed rest followedby60min of exercise at65%
of V
˙
O
2max
. The order of the two protocols was determined by
random allocation.
Indirect Calorimetry
Indirect calorimetry was performed at rest for at least 15
min continuously during the first 30 min of exercise (all 3
levels of exercise) and for 510 min at 15-min intervals
throughout the remainder of the exercise periods at 25 and
65% of V
˙
O
2max
. The values obtained from 20 to 30 min of
exercise were used to calculate and compare substrate oxida-
tion rates among the three levels of exercise. Our laboratory
(14) has previously shown that indirect calorimetry is a valid
method to measure substrate oxidation rates in trained
subjects during cycling exercise at 8085% of V
˙
O
2max
because
ofthe relativephysiological state(i.e., constantlactate concen-
tration, heart rate, and so forth) over this time interval. The
restingvalueswere obtained afterthesubjects hadbeenlying
on a bed for at least 1 h. Inspired volumes of air were
measured with a dry-gas meter (model CD-4, Parkinson-
Cowan). Aliquots of expired gas were sampled from a mixing
chamber for O
2
(model S3A, Applied Electrochemistry) and
CO
2
(model LB-2, Beckman). Analog outputs from the gas
analyses and gas meter were directed to a laboratory com-
puter for calculation of oxygen uptake and carbon dioxide
production.
Isotope Infusion
Teflon catheters were placed percutaneously in an antecu-
bital vein, and a sampling catheter was inserted in a dorsal
hand vein of the contralateral side. The heated hand tech-
nique was used to obtain arterialized blood samples. The
subjects lay on a bed for 1 h after catheter placement. Then,
after a blood sample was drawn to determine background
enrichment, primed, constant infusions of [6,6-
2
H
2
]glucose
(99% enriched, Merck, Rahway, NJ; 0.22 µmol·kg
21
·min
21
;
priming dose 17.6 µmol/kg) and [
2
H
2
]palmitate (0.04 µmol·
kg
21
·min
21
; no priming dose) were started by using cali-
brated syringe pumps (HarvardApparatus, Natick,MA). The
exact infusion rates in each experiment were determined by
measuring the concentrations in the infusates. The palmitate
tracer (99% enriched) was purchased from Tracer Technolo-
gies (Newton, MA). Palmitate was bound to albumin (Cutter
Biological, Berkeley, CA) by following previously described
procedures (27). After2hofinfusion at rest, exercise was
started and the rate of isotope administration was doubled
for palmitate (25 and 65% of V
˙
O
2max
) and glucose (65% of
V
˙
O
2max
) and tripled for glucose (85% of V
˙
O
2max
) to minimize
changes in substrate isotopic enrichment. These changes in
isotope infusion rates were determined from results of a
previousstudyon metaboliceffectsof similarexerciseintensi-
tiesinmen (15).Duringthe intervalbetween theexperiments
with exercise at 25 and 85%, the isotope infusions were
continued at the basalrates.
Blood Sampling
The first blood samples were drawn before the isotope
infusion was started to determine background enrichment.
Blood was also taken 110, 115, and 120 min after the
beginning of infusion to measure resting kinetics. During
high-intensity exercise, blood was drawn after 5, 10, 15, 20,
25, and 30 min of exercise. In moderate- and low-intensity
exercise, samples were drawn every 10 min for 60 min. All
samples were collected in 10-ml vacutainers containing
lithium heparin and were placed on ice. Plasma was sepa-
rated by centrifugation within 5 min of sampling and subse-
quently frozen until furtherprocessing.
Sample Analysis
Plasma glucose concentration was measured on a glucose
analyzer (Beckman Instruments) by use of the glucose oxi-
dase method. The enrichment of [6,6-
2
H
2
]glucose in plasma
was determined as previously described (27). Briefly, plasma
was deproteinated with barium hydroxide and zinc sulfate
solutions. Glucose was extracted by mixed-bed anion-cation
exchange chromatography (AG-1-X8 and AG 5OW-X8, Bio-
Rad Laboratories, Richmond, CA) and reacted with acetic
anhydride and pyridine to form the pentaacetate derivative.
Isotopic enrichment was determined by using gas chromato-
Table 1. Physical characteristics of study subjects
Subject
No.
Age,
yr
Weight,
kg
Height,
m
Weight,
kg
Fat,
%body
weight
V
˙
O
2max
,
l/min
1 31 48 1.65 44 7.7 2.75
2 27 49 1.63 42 13.4 2.75
3 29 55 1.60 47 14.8 3.30
4 26 63 1.66 52 17.8 3.60
5 28 64 1.65 53 18.4 3.83
6 25 69 1.78 55 20.5 3.90
7 29 65 1.65 51 21.6 4.15
8 18 72 1.77 53 26.9 3.65
Mean6SE 276 16163 1.6760.02 5062 17.662 3.496 0.2
V
˙
O
2max
, maximal oxygen uptake.
