1 Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4; and 2 Department of Biology, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5
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ABSTRACT |
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Relative exercise intensity (or %maximum
O2 consumption,
O2 max)
controls fuel selection at sea level (SL) and after high-altitude acclimation (HA) in rats. In this context we used indirect calorimetry, [1-14C]palmitate
infusions, and muscle triacylglycerol (TAG) measurements to determine
1) total lipid oxidation,
2) the relationship between circulatory nonesterified fatty acid (NEFA) flux and concentration, and
3) muscle TAG depletion after
exercise in HA-acclimated rats. Aerobic capacity is decreased in
trained rats after 10 wk of acclimation. Both SL and HA showed the same
relative use of lipids at 60% [62 ± 5% (HA) and 61 ± 3% (SL) of O2 consumption
(
O2)] and 80%
[46 ± 6% (HA) and 47 ± 5% (SL) of
O2] of their
respective
O2 max. At
60%
O2 max,
plasma [NEFA] were higher in HA, but rate of appearance was
essentially the same in both groups (at 30 min, 38 ± 9 vs. 49 ± 6 µmol · kg
1 · min
1
in HA and SL, respectively). At this intensity SL showed no significant decrease in muscle TAG, but in HA it decreased by 64% in soleus and by
90% in red gastrocnemius. We conclude that
1) the relative contributions of
total lipid are the same in SL and HA, contrary to differences in
[NEFA], because the relationship between flux rate and
[NEFA] is modified after acclimation, and
2) muscle TAG may play a more
important role at HA.
rats; maximum exercise intensity; lipid metabolism; nonesterified fatty acids; carbohydrates; oxidative fuel; muscle triacylglycerol
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INTRODUCTION |
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LIPIDS represent an abundant source of oxidative fuel
for muscle contraction, and body stores of triacylglycerol can sustain low-intensity exercise for several days (17). At high altitude (HA), an
increased use of lipids has been thought to be advantageous during
exercise to spare valuable and limited stores of muscle glycogen (48).
Increases in plasma nonesterified fatty acid concentrations
[NEFA] have often been interpreted as an increase in lipid
oxidation (20, 48) because of the correlation between concentration and
flux during low-intensity exercise at sea level (15, 31).
Extrapolations from concentration measurements can be misleading (46),
and it is not known whether the relationship between [NEFA]
and flux is the same at sea level and HA. For instance, some studies on
training in humans have shown a decrease in [NEFA] but an
increase in fat oxidation during exercise (22, 25). Increases in
[NEFA] can arise from a mismatch between rate of appearance
from adipose tissue (Ra) and
rate of disappearance into muscle
(Rd). Such a mismatch can in
part be caused by a decrease in the triacylglycerol-fatty acid (TAG-FA)
cycle (47) and is not necessarily linked to increased oxidation. There
is also no direct information on the effect of HA acclimation on muscle
TAG utilization. Carbohydrates (CHO) provide a higher yield of ATP per
mole of oxygen and for this reason have been viewed as a preferred fuel
source during exercise after HA acclimation (18). However, we have
recently shown that the contributions of total CHO, circulatory glucose, and muscle glycogen to overall metabolism are not altered by
acclimation when control and acclimated animals are compared at the
same relative exercise intensity (%maximum
O2 consumption, O2 max) (28). Thus the
O2-saving advantage of CHO seems
to be outweighed by limited availability of this critical fuel source. Consequently, the contribution of total lipid oxidation to total metabolic rate is also the same before and after acclimation. In this
context, the effect of acclimation on the use of lipids and its
different sources has not been studied systematically, and the
potential effects of chronic exposure to hypoxia warranted closer examination.
%O2 max is the major
determinant of CHO and lipid utilization after HA acclimation in rats
(28) as well as at sea level in other quadrupeds (36) and humans (7).
In previous HA acclimation studies, comparisons have been made at the
same absolute exercise intensity (i.e., same work rate; e.g., see Ref.
6). The decrease in aerobic capacity or
O2 max associated with
HA acclimation (8, 28) makes absolute work rates a higher
%
O2 max in
HA individuals. This has important implications, because maximal rates
of lipid oxidation are reached at low exercise intensities (30-60%
O2 max,
depending on species and gender), whereas the relative importance of
CHO increases with exercise intensity, ultimately providing 100% of
the energy at
O2 max
(36). Therefore, the increases in CHO or decreases in lipid oxidation
observed in previous acclimation studies (6, 34) may have been due to
experimental design and not necessarily acclimation. Here, we used
indirect calorimetry and continuous tracer infusions to quantify lipid
oxidation and NEFA turnover rate in HA-acclimated and sea level control
(SL) rats exercising at the same
%
O2 max. Changes in muscle TAG after exercise were also measured to estimate the
contribution of intramuscular lipids. The goals of this study were to
determine 1) whether the
relationship between NEFA flux and NEFA concentration is the same at SL
and HA and 2) whether exercise
causes the same depletion of muscle TAG reserves at SL and HA. In
addition, we were able to estimate the relative contributions of
circulatory and intramuscular lipids during exercise in both groups of animals.
