Regulation of fatty acid oxidation in untrained vs. trained
men during exercise
Labros S.
Sidossis,
Robert R.
Wolfe, and
Andrew R.
Coggan
Metabolism Unit, Shriners Burns Institute, and the Departments of
Surgery and Anesthesiology, University of Texas Medical Branch,
Galveston, Texas 77550
 |
ABSTRACT |
We have recently shown that increased
carbohydrate flux decreases fat oxidation during exercise by inhibition
of fatty acid entry into the mitochondria. Because endurance training
reduces the rate of carbohydrate flux during exercise, we hypothesized that training increases fat oxidation by relieving this inhibition. To
test this hypothesis, five sedentary and five endurance-trained men
exercised on a cycle ergometer at an oxygen consumption
(
O2) of ~2.0 l/min,
representing 80 and 40% peak
O2, respectively. [1-13C]oleate and
[1-14C]octanoate,
long- and medium-chain fatty acids, respectively, were infused for the
duration of the studies. Carbohydrate oxidation was significantly
higher in the sedentary group (196 ± 9 vs. 102 ± 17 µmol · kg
1 · min
1,
P < 0.05). Oleate oxidation was
higher in the trained group (3.8 ± 0.6 vs. 1.9 ± 0.3 µmol · kg
1 · min
1,
P < 0.05), whereas octanoate
oxidation was not different between the two groups. The percentage of
oleate that was taken up by tissues and oxidized was higher in the
trained group (76 ± 7 vs. 58 ± 3%,
P < 0.05). However, the percentage
of octanoate taken up and oxidized was not different (82 ± 3 vs. 85 ± 4%, not significant). Because octanoate, unlike oleate, can
freely diffuse across the mitochondrial membrane, the present results
suggest that the difference in fatty acid oxidation between trained and
untrained individuals may be due to enhanced fatty acid entry into the
mitochondria.
mitochondria; malonyl-coenzyme A; carnitine palmitoyltransferase; medium-chain fatty acids; endurance training; muscle
 |
INTRODUCTION |
ONE OF THE HALLMARK ADAPTATIONS to endurance training
is a decrease in carbohydrate utilization and an increase in fatty acid oxidation during exercise of the same absolute intensity after training
(9, 11). The glucose-fatty acid cycle hypothesis [i.e., increased
fatty acid oxidation suppressing carbohydrate utilization by inhibition
of key enzymes of the glycolytic pathway, resulting in increased
glucose 6-phosphate (G-6-P)
concentration (18)] has been proposed to explain the adaptations
in substrate utilization with training (8). However, Jansson and
Kaijser (11) and, more recently, Coggan et al. (2) found that muscle G-6-P concentration was lower during
exercise in the trained state, indicating that the shift in substrate
utilization after training is unlikely to be explained by the
glucose-fatty acid cycle concept as proposed by Randle et al. (18).
Alternatively, the increase in fatty acid oxidation with endurance
training may be mediated by the decrease in carbohydrate utilization.
From work in vitro it has been suggested that increased pyruvate
availability increases malonyl-CoA formation, which in turn inhibits
carnitine palmitoyltransferase (CPT) I, thereby decreasing fatty acid
oxidation (16). Consistent with this hypothesis, evidence has recently
been provided that increased carbohydrate flux decreases fat oxidation
by inhibition of fatty acid entry into the mitochondria both at rest
(24) and during exercise (23). Because training reduces the rate of
carbohydrate flux during exercise, it has been hypothesized (3) that
the difference in fatty acid oxidation during exercise of the same
absolute intensity in the trained vs. the untrained state may be due to
accelerated long-chain fatty acid entry into the mitochondria.
We have investigated the regulation of fatty acid oxidation during
exercise on a cycle ergometer at an oxygen consumption (
O2) of ~2 l/min in five
sedentary men and five well-trained cyclists.
[1-13C]oleate and
[1-14C]octanoate were
infused to trace the metabolism of the long- (LCFA) and medium-chain
fatty acids (MCFA), respectively. Octanoate, unlike oleate, freely
enters the cell and crosses the inner mitochondrial membrane; hence, if
fatty acid oxidation is higher in the trained state due to increased
mitochondrial LCFA uptake, then oleate oxidation and the percentage of
[1-13C]oleate taken up
by tissues that is oxidized should be higher in the trained group.