1708 SUBSTRATE METABOLISM IN EXERCISING WOMEN
graph-mass spectrometry (model 5985B, Hewlett-Packard,
Fullerton, CA) with electronic-impact ionization, selectively
monitoring ions at mass-to-charge ratio (m/z) 202, 201, and
200. Correction was made for the contribution of singly
labeled molecules (m/z 201) to the apparent enrichment at
m/z 202 (27).
FFA were extracted from plasma, isolated by thin-layer
chromatography, and derivatized to their methyl esters.
Palmitate and total free fatty acid (FFA) concentrations were
determined by gas chromatography (model 5890, Hewlett-
Packard)byusing heptadecanoicacidas an internalstandard
(27). Isotopic enrichment of palmitate was measured by gas
chromatograph-mass spectrometry analysis of the methyl
ester derivatives (model 5992, Hewlett-Packard). Ions of m/z
270 and 272 wereselectively monitored.
Calculations
Indirect calorimetry. Carbohydrate and fat oxidation rates
were calculated by using stoichiometric equations (4). Nitro-
gen excretion rate was assumed to be 135 µg·kg
21
·min
21
.
This average value was taken from the measured values
determined in another study performed in our laboratory (1).
A 30% error in this assumed value (which exceeds the total
range of values in the previous study) would have no signifi-
cant effect on the calculated values of fat and carbohydrate
oxidation in exercise in the present study. Fatty acid oxida-
tion was determined by converting the rate of triglyceride
oxidation (g·kg
21
·min
21
) to its molar equivalent, assuming
the average molecular mass of triglyceride is 860 g/mol (4)
and multiplying the molar rate of triglyceride oxidation by
three because each moleculecontains 3 mol of fatty acids.
Rates of appearance. Rate of appearance (R
a
) and, when
appropriate, rate of disappearance (R
d
5 tissue uptake) of
glucose and palmitate at rest were calculated by using the
equation of Steele (20), as modified for use with stable
isotopes (27). During exercise and the first 30 min ofrecovery,
the non-steady-state approximation of Steele was used in
conjunction with a spline-fitting program to smooth the raw
data(24).The effectivevolume of distributionwasassumed to
be165ml/kg forglucose and40ml/kg forpalmitate. Thevalue
for palmitate was chosen because acute changes in palmitate
concentration are essentially restricted to plasma (because
FFA are bound to albumin). The FFA R
a
was calculated by
dividing the palmitate R
a
by the fractional contribution of
palmitate to the total FFA concentration, as determined by
gas chromatography.
Statistical Analysis
The results obtained during 2030 min of exercise were
used for comparison of the subjects of the three levels of
exercise. The effect of time on the response within each
exercise level was analyzed by two-way analysis of variance
for a randomized block, with the subjects as blocks and time
as treatment. If necessary, the time effects were compared by
Fisher’s least significant difference test. The results of the
three exercise intensifies were compared by two-way analysis
ofvarianceforrandomized block design,inwhich the subjects
are blocks and the three exercise levels are treatments. If
necessary, the analysis of variance wasfollowedbyamultiple
comparison to detect differencesamong groups.
To analyze the effects of body composition and gender on
different metabolic responses (e.g., glucose production) we
used the repeated-measures analysis of covariance. Letting
Y
s,ef
denote the measured metabolic response from subject(s)
[person(s)] exercising at intensity level e, with body composi-
tion parameter f, the model is Y
s,ef
5 S
s
1 E
e
1 f(FE)
e
1
error
s,ef
, in which the error terms are assumed to be indepen-
dent, identically distributed, normal random variables with
mean value 0 and common SD
e
. The body composition factor
was either fat mass (FM), fat free mass (FFM), or the ratio
FM/FFM. Thus the repeated-measures aspect is included via
the subject effect S
s
, and the effect of body composition is
accounted for by the f(FE) term. To ensure unique estimates,
the baseline constraints E
1
5 0 and (FE)
1
5 0 were imposed.
In this case, E
e
and (FE)
e
represent the rise over baseline
levels of intercept and slope, respectively. The effect of body
composition at baseline, along with any other baseline vari-
abilityassociatedwithbodycompositionorotherfixedcharac-
teristics of subjects, is embodied in the S
s
. If the body
composition were the only such factor, the values of the S
s
would specify the average effect of body composition on the
baseline metabolic response. Simultaneously, 0.95level confi-
dence intervals for the parameters E
e
and (FE)
e
were gener-
ated in association with a repeated-measures analysis of
covariance F-test of the hypothesis H
o
:E
e
5 0, (FE)
e
5 0, e 5
2,3,4. Data fromaprevious paper (15)fromour laboratory, in
which the exact same experimental procedures were used in
trained male subjects, were used for evaluation of gender
effect.