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METHODS |
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Animals. The methods used for acclimation, training, and surgery in these experiments have been described elsewhere (28). This study has been approved by the animal ethics committees of the Universities of British Columbia and Ottawa. Thirty-two female Wistar rats were randomly assigned to one of two groups, one kept at SL conditions [fractional concentration of inspired O2 (FIO2) = 0.2094] and the other under hypobaric hypoxia simulating HA conditions (FIO2 = 0.12, equivalent to 4,300 m). Starting body mass (Mb) at 5-6 wk of age was 231 ± 2 g (HA) and 225 ± 2 g (SL). Each group was given free access to food (Rodent Lab Diet, PMI Nutrition, St. Louis, MO) and water. Both groups were kept under a 12:12-h light-dark photoperiod and were housed in groups of 2 or 4 per cage at 25°C. Mb at the time of experiments was not significantly different (P = 0.21) between SL at 302 ± 6 and HA at 289 ± 14 g (28).
HA rats were acclimated to HA conditions in specially designed hypobaric chambers. The barometric pressure was decreased progressively (4) over the first 10 days of acclimation to a final value of 450 mmHg by use of an oil-less vacuum pump, as described elsewhere (28). Rats were kept at this pressure forRespirometry.
Measurements of mass-specific O2
consumption (O2) and
CO2 production
(
CO2) were made with a
flow-through respirometry system (Sable Systems TR-3, Henderson, NV).
Exercise measurements were made in a Plexiglas-enclosed motorized
treadmill equipped with electric stimulus (Columbus Instruments,
Columbus, OH).
O2,
CO2, and respiratory
exchange ratio (RER) measurements were found to be accurate to ±1%
(n = 3) by burning methanol.
O2 max was
measured for each animal (SL rats under normoxic conditions, HA rats
under hypoxic conditions and after acclimation was complete). The three
criteria used to determine when the animals had reached
O2 max were
1) no change in
O2 as speed was increased,
2) the animals could no longer keep
their position on the treadmill, and
3) the RER
(
CO2/
O2)
reached a value greater than 1 (38).
O2 max in acclimated
(HA) rats was found to be 24% lower than in SL rats (67.6 ± 1.3 vs. 89.3 ± 1.2 ml · kg
1 · min
1)
(28).
Exercise protocols.
For all protocols, HA were run at
FIO2 = 0.12 and SL were run
at FIO2 = 0.2094 after an
overnight fast. Running speeds corresponding to 60 and 80%
O2 max were
calculated for each individual. Values of
O2 and
CO2 were continuously measured for 50 or 60 min at 60%
O2 max and for 25 or
30 min at 80%
O2 max.
Measured intensities were 53.9 ± 0.4 and 57.1 ± 0.5%
O2 max and 78.7 ± 1.2 and 75.7 ± 0.6%
O2 max for
SL and HA, respectively.
NEFA kinetics.
NEFA kinetics were only quantified at the lower exercise intensity of
60% O2 max because
of the more invasive nature of these measurements. After completion of
the respirometry measurements, the animals were transferred to the
University of Ottawa and allowed to recover for a minimum of 5 days.
Upon arrival, HA rats were immediately placed again in hypobaric
chambers. Jugular vein and carotid artery catheters were implanted
under halothane anesthesia, and the animals were allowed to recover for
3-6 days, as previously described (28). Training was suspended for
both HA and SL during this period.
Tissue sampling.
Two additional groups of rats were trained for 10 wk as described for
the two experimental groups. One-half of the animals in each group
underwent HA acclimation for 10 wk. Animals were euthanized (sodium
pentabarbitol at 20 mg/100 g) after an overnight fast, and resting
samples were taken from the soleus, plantaris, and red and white
portions of gastrocnemeus muscles from the left hindlimb and were
quickly frozen using precooled aluminum clamps. Postexercise samples
were obtained immediately after 60 min of exercise at 60%
O2 max. Tissues were
stored at
80°C until analysis.