Octanoate oxidation and the percentage of [1-14C]octanoate
uptake that is oxidized, however, would not be expected to differ
between the two groups.
 |
METHODS |
Volunteers.
Five sedentary male volunteers and five endurance-trained cyclists
participated in this study. Volunteer characteristics are presented in
Table 1. All volunteers were healthy, as
indicated by comprehensive history, physical examination, and standard
blood and urine tests, and they consented to participate in this study, which was approved by the Institutional Review Board and the General Clinical Research Center of the University of Texas Medical Branch at
Galveston.
Experimental design.
All experiments were performed in the morning after the volunteers had
fasted overnight (i.e., 12 h). Trained volunteers were instructed to
limit the duration (to <45 min) as well as the intensity of their
final training bout, which was performed 24 h before the study. Teflon
catheters were placed percutaneously into an antecubital vein for
isotope infusion and into a contralateral dorsal hand vein, which was
heated, for sampling of arterialized venous blood. After catheter
placement, each volunteer sat quietly on a cycle ergometer for
15-30 min. Blood and breath samples were then obtained for the
determination of background enrichments, after which the sedentary
volunteer exercised for 30 min and the trained volunteer for 60 min at
a
O2 of ~2.0
l/min. This represented ~80 and 40% of peak
O2
(
O2 peak)
for the sedentary and trained volunteers, respectively. At the
beginning of exercise, infusions of
[1-14C]octanoate
(prime = 16.0 nCi/kg, constant infusion = 1.0 nCi · kg
1 · min
1)
and [1-13C]oleate (no
prime, constant infusion = 0.15 µmol · kg
1 · min
1)
were started and continued for the duration of the exercise by use of
syringe pumps (Harvard Apparatus, Natick, MA). The bicarbonate pools
were primed via bolus infusion of
NaH14CO3
(40 nCi/kg) and
NaH13CO3
(7.0 µmol/kg) at the beginning of the study. In the sedentary group
only, a lipid emulsion (0.5 ml · kg
1 · h
1)
was infused together with heparin (bolus of 7.0 U/kg; continuous infusion of 7.0 U · kg
1 · h
1)
to prevent the expected decline in plasma free fatty acid (FFA) concentration observed during strenuous exercise (20). It was not
necessary to infuse MCFA during exercise in either group, because there
is virtually no octanoate in plasma, and thus the specific activity
(SA) of plasma octanoate should be the same as that of the octanoate
infusate in both groups.
Blood samples were obtained before tracer infusion and every 5 min
during the infusion for determination of plasma oleate enrichment and
oleate, total plasma FFA, glucose, and lactate concentrations. Breath
samples for determination of
13CO2
carbon enrichment and
14CO2
carbon SA were collected before tracer infusion and every 5 min during
the study. Indirect calorimetry was performed during the last 10 min
of each study to determine
O2 and
CO2 production (
CO2).
On separate occasions the volunteers repeated the experimental protocol
but without isotope infusion. Only breath samples were collected during
these tests; these were used to quantify changes in breath
CO2 carbon enrichment due to the
shift in substrate mix observed in the transition from rest to exercise
(27).
Materials.
[1-13C]oleate, 99%
enriched, was obtained from MSD Isotopes (Montreal, Canada),
[1-14C]octanoate from
Du Pont (Boston, MA), human albumin (5%) from Baxter Healthcare
(Glendale, CA), the lipid emulsion [Intralipid, 20%, containing
linoleic (50%), oleic (26%), palmitic (10%), linolenic (9%), and
stearic (3.5%) acids] from Kabi (Clayton, NC), and heparin from
Elkins Sinn, Cherry Hill, NJ.
Assays.
Expired air was collected in 3-liter anesthesia bags, and
14CO2
carbon SA was determined using a liquid scintillation counter, as
previously described (21). For determination of breath
CO2 carbon enrichment, 10 ml of
expired air were injected into evacuated tubes, and the
13CO2-to-12CO2
ratio (tracer-to-tracee ratio; enrichment) was determined using isotope
ratio mass spectrometry (SIRA VG Isotech, Cheshire, UK) as previously
described (21).