RESULTS
Resting State
At rest, there were no differences in concentrations,
R
a
, or oxidation rates of FFAor glucose before the three
levels of exercise. Themeanvalues are showninTable 2.
Exercise
Lactate concentrations. Lactateconcentrationdid not
change during low-intensity exercise and increased
from 0.84 6 0.03 to 1.68 6 0.18 mmol/l (P , 0.05)
during moderate exercise intensity. During high-
intensityexercise,lactateconcentrationswereconsider-
ablyhigher,but,nonetheless,physiologicalsteadystate
was maintained. This was reflected in plasma lactate
concentrations over the last 15 min of exercise (0 min:
0.84 6 0.03, 15 min: 7.92 6 0.17, 30 min: 7.30 6 0.71
mmol/l).
Glucose metabolism. Tracer-to-tracee ratios and sub-
strate kinetics are shown in Figs. 1 and 2, respectively.
During low-intensity exercise, plasma glucose concen-
tration and glucose R
a
did not change from the resting
values. In contrast, during moderate- and high-intensity
exercise, plasma glucose concentration and glucose R
a
increased significantly in relation to exercise intensity
(Tables 2 and 3).
FFAmetabolism.FFAconcentrationsincreasedgradu-
ally during low-intensity exercise, whereas they tran-
siently decreased and subsequently increased during
moderate exercise intensity [not significant (NS) vs.
low-intensity exercise]. During high-intensity exercise,
FFA concentrations were considerably decreased com-
pared with the values obtained at rest and during
low-intensity exercise (P, 0.05; Table 3). Palmitate R
a
,
FFAR
a
, and FFAuptake were significantly increased to
the same extent in low- and moderate-intensity exer-
cise(Fig.2,Tables2and3).Duringhigh-intensityexercise,
palmitate R
a
,FFAR
a
and FFA uptake were significantly
1709
SUBSTRATE METABOLISM IN EXERCISING WOMEN
lower than the values during the two lower exercise
intensities (P, 0.05; Fig. 2, Tables 2 and 3).
Substrate oxidation rates. Substrate oxidation rates
are given in Tables 2 and 3. During moderate-intensity
exercise, carbohydrate oxidation rates increased above
the value during low-intensity exercise, and carbohy-
drate oxidation was the highest during high-intensity
exercise. The highest rate of fat oxidation was during
exercise at 65% of V
˙
O
2max
(Table 3), whereas there was
no significant difference between low- and high-intensity
exercise.
During exercise at 25% of V
˙
O
2max
, FFA uptake and
FFA oxidation rates, expressed in fatty acid equiva-
lents, were similar (Table 2), indicating that plasma
could transport adequate amounts of FFAfor oxidation
from adipose tissue. However, during moderate and
high exercise intensity, fatoxidation ratesexceeded the
maximal amounts that could be obtained from plasma,
the differencebeing the minimal contribution of muscle
triglycerides toenergy requirements (Fig. 3). From Fig.
3,itisalsoevident thatthemaximalcombinedcontribu-
tion of plasma glucose and FFA to oxidation rates
hardly differs between the three levels of exercise.
Apparently, the decrease in FFA R
d
during high-
intensity exercise more or less balances the increase in
glucose R
d
.
Relationship of Results to Gender
Table 2 shows the comparison between the women
and the previously described men. V
˙
O
2max
, expressed
per kilogram of lean body mass, was similar in both
groups. In addition, respiratory exhange ratio (RER)
values obtained during different exercise intensifies
were not different. Despite decreased glucose R
d
and
increased rate of carbohydrate oxidation during low-
intensity exercise in the women, there were no differ-
ences in glucose and fat metabolism between men and
women after correction for differences in lean body
mass. The minimal contribution of muscle triglycerides
to energy requirements were 0 vs. 9% (men vs. women)
at 25% of V
˙
O
2max
(P , 0.05), 23 vs. 25% at 65% ofV
˙
O
2max
(NS) and 11 vs. 17% at 85% of V
˙
O
2max
(NS). Muscle
glycogen contributed minimally, 0 vs. 9% (men vs.
women) at 25% of V
˙
O
2max
(P , 0.05), 41 vs. 34% at 65%
of V
˙
O
2max
(NS), and 63 vs. 58% at 85% of V
˙
O
2max
(NS).
DISCUSSION
The results of this study indicate that substrate
metabolisminendurance-trainedwomen respondssimi-
larly to moderate- and high-intensity exercise, as our
laboratory has previously reported in endurance-
trained men (15). A greater relative amount of body fat
in women is a potential basis for expecting a difference
in substrate metabolism between trained men and
women. In this study, we were able to assess the effect
ofbodycompositionon substratemetabolismbycompar-
ing men and women with comparable training status
but with different body composition. Because we found
no metabolic effect of gender, substrate metabolism
during exercise is determined by energy requirements
of lean body mass, rather than by gender or body
composition.