Sample analysis. Plasma NEFA concentrations were measured on one resting sample and all other samples using a Hewlett-Packard 5890 series II gas chromatograph (GLC) equipped with a 30-m fused silica capillary column (Supelco SP-2330) kept at 185°C for 34 min, raised to 210°C at 5°C/min, and kept at 210°C for 11 min. The system was also equipped with an automatic injection system (HP 7673). NEFA were extracted and methylated from 75 µl of plasma by a modification of the method of Tserng et al. (43), previously used in other mammals (26, 27). The GLC was calibrated with known standards (PUFA-2, Matreya), and heptadecanoic acid (17:0) was added as an internal standard. [1-14C]palmitate activity was measured with a Tri-Carb 2500 counter on 30 µl of plasma after drying under N2, resuspension in 1 ml H2O, and addition of ACS-II scintillant (Amersham).
Tissue TAG concentrations were determined as previously described (10). Tissue samples (100-300 mg) were powdered in a liquid N2-cooled mortar and transferred into preweighed glass tubes. The samples were homogenized in a chloroform-methanol (Folch 1:1, vol/vol) solution (9) at 30 ml/g tissue. The homogenizer was rinsed with 1 ml of Folch 1:1, which was added to the homogenate. Lipids were extracted by shaking at room temperature for 20 min. The homogenate was centrifuged at 3,000 rpm for 10 min, the pellet was washed with another 1 ml of Folch 1:1 and centrifuged, and the supernatants were pooled. Chloroform was then added at 0.5 times the final volume to bring the Folch solution to a ratio of 2:1. A 0.2% KCl solution was added at 0.25 times the final volume, and after centrifugation the aqueous phase was discarded. Two to three milliliters of ethanol (99%) were added to the remaining organic phase before drying under N2 at 40°C. The lipids were redissolved in 250 µl or 500 µl of isopropanol, and TAG concentration was measured spectrophotometrically (Perkin-Elmer Lambda 2 UV/VIS) at 540 nm with a diagnostic kit (Sigma, St. Louis, MO). A subsample (15-50 mg) of each powdered tissue was transferred to a preweighed glass tissue grinder and homogenized in 19 volumes of freezable buffer (16). Protein concentrations were determined by plate reader (Molecular Devices, Thermomax) microassay at 600 nm with a kit (Bio-Rad). This was used to express TAG in the more reliable units of micromoles per gram of protein (12).Calculations and statistics.
Values for O2 and
CO2 were calculated using
the equations of Withers (45) and converted micromolar units
(
O2
and
CO2). Total lipid oxidation measured by indirect calorimetry was calculated with the equations of Frayn (11), with the assumption that the contribution of proteins to overall energy expenditure was negligible during exercise in the postabsorptive state (33).
Ra palmitate rates were calculated
using steady-state calculations of Steele (40) previously validated for
fatty acid kinetics (30). Ra NEFA
was calculated by using the percent contribution of palmitate to total
NEFA concentration determined by GLC. Hypothetical relative circulatory
NEFA oxidation rates were calculated on the basis of 23 moles of oxygen
per mole of palmitate (29) and were converted to NEFA oxidation using
the percent contribution of palmitate and then expressing the result as
a percentage of total
O2. Results were analyzed using a t-test
and a one- or two-way analysis of variance (ANOVA). When tests for
normality failed, a Mann-Whitney Rank-Sum Test or a Kruskal-Wallis
ANOVA was used. Pair-wise multiple comparisons were made by the
Student-Newman-Keuls test or by Dunnett's method. All percentages were
arcsine square root transformed. Values are means ± SE.
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RESULTS |
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Respirometry and CHO oxidation.
O2,
CO2,
RER, and CHO oxidation are summarized in Table
1. Briefly,
O2
and
CO2
were greater in SL than in HA at both 60 and 80%
O2 max. HA acclimation
did not have a significant effect on RER, an indicator of fuel
preference, which increased from 60 to 80%
O2 max. CHO oxidation
was higher in SL than in HA, but when corrected to total metabolic rate
(
O2),
there was no difference in the contribution of CHO to overall
metabolism. As indicated by RER values, CHO oxidation increased as
exercise intensity increased from 60 to 80%
O2 max (Table 1).
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Total lipid oxidation.
During exercise at 60%
O2 max, lipid oxidation
rates were lower in HA than in SL (P < 0.0001, ANOVA). Oxidation rates ranged from 1,366 ± 58 to 1,695 ± 66 µmol
O2 · kg
1 · min
1
in SL and 1,126 ± 95 to 1,432 ± 49 µmol
O2 · kg
1 · min
1
in HA (Fig.