Blood samples (6 ml) were collected into prechilled tubes containing
120 µl of 0.2 M ethylene glycol-bis(
-aminoethyl
ether)-N,N,N',N'-tetraacetic acid to inhibit in vitro lipolysis as well as clotting, and plasma was
immediately separated by centrifugation and frozen until further processing. Plasma oleate carbon enrichment was determined by following
previously described procedures (26). Briefly, FFA were extracted from
plasma, isolated by thin-layer chromatography, and converted to their
methyl esters. The isotopic enrichment of oleate carbon was determined
by gas chromatography-mass spectrometry (GC-MS; Hewlett-Packard 5890 Series II, Palo Alto, CA) by selectively monitoring the mass-to-charge
ratio of ions 296 and 297 (26).
Plasma glucose and lactate concentrations were determined on a 2300 STAT analyzer (Yellow Springs Instruments, Yellow Springs, OH). Plasma
oleate and total FFA concentrations were determined by GC
(Hewlett-Packard 5890) with heptadecanoic acid as internal standard.
Calculations.
Plasma oleate and breath CO2
carbon enrichment
(13C-to-12C
ratio) and SA
(14C-to-12C
ratio) reached plateau over at least the last 15 min of exercise (Figs.
1 and 2,
respectively). The average enrichment values during the last 10 min of
exercise were used for the calculation of substrate kinetics and
oxidation. Substrate oxidation calculated at 20-30 min was not
different from that calculated at 50-60 min of exercise at ~40%
O2 peak
in the trained group. Therefore, we compared substrate oxidation values
calculated for the last 10 min of exercise in the sedentary and trained
groups.

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Fig. 1.
Plasma oleate carbon enrichment
(13C-to-12C
ratio) in sedentary (A) and
endurance-trained volunteers (B)
during the last 25 min of cycle ergometer exercise at an oxygen
consumption ( O2) of ~2.0
l/min. Values (means ± SE for 5 volunteers) of the last 10 min were
used for calculation of oleate kinetics.
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Fig. 2.
Breath CO2 carbon specific
activity
(14C-to-12C
ratio from
[1-14C]octanoate
infusion; A) and enrichment
(13C-to-12C
ratio from
[1-13C]oleate
infusion; B) in sedentary and
endurance-trained volunteers during the last 25 min of cycle ergometer
exercise at a O2 of ~2.0
l/min. Values (means ± SE for 5 volunteers) of the last 10 min were
used for calculation of substrate oxidation and percent uptake
oxidized.
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|
Carbohydrate and total fatty acid oxidation rates were calculated from
indirect calorimetry by use of stoichiometric equations (5).
O2 and
CO2
values were the average over the last 10 min of each study. Fatty acid
oxidation was determined by converting the rate of triacylglycerol (TG)
oxidation
(g · kg
1 · min
1)
to its molar equivalent, with the assumption of the average molecular
weight of TG to be 860 g/mol (5), and multiplying the molar rate of TG
oxidation by three because each molecule contains three moles of fatty
acids.
The rate of appearance (Ra) of
oleate in plasma, which under steady-state conditions is equal to the
rate of disappearance (Rd), was
calculated as
where F is the
oleate tracer infusion rate, and
Eo is the oleate carbon enrichment
in plasma. FFA Ra was derived by
dividing the Ra oleate by the
fractional contribution of oleate to the total FFA concentration, as
determined by GC.
The rates of
13CO2
and
14CO2
excretion, resulting from the oxidation of
[1-13C]oleate and
[1-14C]octanoate,
respectively, were calculated as
where
ECO2 is
breath CO2 carbon enrichment, and
ECO2 bkg
is breath
CO2 carbon enrichment obtained the
day that no tracers were used, representing the change in carbon
enrichment due to the shift in oxidized substrate mix resulting from
the transition from rest to exercise (27).
The absolute rates of
[1-13C]oleate and
[1-14C]octanoate
oxidation
(µmol · kg
1 · min
1)
were then calculated as
where
0.85 is the acetate correction factor for a
O2 of 2 l/min estimated
from Ref. 22. The acetate correction factor is preferable to the
bicarbonate correction factor because, unlike the bicarbonate
correction factor, the acetate correction factor better accounts for
label fixation (21, 22). The SA of the octanoate infusion mixture was
used as the octanoate enrichment in plasma, because there is virtually
no octanoate in plasma.
Plasma fatty acid oxidation was determined by dividing the rate of
oxidation of oleate by the fractional contribution of oleate to the
total FFA concentration, as determined by GC. The rate of oxidation of
fatty acids oxidized directly without first passing through the plasma
pool (so-called "intramuscular" or "nonplasma" fatty acids)
was calculated as
The percentage of oleate and octanoate tracer that was taken up
by tissues (i.e., cleared from the circulation) and oxidized was
calculated as
Statistical analysis.