Therewas a slight differenceinstudydesignbetween
the present study and the previous study in men (15).
In the present study in women, exercise at 85% of
V
˙
O
2max
was performed on the same day as the exercise
study at 25% V
˙
O
2max
. The two exercise studies were
separated by an interval of 1 h. In the study in men, we
performed the three exercise protocols on 3 separate
days. One might argue that this difference in design
affects our conclusion as to the comparison of the
results at 85% of V
˙
O
2max
. However, there was no gender
effect after correction for differences in lean body mass.
Moreover, in the study in men, we documented that all
changes induced by exercise at 25% of V
˙
O
2max
subsided
within the first hour of recovery. Finally, exercise at
25% of V
˙
O
2max
in trained subjects only involves cycling
withoutanyresistance. This very low exerciseintensity
is not reflected in any change in glucose R
a
. Therefore,
Table 2. Comparison of anthropometric values and
substrate metabolism at rest and after 2030 min of
exercise at different exercise intensities in
endurance-trained men and women
Men
(n5 5)
Women
(n5 8)
P
Value
Weight 75.263.6 60.663.2 ,0.02
Height 1.7860.03 1.6760.02 ,0.05
Lean body mass 68.263.3 49.561.6 ,0.01
Fat mass 8.160.2 11.16 1.7 NS
V
˙
O
2max
l/min 5.0160.3 3.560.2 ,0.05
ml/kg lean body mass 73.66 3.5 70.16 2.0 NS
RER
Rest 0.7860.01 0.7660.01 NS
25% 0.7360.01 0.7560.01 NS
65% 0.8160.02 0.8160.01 NS
85% 0.9160.01 0.9060.01 NS
FFAuptake, µmol·kg lean
body mass
21
·min
21
Rest 17.061.4 15.961.9 NS
25% 29.062.9 26.661.6 NS
65% 25.262.5 29.463.0 NS
85% 19.063.7 15.661.5 NS
Fatty acid oxidation,
µmol·kg lean body
mass
21
·min
21
Rest 6.760.5 5.860.5 NS
25% 26.161.6 30.161.7 NS
65% 47.064.6 53.363.5 NS
85% 33.465.0 36.863.9 NS
R
d
glucose, µmol·kg lean
body mass
21
·min
21
Rest 11.56 0.4 11.66 0.4 NS
25% 14.360.4 11.26 0.6 ,0.01
65% 24.561.2 28.562.7 NS
85% 56.962.1 51.7611.7 NS
Carbohydrate oxidation,
µmol·kg lean body
mass
21
·min
21
Rest 6.460.9 6.261.2 NS
25% 11.56 3.4 22.26 3.7 ,0.01
65% 150.9630.0 130.7612.7 NS
85% 331.1617.5 285615.5 NS
Values are means 6 SE; n, no. of subjects. RER, respiratory
exchange ratio; FFA, free fatty acid; R
d
, rate of disappearance; NS,
not significant.
1710 SUBSTRATE METABOLISM IN EXERCISING WOMEN
it seems unlikely that the slight differences in study
design between the two studies affect our conclusion to
a considerable extent.
Several other studies have evaluated the changes in
substrate metabolism in relation to exercise intensity.
Our data extend the observations of Friedlander et al.
(5), which involved the effects of exercise at 52 and
65% of V
˙
O
2max
in women after 812 wk of endurance
training. They observed that there was no significant
difference in FFAR
a
between these exercise intensities,
in line with our observation that FFAR
a
is not different
even between 25 and 65% of V
˙
O
2max
in trained women.
Fig. 1. Tracer-to-tracee ratios of palmitate (A) and glucose
(B) at rest and during exercise at 25, 65, and 85% of
maximal oxygen uptake. Values are means 6 SE for 8
women.
Fig. 2. Rates of appearance (R
a
) ofpalmitate (A)and
glucose (B) at rest and during exercise at 25, 65, and
85% of maximal oxygen uptake. Values are means 6
SE for 8 women.