1A).
However, the percent contribution of lipid oxidation to total
O2
was not significantly different between the two groups
(P = 0.21; Fig.
1B). Over 50 min of exercise, it
ranged from 61 ± 3 to 80 ± 2% in SL and 62 ± 5 and 84 ± 2% in HA. At 80%
O2 max, lipid oxidation
rates were not different in the two groups
(P > 0.05; Fig
2A).
Lipid oxidation rates did not change significantly over time in HA,
ranging from 984 ± 1,123 to 985 ± 76 µmol
O2 · kg
1 · min
1
over the course of the exercise bout. SL values, on the other hand,
increased over the exercise period from 737 ± 184 to 1,466 ± 102 µmol
O2 · kg
1 · min
1
(Fig. 2A). At the beginning of
exercise (10 min mark), lipid oxidation accounted for 47 ± 6% of
total
O2
in HA but only 27 ± 7% in SL (P = 0.03). At 20 min there was no significant difference between SL and HA
(P = 0.57). There was little change in
lipid contribution in HA and at the end of exercise at 46 ± 6%,
whereas it rose in SL to 47 ± 5% (Fig.
2B). When compared at the same absolute average speed of 17.2 m/min, the HA rats had a lower rate of
lipid oxidation (P < 0.0001) and
percent contribution to total
O2
(47 ± 6 to 46 ± 6%) than in SL (61 ± 3 to 80 ± 2%; Fig. 3,
A and
B).
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Palmitate and NEFA turnover.
Concentration determined by GLC, specific activity of
[1-14C]palmitate, and
Ra of palmitate all appear in Fig.
4,
A - C.
Resting palmitate concentrations were higher in HA (356 µmol/l) than
in SL (239 µmol/l) (P < 0.0001)
and remained constant during exercise. Both groups showed a large and
significant increase in palmitate concentration after exercise had
stopped (P < 0.05).
Ra, however, dropped from an
average resting value of 16.2 to 11.3 µmol · kg1 · min
1
during exercise in HA but remained constant in SL (15.4 to 14.4 µmol · kg
1 · min
1;
Fig. 4, A and
C). Turnover of palmitate was lower
in HA during exercise but not significantly different from SL.
Similarly, NEFA concentrations were higher in HA than in SL (1,193 ± 85 to 1,207 ± 51 µmol/l in HA and 994 ± 108 to 795 ± 64 µmol/l in SL from rest to 60 min of exercise;
P < 0.05). The NEFA
Ra was lower in HA (but
nonsignificant; P = 0.11) compared
with SL at 30 min (38 ± 9 vs. 49 ± 6 µmol · kg
1 · min
1),
45 min (32 ± 7 vs. 46 ± 9 µmol · kg
1 · min
1),
and 60 min (29 ± 6 vs. 45 ± 12 µmol · kg
1 · min
1;
Fig. 5, A
and B).
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NEFA concentrations and composition.
At rest, the plasma concentration of all individual FA contributed to
the higher total [NEFA] in HA rats, and the percent contributions of stearate (18:0) and oleate (18:1) were different between the groups (Table 2; Fig. 5).
Throughout exercise and recovery, the percent contribution of palmitate
(16:0) to total NEFA does not deviate from ~30% despite changes in
absolute concentrations (Table 2 and Fig. 5). However, 18:1 and 18:0
showed changes in both concentration and percent contribution to total
NEFA between rest, exercise, and recovery as well as between HA and SL
(Table 2).
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Muscle TAG.
TAG concentrations were determined in soleus, plantaris, and red and
white portions of the gastrocnemius at rest and after 60 min at 60%
O2 max (Fig.
6). There was no significant difference in
resting levels of TAG between the two groups. SL rats showed a decrease
in TG of 42% in soleus and 64% in white gastrocnemius after exercise,
but neither value was significantly different from resting level. HA
did show a significant decrease (P < 0.05) in soleus (100 ± 19 to 42 ± 11 µmol/g
protein) and red gastrocnemius (14.02 ± 0.83 to 1.4 ± 0.02 µmol/g protein) in TAG after 60 min at 60%
O2 max (Fig. 6).
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DISCUSSION |
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This study shows that, in an animal model, relative exercise intensity
is the major determinant of lipid utilization after HA acclimation.