Differences between the two groups were identified using an unpaired
t-test. Statistical significance was
set at P < 0.05.
 |
RESULTS |
Plasma substrate concentrations are presented in Table
2 as the average of the last 10 min of
exercise. By infusing lipids and heparin in the sedentary volunteers,
we were able to maintain similar plasma oleate and total FFA
concentrations in the two groups. Plasma glucose concentration was also
similar in the two groups; however, plasma lactate concentration was
significantly higher in the sedentary volunteers
(P < 0.05). Similarly, carbohydrate oxidation was significantly higher in the sedentary group (196 ± 9 vs. 102 ± 17 µmol · kg
1 · min
1,
P < 0.05).
The Ra of oleate in plasma was
similar in the two groups, as was the
Ra of total FFA (Table
3). Oleate oxidation (Fig.
3) and plasma fatty acid oxidation (tracer
methodology; Table 3) were significantly higher in the trained group,
whereas octanoate oxidation rate was not different in the two groups
(1.2e
05 ± 9.3e
07 vs.
8.7e
06 ± 2.8e
07
µmol · kg
1 · min
1
in the sedentary and trained volunteers, respectively). Total fatty
acid oxidation, calculated using indirect calorimetry and representing
the sum of plasma derived and nonplasma fatty acids (intramuscular, fatty acids that are oxidized without
first entering the plasma), was 16.7 ± 4.4 µmol · kg
1 · min
1
in the trained and 0 µmol · kg
1 · min
1
in the untrained. Given that there was significant plasma fatty acid
oxidation even in the untrained volunteers, as measured using the
labeled oleate (Fig. 3), indirect calorimetry significantly underestimated fat oxidation in this group of untrained volunteers.

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Fig. 3.
Plasma oleate oxidation during cycle ergometer exercise at a
O2 of ~2.0 l/min
in sedentary and endurance-trained volunteers. Lipids and heparin were
infused in the sedentary group to maintain plasma free fatty acid
concentration constant in the 2 groups. Values are means ± SE for 5 volunteers. * P < 0.05 vs.
sedentary.
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|
The percent
[1-13C]oleate uptake
that was oxidized was higher in the trained
(P < 0.05; Fig.
4) group, whereas the percent
[1-14C]octanoate
uptake that was oxidized was similar in the two groups (Fig. 4). The
ratio of percent
[1-13C]oleate to
percent
[1-14C]octanoate
oxidized was also higher in the trained group (Fig. 5), suggesting that fatty acid oxidation is
higher in the trained partly because of accelerated entry of fatty
acids into the mitochondria. Interestingly, unlike the sedentary group,
in the trained group the ratio of percent
[1-13C]oleate to
percent
[1-14C]octanoate
oxidized was not significantly different from one, suggesting that
mitochondrial fatty acid uptake is not the rate-limiting step in
endurance-trained cyclists exercising at a
O2 of ~2 l/min.

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Fig. 4.
Percentage of oleate and octanoate tracer taken up by tissues and
oxidized during cycle ergometer exercise at a
O2 of ~2.0 l/min in
sedentary and endurance-trained volunteers. Values are means ± SE
for 5 volunteers. * P < 0.05 vs. sedentary.
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Fig. 5.
Ratio of percent oleate uptake oxidized to percent octanoate taken up
and oxidized during cycle ergometer exercise at a
O2 of ~2.0 l/min in
sedentary and endurance-trained volunteers. A ratio significantly
different from unity suggests that mitochondrial fatty acid uptake is
rate limiting for fatty acid oxidation. Values are means ± SE for 5 volunteers.
* P < 0.05 vs. unity.
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 |
DISCUSSION |
Using isotopically labeled LCFA and MCFA, we have provided evidence
that mitochondrial fatty acid uptake is rate limiting for fatty acid
oxidation during high-intensity exercise in sedentary individuals. In
contrast, during exercise of the same absolute intensity in trained
subjects, fatty acid entry into the mitochondria was enhanced and was
apparently no longer limiting for fatty acid oxidation. These findings
suggest that, during exercise of the same intensity, fat oxidation is
higher in endurance-trained vs. sedentary individuals in part because
of accelerated fatty acid entry into the mitochondria.