1711SUBSTRATE METABOLISM IN EXERCISING WOMEN
  • Article
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    Objectives: The present study verified the effect of moderate to high intensity aerobic exercise on the endocrine response profile and adipose tissue in young healthy men with different phenotype characteristics. Design: Eighteen men were divided into three experimental groups with defined body components and specific physical fitness: Endurance phenotype - EP (n=6; low body mass; low fat content; aerobic endurance trained), Athletic phenotype - AP (n=6; high body mass; low fat content, resistance trained), Obesity phenotype - OP (n=6; high body mass; high fat content, untrained). Methods: The participants performed an progressive exercise protocol on a treadmill (30% VO2max, 50% VO2max, 70% VO2max), separated by 45s of passive rest for blood collection. Results: Plasma glucose oxidation increased in relation to exercise intensity, but to a greater extent in the AP group. The free fatty acids plasma level decreased with a rise in exercise intensity, but with different kinetics in particular phenotypes. Plasma growth hormone increased after the cessation of exercise, and was significantly higher in all groups 45 minutes into recovery compared to resting values. Plasma insulin decreased during exercise in all groups, but in the OP, the decrease was blunted. Conclusions: The results indicate that the rate of lipolysis, hormonal and metabolic response to aerobic exercise depends on the individuals phenotype. Thus, exercise type, duration and intensity have to be strictly individualized in relation to phenotype in order to reach optimal metabolic benefits.
  • Preprint
    Purpose: This study investigated the effects of the menstrual cycle on running economy (RE). Method: Eleven eumenorrheic female athletes (mean age: 21.18 ± 3.65 years, height: 170.2 ± 6.6 cm, VO2max: 49.25 ± 9.15 mL·kg−1·min−1, and menstrual cycle: 29.8 ± 0.98 days) were tested for anthropometric variables, physiological responses (oxygen consumption [VO2], blood lactate [LA], heart rate [HR], and respiratory exchange ratio [RER]) at rest and while running. The RE was measured at speeds of 75%, 85%, and 95% of the lactate threshold at 3.5 mmol·L−1 during the follicular (FP) and luteal phases (LP) of the menstrual cycle. The RE was evaluated as oxygen consumption (mL·kg·min−1 [O2C_min], mL·kg−1·km−1 [O2C_km]) and caloric unit cost (kcal·kg−1·km−1 [EC]) during both phases. Results: There were no significant differences in body composition or resting physiological measurements between the LP and FP (p > .05). Physiological responses measured during RE tests were similar in both phases (p > .05). The RE measured as O2C_min, O2C_km, and EC was significantly lower during the LP than during the FP (p < .05). The RE defined as O2C_ min significantly increased with speed (p < .05), but RE defined as O2C_km and EC was unaffected by speed increment (p > .05). Conclusions: The RE is better in the LP than the FP and is independent of running speed when RE is evaluated as O2C_km and EC. The menstrual cycle had no effect on body composition and physiological variables measured at rest.
  • Article
    Fat and carbohydrate are the main sources of energy for consumption during rest, exercise and training activities, and they are related to factors like duration and intensity of exercise. The present study was designed to determine the maximal fat oxidation rate in untrained male students following an incremental training session. To do so, 9 untrained male students (VO2max: 36.58 ± 2.95 ml.kg.min and BMI 24.28 ± 1.83) took an incremental running test with 3 minute intervals on the treadmill. During the test, fat oxidation rate was measured using indirect stoichiometry method. Maximal fat oxidation and total fat oxidation rate variables were determined during this test. The mean value of fat oxidation rates were compared in 7 levels of exercise intensity with repeated measurement and LSD test. The results showed that maximal fat oxidation rate was 0.23±0.02 g.min in untrained subjects. The total fat oxidation rate in untrained subjects was 1.20 ± 0.13g/min. There was a significant different between the fat oxidation rate during 7 levels of exercise. Based on VO 2 max and HRmax percentage, the maximal fat oxidation was occur in 4272±301 percent of VO 2 max and 6009±337 percent of HRmax in untrained subjects. Based on the results, with increase the exercise intensity until Fatmax point the fat oxidation rates were increase and afterward that decrease in higher exercise intensity.
  • Article
    The purpose of this study was to determine appropriate intensity of activity with Fat max during incremental exercise in trained male subjects. To do so,11 trained male students (VO2max: 42.87±1.75ml.kg.min and BMI 21.40±1.01) took an incremental running test with 3 minute intervals on the treadmill.During the test, fat oxidation rate was measured using indirect stoichiometry method. Maximal fat oxidation and total fat oxidation rate variables were determined during this test.The mean value of fat oxidation rates were compared in 7 levels of exercise intensity with repeated measurement and LSD test. The results showed that maximal fat oxidation rate was0.29±0.03g.min in untrained subjects. The total fat oxidation rate in trained subjects was 1.47 ± 0.11g/min.There was a significant different between thefat oxidation rateduring 7 levels of exercise (p=0.001). Based on VO 2 max and HR max percentage, the maximal fat oxidation was occurring in40.09±2.58percent of VO 2max and 56.45±4.33percent of HR max in trained subjects. Based on the results, with increase the exercise intensity until Fat max point the fat oxidation rates were increase and afterward that decrease in higher exercise intensity.