Contrary to previous studies on men (6, 34, 35), we found in rats that
there was no change in the relative contribution of lipids after
prolonged exposure to hypoxia. Trained female HA and SL rats exercising
at 60 and 80% of their
O2 max derive the same
fraction of their total energy from lipid oxidation (Figs.
1B and
2B). Higher [NEFA] seen
after HA acclimation suggested an increase in lipid utilization, but
flux rates were not different from those of SL (Fig. 5). Therefore, the
correlation between concentration and flux seen at SL was not observed
after HA acclimation. The contributions of circulatory NEFA and
intramuscular TAG may be different before and after HA acclimation. The
greater depletion of muscle TAG seen in HA soleus and red gastrocnemius
(Fig. 6) suggests that this fuel source may be more important in this
group. Along with our earlier findings on CHO oxidation (28), we have demonstrated that
%
O2 max, not
acclimation, is the main determinant of whole animal oxidative fuel
selection at HA. Therefore, current general models of fuel selection at
SL, drawn from animals and humans (7, 36), apply to these HA
acclimation experiments. Previous studies on men made comparisons at
the same absolute speed that represented a higher percentage of
O2 max for the HA
group. This resulted in HA groups using lower proportions of lipid,
most likely as a consequence of experimental design, as shown here when
HA and SL were compared at the same speed of 17.2 m/min (80 and 60%
O2 max in HA
and SL, respectively; Fig. 3, A
and B). Recent findings on humans
suggest that this pattern does not hold true in trained vs. untrained
men (3) and in men vs. women (13, 19) at the same relative exercise
intensity. Therefore, in fuel selection studies, training status and
gender appear to be as important as exercise intensity to
considerations of experimental design.
Total lipid oxidation.
Increasing lipid oxidation can have at least two obvious advantages:
1) improving endurance to take
advantage of large adipose tissue stores and/or
2) sparing valuable muscle glycogen:
the only fuel available for high-intensity exercise. Here, we found that neither of these potential benefits was directly exploited, because total lipid oxidation contributed equally to overall metabolism in HA and SL (Figs. 1 and 2). However, the fact that lipid oxidation did not decrease (as expected, if the higher ATP yield per
O2 of CHO were exploited) could be
interpreted as a glycogen-sparing mechanism. The relative contribution
of lipids was higher in HA than in SL at the beginning of exercise at
80% O2 max, so there may be, under these circumstances, active sparing of glycogen (Fig.
2B). Why not rely even more on
lipids than observed here and be able to power locomotion for several
days on adipose tissue reserves to spare glycogen even further? Part of
the answer may lie in the inability to sustain high power outputs
through lipid oxidation (32), which reaches maximal rates at low
relative work rates. Lipid oxidation usually does not increase above
60-65%
O2 max (dogs,
goats, and men), and the contribution of this fuel to total energy
expenditure declines as exercise intensity increases (36, 37, 44). HA
and SL rats showed no increase in lipid oxidation from 60 to 80%
O2 max (Figs.
1 and 2), but this maximum rate may have been reached at a
lower intensity. Recent studies on women show that they can maintain
higher lipid oxidation rates than men at the same relative exercise
intensity (13, 19, 41). This may explain lower RER values seen for female rats (Table 1) compared with literature values for human males.
The upper limit for lipid oxidation may be related to energetic constraints set by the lower yield of ATP per mole of
O2, or perhaps the fibers
recruited at these intensities (type I and type IIa) are specialized
for fat use and uptake (5), whereas the fibers recruited for more rapid
work are geared for a higher glycolytic capacity (type IIb). The
characteristics of the muscles recruited at these intensities
[predominantly soleus, plantaris, and red gastrocnemius in SL
rats (23)] appear to change little after HA acclimation.
Postacclimation in rats, there are equivalent amounts of 3-hydroxy
acyl-CoA dehydrogenase, a
-oxidation enzyme, in soleus and
plantaris, and the conservation of fiber typology of the plantaris
compared with SL (1). In any case, the reliance on lipids is neither
increased nor decreased after HA acclimation, even though a decline in
relative lipid use (compensated by an increase in relative CHO use)
would allow animals to maintain the same rate of aerobic ATP production
with a lower O2 consumption.
NEFA turnover.
Plasma [NEFA] was substantially higher in HA than in SL at
rest, during exercise at 60%
O2 max, and
in postexercise recovery (Fig. 5A).