The comparison of oleate to octanoate oxidation requires the assumption
that the main difference between the fate of the two tracers is the
need for oleate to utilize CPT for transport across the mitochondrial
membrane. McGarry and Foster (15) tested this assumption by comparing
relative rates of oxidation of octanoate, oleate, and
(
)-octanoylcarnitine in perfused rat livers.
(
)-Octanoylcarnitine, in contrast to octanoate, is transported
across the mitochondrial membrane utilizing CPT but enters the same
-oxidation pathway as octanoate once inside the mitochondria. It was
found that the relative rate of (
)-octanoylcarnitine oxidation
followed that observed for oleate rather than octanoate in livers from
fed and fasted rats, suggesting that the main difference in the
oxidation of oleate and octanoate is the need for oleate to utilize CPT I for transport across the mitochondrial membrane. However, there is
still the possibility that LCFA and MCFA may also differ in their mode
of transport across the sarcolemmal membrane. Unlike MCFA, which are
thought to be able to diffuse across the membrane, LCFA may require a
transport system to gain access into cells (1, 10). Therefore, the
increase in the capacity of the trained volunteers to oxidize LCFA
could also be interpreted as reflecting a training-induced increase of
the capacity of muscle for uptake of fatty acids. Whereas this is
certainly a possibility that cannot be excluded from our data, it could
not explain the increased oxidation of fatty acids derived from
triacylglycerols stored inside the cell (intramuscular
triacylglycerols) that was observed in the trained volunteers (Table
3).
The relative concentration of various fatty acids in plasma may affect
their kinetics and oxidation. To prevent the effect of different
concentrations of oleate on oleate uptake and oxidation, we infused
lipids and heparin during exercise in the sedentary group to increase
oleate availability to the same level as in the trained group. This was
necessary because peripheral lipolytic rate decreases significantly
during high-intensity exercise (20). By matching oleate availability in
the sedentary and trained groups, we ensured a valid comparison for
oleate oxidation between them. On the other hand, oleate and octanoate
concentrations were significantly different, which raises the
possibility that the observed differences in their kinetics and
oxidation may have been due to differences in their relative
concentrations. We have previously tested this possibility (23). We
increased the Ra of octanoate in
plasma during exercise at 40 and 80%
O2 peak
by exogenous infusion of unlabeled octanoate to match the
Ra of oleate. In these studies we
did not observe any significant changes in the percent octanoate tracer
oxidized between the "low" and "high" octanoate
availability experiments, suggesting that the observed differences
between octanoate and oleate tracer oxidation are not due to
differences in their relative concentrations (23).
The fact that the sedentary volunteers oxidized a greater percentage of
octanoate than oleate during high-intensity exercise supports the
concept that flux through CPT I may be rate limiting for fat oxidation
during exercise when the rate of carbohydrate utilization is very high
(4, 23). However, this did not appear to be true in trained volunteers
exercising at the same absolute intensity. In these subjects, the
percentage of oleate uptake that was oxidized was similar to that of
octanoate, such that the ratio of their relative rates of oxidation did
not differ significantly from unity. Thus some factor other than
mitochondrial fatty acid uptake was apparently rate limiting for fat
oxidation under these conditions in the trained volunteers. Possibly,
during the early stages of low-intensity exercise, fat oxidation is
limited by the rate of lipolysis and thus fatty acid availability.
The exact mechanism explaining the higher fatty acid oxidation in the
trained volunteers cannot be determined from the present study.
However, several possibilities can be suggested. It is well established
that activated LCFA must bind to carnitine, a reaction catalyzed by the
enzyme CPT I, to gain access into the mitochondrial matrix (6). The
product of this reaction, fatty acyl-carnitine, is transported across
the inner mitochondrial membrane via the carnitine-acylcarnitine
translocase mechanism (17). Studies in vitro (16) and in vivo (23, 24)
have suggested that accelerated carbohydrate flux inhibits CPT I,
possibly via malonyl-CoA (16), and, as a consequence, fatty acid uptake into the mitochondria and fatty acid oxidation decrease. Our data suggest that the increase in fat oxidation after training is at least
in part due to accelerated entry of fatty acids into the mitochondria.