  • Article
    Objective: The present study aimed to examine the interactive effect of exercise and energy balance on energy expenditure and substrate utilization. Method: Seven men and 7 women underwent three 2-day experimental protocols in a random order. Each protocol consisted of no exercise (NE), exercise only (EO), or exercise with a matched energy replacement (ER) on day 1 followed by metabolic testing that occurred after a 12-hour overnight fasting on day 2. Both EO and ER involved treadmill running at 60% maximal oxygen uptake (VO2max) that induced an energy expenditure of ∼ 500 kcal. The replacement meal used in ER contained ∼ 500 kcal made up of 45% carbohydrate, 30% fat, and 25% protein. During metabolic testing, oxygen uptake (VO2), heart rate (HR), respiratory exchange ratio (RER), and rates of carbohydrate (COX) and fat oxidation (FOX) were determined in three successive 15-minute periods including rest and exercise at 50% and 70% VO2max. Results: No differences in VO2 and HR were found at rest among NE, EO, and ER. However, RER was lower in EO than NE (0.840 ± 0.014 vs 0.889 ± 0.012, p < 0.05), COX (g·min⁻¹) was lower in ER than NE (0.144 ± 0.016 vs 0.197 ± 0.019, p < 0.05), and FOX (g·min⁻¹) was higher in EO or ER than NE (0.054 ± 0.010 or 0.057 ± 0.009 vs 0.034 ± 0.007, p < 0.05). No treatment effects were observed for all variables at either intensity. Conclusions: This study demonstrates that an exercise of moderate intensity can increase resting fat oxidation even when the exercise-induced energy expenditure is balanced by energy intake. This finding suggests that muscle action is vital in augmenting fat utilization.
  • Chapter
    Maintaining metabolic homeostasis is of paramount importance for the human organism. Accordingly, adenosine triphosphate (ATP) levels, the energy currency of the human body, are adequately maintained in skeletal and heart muscle by the continuous formation of ATP aerobically and anaerobically. The main substrates used for ATP formation are phosphocreatine, carbohydrates, and free fatty acids, while branched-chain amino acids contribute to a smaller extent. The main factor dictating the dominant metabolic pathway and the type of substrate used is exercise intensity, whereas other factors such as exercise duration, fitness status, gender, diet, and environmental conditions may also influence exercise metabolism. The metabolic pathways do not function independently. Rather, they interact via extracellular and intracellular signals from the exercising muscles and communicate with distant organs such as the liver, heart, and brain. Moreover, hormones secreted by cells of the endocrine system regulate activity of cells in other parts of the body, they can be released in response to exercise-induced stress, and, among other multiple functions, they modulate metabolism during exercise. Several clinical implications for health benefits of special populations rely on exercise metabolism alterations.
  • Article
    Most of the glycogen metabolism disorders that affect skeletal muscle involve enzymes in glycogenolysis (myophosphorylase (PYGM), glycogen debranching enzyme (AGL), phosphorylase b kinase (PHKB)) and glycolysis (phosphofructokinase (PFK), phosphoglycerate mutase (PGAM2), aldolase A (ALDOA), β-enolase (ENO3)); however, 3 involve glycogen synthesis (glycogenin-1 (GYG1), glycogen synthase (GSE), and branching enzyme (GBE1)). Many present with exercise-induced cramps and rhabdomyolysis with higher-intensity exercise (i.e., PYGM, PFK, PGAM2), yet others present with muscle atrophy and weakness (GYG1, AGL, GBE1). A failure of serum lactate to rise with exercise with an exaggerated ammonia response is a common, but not invariant, finding. The serum creatine kinase (CK) is often elevated in the myopathic forms and in PYGM deficiency, but can be normal and increase only with rhabdomyolysis (PGAM2, PFK, ENO3). Therapy for glycogen storage diseases that result in exercise-induced symptoms includes lifestyle adaptation and carefully titrated exercise. Immediate pre-exercise carbohydrate improves symptoms in the glycogenolytic defects (i.e., PYGM), but can exacerbate symptoms in glycolytic defects (i.e., PFK). Creatine monohydrate in low dose may provide a mild benefit in PYGM mutations.