Except for a sharp rise at the beginning of recovery, these values were
not affected by exercise. All of the individual NEFA measured
contributed to the higher NEFA in HA, but not equally, as shown by
differences in percent contribution of 18:0 and 18:1 to total NEFA
between the two groups. Palmitate appears to be an appropriate tracer
for total NEFA in HA acclimation turnover experiments, as it deviates
little from 30% of total NEFA at rest, during exercise, or in recovery
(Table 2). Nonruminant mammals with the same diet should show similar
plasma NEFA composition (2), but this is clearly not the case in rats
after acclimation. Differences seen in stearate (18:0) and oleate
(18:1) point to potential changes in stearyl desaturase activity in
liver with acclimation. This enzyme has not been studied after HA
acclimation. This is an area in need of further research, as it may
indicate differential incorporation of NEFA into adipose tissue and
muscle TAG. Fasting before each experiment also played a part in the high [NEFA] seen in both groups. Suprisingly,
Ra NEFA was the same or even
tended to be lower in HA than in SL during exercise and recovery (Fig.
5B), and these changes in flux were,
therefore, independent of plasma concentration. This blunted turnover
could not be the result of hyperglycemia or lactate, because plasma glucose and lactate concentrations, measured simultaneously, were the
same in the two groups (28). Consistently higher [NEFA] despite similar resting and lower or similar exercise/recovery fluxes
contradicts the accepted dogma that concentration and flux are
positively correlated during exercise (31). Moreover, other recent
experiments have shown that endurance training causes a decrease in
plasma [NEFA], together with an increase in lipid utilization (25). Therefore, extrapolation from [NEFA] to
turnover rate should clearly be avoided. Interestingly, this study is
the first to directly quantify the effects of HA acclimation on NEFA fluxes. Other investigations investigating the impact of acclimation on
fat metabolism (34, 48) have based their conclusions on observed
changes in plasma concentrations. We would probably have interpreted
our results as an increase in NEFA utilization after HA acclimation,
had we relied exclusively on concentration measurements.
Muscle TAG utilization. SL rats showed no significant decrease in TAG with exercise (Fig. 6). This is in contrast to studies on rats that use tetanic stimulation (39) and treadmill exercise (14) but is consistent with a recent finding on humans, in which there was no decrease in muscle TAG until exercise had finished (21). HA rats showed a decrease in TAG with exercise in soleus and red gastrocnemius. This, along with lower circulatory NEFA turnover, suggests that muscle TAG utilization is increased at HA. Based on blood flow measurements (23), soleus and red gastrocnemius muscles are recruited at this exercise intensity at SL. It is not known whether this is true for HA and suggests that comparisons of muscle recruitment patterns before and after HA acclimation warrant closer examination.
To provide a first estimate of the relative contributions of circulatory and intramuscular lipid sources, we need an estimate of circulatory NEFA oxidation rates. If we assume that 100% of the NEFA entering the circulation (Ra) are oxidized by working muscles, they would account for the same proportion of total energy expenditure in HA and SL. By the end of exercise, circulatory NEFA could account for maximally 46 ± 9 and 46 ± 13% ofConclusions and implications. This is the first study to show that total lipid utilization during exercise is unchanged after altitude acclimation. Using the rat as an animal model and eliminating the influence of exercise intensity, this study and our previous work on CHO reveal a more comprehensive picture of high-altitude fuel selection. So far, we have shown that a compromise must be struck in hypoxic environments between the O2-saving advantage of increased CHO use and the glycogen-sparing advantage of increased lipid use. One implication is that glycogen apparently is a crucial substrate, and its use during exercise is minimized at altitude by not increasing CHO metabolism beyond SL values (28). Interestingly, muscle TAG may be a more important fuel under these conditions, as shown by a greater depletion of TAG and a blunted plasma NEFA turnover rate during exercise after acclimation. Further work will be needed to assess whether this observed pattern of fuel selection can be generalized to all mammals.
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ACKNOWLEDGEMENTS |
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We thank Kim Yates for performing the rat surgeries and Dr. Fiona Fisher for helpful veterinary advice. Dr. Wade Parkhouse kindly provided an 8-lane treadmill, and Nadine Ho helped with rat training used for triacylglycerol measurements.
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FOOTNOTES |
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This study was funded through National Sciences and Engineering Research Council (NSERC) operating grants to J.-M. Weber and P. W. Hochachka. During this study G. B. McClelland was supported by an NSERC postgraduate scholarship.
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 correspondence and reprint requests: G. McClelland, Dept. of Zoology, Univ. of British Columbia, 6270 Univ. Blvd., Vancouver, BC, Canada V6T 1Z4 (E-mail: mcleland{at}interchange.ubc.ca).
Received 24 August 1998; accepted in final form 29 July 1999.
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