This is perhaps mediated via increased CPT I activity as a consequence
of decreased carbohydrate flux. Alternatively, it is well established
that endurance training increases the number of mitochondria in trained
muscles (see Ref. 8). Thus training may enhance fatty acid entry into
the mitochondria by increasing the number of mitochondria without any
change in CPT I activity per mitochondrion. Furthermore, chronic
increased fatty acid availability to the mitochondria, as is probably
the case in endurance training, may also increase CPT I [rat
hepatocytes (14)] and
-hydroxyl-CoA-dehydrogenase [human
vastus lateralis; (7)] activities, explaining the ability of the
trained volunteers to oxidize more fatty acids.
In the present study we found that 58 ± 3% and 76 ± 7%
(P < 0.05) of oleate tracer were
oxidized in the sedentary and trained volunteers, respectively. Martin
et al. (13) did not see any difference in the percentage of LCFA tracer
oxidized before and after 12 wk of endurance training. Similarly,
Kanaley et al. (12) did not observe any difference between marathon
runners and moderately trained runners in the percentage of fatty acid
uptake oxidized. In the above mentioned studies (12, 13), the
differences in oxidative capacity between the two groups [i.e.,
before and after training (13) and marathoners vs. moderately trained
runners (12)] may not have been as large as in the present study.
It is possible that a difference in the percentage fatty acid uptake oxidized between trained and untrained persons may only become obvious,
or measurable, when the difference in oxidative capacity is very large,
as was probably the case in our two groups of volunteers.
There was a clear discrepancy between fatty acid oxidation calculated
using indirect calorimetry and tracer methodology during exercise in
the untrained group (Table 3). Indirect calorimetry suggested that
there was virtually no fatty acid oxidation during exercise, whereas
tracer estimates indicated that fatty acid oxidation contributed
significantly to energy production. High-intensity exercise is often
associated with a progressive increase in plasma lactate concentration,
progressive hyperventilation, and a decrease in the bicarbonate pool as
reflected in plasma bicarbonate concentrations (25). Under such
conditions indirect calorimetry may not be valid in estimating
substrate oxidation, because changes in the bicarbonate pool preclude
reliable measurements of tissue
CO2 by breath
CO2 analyses. On the other hand,
if lactate concentration increases in the initial phase of the exercise
but remains stable subsequently, as is the case with highly trained
cyclists exercising at ~80% maximal aerobic capacity (19), indirect
calorimetry may still be valid in estimating whole body fatty acid
oxidation (19).
Because muscle glycogen concentrations were not measured in this study,
it is possible that the two groups differ in their preexercise glycogen
stores (lower in trained), which could potentially affect the
interpretation of the findings of the present study. However, it seems
unlikely that potential differences in preexercise glycogen stores have
significantly influenced the pattern of glycogen use in these two
groups, because on the basis of the literature, the trained
volunteers exercising at 40%
O2 peak
used significantly less muscle glycogen than the sedentary volunteers
exercising at 80%
O2 peak.
However, it is still possible that the observed differences in fatty
acid oxidation between the two groups reflect genetic variation in
physiological characteristics of the subjects, such as fiber type,
percent body fat, or hormonal responses. As a cross-sectional design,
the present study shares all the limitations inherent in this type of
research design.
In summary, the results of the present study suggest that endurance
training may increase fat oxidation during exercise in part by
enhancing fatty acid entry into the mitochondria. This may be due to
decreased carbohydrate flux and thus increased CPT I activity per
mitochondrion, or simply to increased mitochondrial number and thus
increased total CPT I. Furthermore, our data suggest that in untrained
human volunteers exercising at a
O2 of 2 l/min, mitochondrial
fatty acid uptake is one factor limiting the rate of fat oxidation.
However, when trained volunteers exercise at the same absolute
intensity, fatty acid uptake by the mitochondria does not appear to be
limiting fat oxidation.
 |
ACKNOWLEDGEMENTS |
The authors gratefully appreciate the help of the nursing staff of
the General Clinical Research Center (GCRC) in the performance of the
experiments.
 |
FOOTNOTES |
This work was supported by National Institute of Diabetes and Digestive
and Kidney Diseases Grants DK-34817 and DK-46017, GCRC Grant 00073, and
Shriners Hospital Grant 15849.
Address for reprint requests: L. S. Sidossis, Metabolism Unit, Shriners
Burns Institute, Univ. of Texas Medical Branch, Galveston, TX 77550.
Received 22 July 1997; accepted in final form 25 November 1997.
 |
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