  • Article
    Background: The purpose of this study was to determine appropriate intensity of activity with FAT max during incremental exercise in the active and sedentary male participants. Material and methods: In this study, 11 active male students(VO 2max 42.87±1.75ml.kg-1 .min-1 ,BMI 21.40±1.01 kg.m 2) and 9 sedentary male students(VO 2max 36.57±2.95ml.kg-1 .min-1 , BMI 24.28±1.83kg.m 2) were selected as the active and sedentary groups. Participants performed an incremental test with three minutes intervals on the treadmill. Exercise intensity was measured in all phases by measuring oxygen consumption. Also, heart rate and the fat oxidation was measured using indirect calorimetric. Independent t-test was used to compare the mean FAT max in the two groups. Also two-way analysis of variance(ANOVA) with repeated measurements was used to compare FAT max at 7 levels of exercise intensity between the two groups at α≤0.05 confidence interval level. Also, the Pearson correlation coefficient was used to measure the relationship between VO 2max and maximal fat oxidation(MFO). Results:There was no significant difference between FAT max of the active and sedentary groups, in terms of VO 2max and HR max percentage, but the difference between MFO in the active and sedentary groups was significant(p=0.001). The results also showed that there are significant differences in fat oxidation during 7 levels of intensity training between the active and sedentary males(p=0.001). Also, there was a significant correlation between VO 2max and FAT max of two groups(p=0.002). Conclusion: Based on the results, it can be concluded that the active participants, due to their physiological adaptations with exercise, showed significant higher fat oxidation at FAT max point and all phases of exercise intensity.
  • Bipsies were obtained from the gastrocnemius muscle of 13 male and 12 female distance runners and analyzed for [14C]palmitoyl-CoA oxidation, fiber composition, and the activities of selected enzymes. The male and female runners were similar in terms of maximal oxygen uptake (VO2max), training mileage, fiber compositions, and data collected during a 60-min treadmill run at 70% VO2max. Muscle succinate dehydrogenase and carnitine palmitoyl transferase activities were, however, significantly greater (P less than 0.05) in the male than in female runners. In addition, the male runners' muscle also showed a greater capacity to oxidize palmitoyl CoA. Little relationship, however, was found between muscle lipid metabolism, enzyme activities, and the calculated (respiratory exchange) fraction of energy derived from fat during 60 min of running at 70% VO2max. Although these data support the concept that endurance training (80-115 km/wk) markedly enhances the capacity of muscles to metabolize fats, the factors that regulate the usage of lipids during prolonged exercise do not appear to be limited by the capacity of the fibers to oxidize fatty acids, as determined by in vitro measurements.
  • Article
    Full-text available
    A new stable isotope method for the determination of substrate oxidation rates in vivo is described and compared with indirect calorimetry at rest and during high-intensity exercise (30 min at 80-85% maximal O2 uptake capacity) in six well-trained cyclists. This method uses the absolute ratios of 13C/12C in expired air, endogenous glucose, fat, and protein in addition to O2 consumption and is independent of CO2 production (VCO2). Carbohydrate and fat oxidation rates at rest, calculated by both methods, were not significantly different. During exercise the breath 13C/12C ratio increased and reached a steady state after 15-20 min. Carbohydrate oxidation rates during exercise were 39.4 +/- 5.2 and 41.7 +/- 5.7 mg.kg-1.min-1 [not significant (NS)], and fat oxidation rates were 7.3 +/- 1.3 and 6.9 +/- 1.2 mg.kg-1.min-1 (NS), using indirect calorimetry, and the breath ratio method, respectively. We conclude that the breath 13C/12C ratio method can be used to calculate substrate oxidation under different conditions, such as the basal state and exercise. In addition, the results obtained by this new method support the validity of the underlying assumption that indirect calorimetry regards VCO2 as a reflection of tissue CO2 production, during exercise in trained subjects, even up to 80-85% maximal O2 uptake.
  • Article
    We investigated the hypothesis that the increase in lipolysis that occurs in short-term (86-h) fasting is due to a decreased inhibitory influence of adenosine. In normal volunteers who fasted for 14 and 86 h, the response to adenosine receptor blockade was assessed by the infusion of theophylline at a rate sufficient to produce plasma concentrations (30 microM) that blocked adenosine receptors but that were well below the threshold for inhibition of phosphodiesterase. Lipolysis was assessed by determining the rate of appearance of glycerol using D-5-glycerol infusion. Fatty acid flux was also determined by means of [1-13C]palmitate infusion, and total fatty acid oxidation was determined by indirect calorimetry. There was a mild stimulatory effect of theophylline on lipolysis at 14 h. After the subjects fasted for 86 h, theophylline infusion caused a much greater increase in both lipolysis and fatty acid oxidation. These results suggest that the inhibitory effect of adenosine on lipolysis is increased during short-term fasting.
  • Article
    To evaluate the metabolic consequences of short-term (i.e., less than 24 hours) starvation, glucose and fat metabolism were studied in eight healthy subjects and in eight patients with stable cirrhosis after 16-hour and again after 22-hour starvation by 3-[3H]glucose and [14C]palmitate turnover and by indirect calorimetry. Although patients and controls showed significant increases in free fatty acid concentration (respectively, 48% +/- 12% and 53% +/- 17%) and turnover (55% +/- 14% and 71% +/- 21%) during short-term starvation, the values after 16- and after 22-hour starvation were higher in cirrhosis. Fat oxidation was enhanced in the patients, but did not increase during fasting in contrast to controls (increase 19% +/- 17%, P less than 0.05). Net glucose oxidation was decreased in postabsorptive cirrhotics (P less than 0.05). Although postabsorptive glucose turnover was not different from controls, starvation induced a greater decrease in glucose turnover in the patients (25% +/- 3% vs. 10% +/- 3%, P less than 0.05). This was not reflected in plasma glucose concentrations. In conclusion, the effects of starvation on glucose and fat metabolism are enhanced in cirrhosis; fasting hypoglycemia is prevented by decreased use of glucose. It remains to be established whether these changes are merely explained by defective liver function, per se.
  • Article
    The effects of gender on substrate utilization during prolonged submaximal exercise were studied in six males and six equally trained females. After 3 days on a controlled diet (so that the proportions of carbohydrate, protein, and fat were identical), subjects ran on a treadmill at a velocity requiring an O2 consumption of approximately 65% of maximal. They ran a total "distance" of 15.5 km with a range in performance time of 90-101 min. Plasma glycerol, glucose, free fatty acids, and selected hormones (catecholamines, growth hormone, insulin, and glucagon) were measured throughout and after the run by sampling from an indwelling venous catheter, and glycogen utilization was calculated from pre- and postexercise needle biopsies of vastus lateralis. Exercise protein catabolism was estimated from 24-h urinary urea nitrogen excretion over the test day and a nonexercise day. The males were found to have significantly higher respiratory exchange ratios (mean 0.94 vs. 0.87), greater muscle glycogen utilization (by 25%), and greater urea nitrogen excretion (by 30%) than the females. No gender differences were evident in the hormonal response to the exercise with the exception of a lower insulin concentration and a higher epinephrine concentration in the males. We conclude that, during moderate-intensity long-duration exercise, females demonstrate greater lipid utilization and less carbohydrate and protein metabolism than equally trained and nourished males.
  • Article
    Full-text available
    Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2-[13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3-methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/- 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery.
  • Article
    Whole-body lipolytic rates and the rate of triglyceride-fatty acid cycling (reesterification of fatty acids released during lipolysis) were measured with stable isotopic tracers in the basal state and during beta-adrenergic blockade with propranolol infusion in five cachectic patients with squamous cell carcinoma of the esophagus, five cachectic cancer-free, nutritionally-matched control patients, and 10 healthy volunteers. Resting energy expenditure and plasma catecholamines were normal in all three groups. The basal rate of glycerol appearance in blood in the patients with cancer (2.96 +/- 0.45 mumol.kg-1.min-1) was similar to that in the nutritionally matched controls (3.07 +/- 0.28 mumol.kg-1.min-1), but 48% greater than in the normal-weight volunteers (2.00 +/- 0.16 mumol.kg-1.min-1) (P = 0.028). The antilipolytic effect of propranolol and the rate of triglyceride-fatty acid cycling in the patients with cancer were also similar in the cachectic control group and approximately 50% greater than in the normal-weight volunteers, but the differences were not statistically significant because of the variability in the data. We conclude that the increase in lipolysis and triglyceride-fatty acid cycling in "unstressed" cachectic patients with esophageal cancer is due to alterations in their nutritional status rather than the presence of tumor itself. Increased beta-adrenergic activity may be an important contributor to the stimulation of lipolysis.
  • Article
    The hepatic glucose cycle involves the production of plasma glucose from glucose 6-phosphate and the simultaneous conversion of glucose back to glucose 6-phosphate. We have evaluated the role of the glucose cycle in the regulation of plasma glucose concentration during exercise at 70% of maximal O2 uptake and during recovery in five normal volunteers. Total glucose flux was measured by use of [2-2H]glucose (Ra2), net glucose flux through the glucose cycle was determined with [6,6-2H2]glucose (Ra6), and the rate of glucose cycling was determined by Ra2 - Ra6. Gas chromatography-mass spectrometry was used for analysis of isotopic enrichment. At rest, 33% of total glucose flux was recycled. In exercise, total flux increased 300%, but so did glucose cycling, which means that there was no change in the percentage of flux recycled. In recovery, both total flux and the rate of recycling returned rapidly to the resting value. We therefore conclude that whereas total glucose production can respond extremely quickly to large changes in energy requirements caused by exercise, thereby enabling maintenance of a constant blood glucose concentration, glucose cycling does not have an important role in amplifying the control of net hepatic glucose flux through the glucose cycle.
  • Article
    In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion (0.015 microgram X kg-1 X min-1) were determined. The rate of appearance (Ra) of free fatty acids (FFA) and glycerol were quantified by infusion of [1-13C]palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H2(18)O dilution. In normal volunteers, the basal Ra FFA and Ra glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting.