REVIEW ARTICLE Sports Med 2001; 31 (1): 47-59

0112-1642/01/0001-0047/$22.00/0

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Alterations in Energy Metabolism

During Exercise and Heat Stress
Mark A. Febbraio
Exercise Physiology & Metabolism Laboratory, Department of Physiology,
University of Melbourne, Parkville, Victoria, Australia

Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
1. Metabolic Alterations During Exercise and Heat Stress . . . . . . . . . . . . . . . . . . . . . . . . . 48
1.1 Substrate Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
1.1.1 Carbohydrate Utilisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
1.1.2 Lipid and Protein Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
1.2 Glucose Availability and Requirement During Exercise and Heat Stress . . . . . . . . . . . . . 51
1.3 Muscle Energy Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
2. Mechanisms Responsible for Alterations in Exercise Metabolism . . . . . . . . . . . . . . . . . . . . 52
2.1 Reductions in Contracting Skeletal Muscle Blood Flow . . . . . . . . . . . . . . . . . . . . . . 52
2.2 Alterations in Neuromuscular Recruitment Pattern . . . . . . . . . . . . . . . . . . . . . . . . . 53
2.3 Direct Temperature Effect on Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
2.4 Effects of Catecholamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

Abstract Much of the research that has examined the interaction between metabolism
and exercise has been conducted in comfortable ambient conditions. It is clear,
however, that environmental temperature, particularly extreme heat, is a major
practical issue one must consider when examining muscle energy metabolism.
When exercise is conducted in very high ambient temperatures, the gradient for
heat dissipation is significantly reduced which results in changes to thermoregu-
latory mechanisms designed to promote body heat loss. This can ultimately im-
pact upon hormonal and metabolic responses to exercise which act to alter substrate
utilisation. In general, the literature examining metabolic responses to exercise
and heat stress has demonstrated a shift towards increased carbohydrate use and
decreased fat use. Although glucose production appears to be augmented during
exercise in the heat, glucose disposal and utilisation appears to be unaltered. In
contrast, glycogen use has been consistently demonstrated to be augmented dur-
ing exercise in the heat. This increase in glycogenolysis is observed via both
aerobic and anaerobic pathways. Although several hypotheses have been pro-
posed as mechanisms for the substrate shift towards greater carbohydrate meta-
bolism during exercise and heat stress, recent work suggests that an augmented
sympatho-adrenal response and intramuscular temperature may be responsible
for such a phenomenon.
48
The combination of exercise and heat stress in-
creases the cardiovascular and thermoregulatory
strain of humans because of the requirement to
send blood to the skin in these conditions. Since the
cardiovascular and thermoregulatory systems are
thought to be primarily responsible for the decrease
in exercise performance observed in hot environ-
ments, most of the research which examines the phys-
iological responses to exercise and thermal stress
has focused on these systems (for review see refer-
ences[1-5]). In contrast, before the 1990s there were
few studies which comprehensively examined the
effect of exercise in the heat on metabolic processes
and the mechanisms which may be responsible for
any observed changes. However, since this time
research in this area has increased. This review ex-
amines recent advances in the effects of heat stress
on exercise metabolism and the underlying mech-
anisms responsible for the metabolic changes which
occur.
1. Metabolic Alterations During
Exercise and Heat Stress
1.1 Substrate Metabolism
1.1.1 Carbohydrate Utilisation
Fink et al.[6] were the first to demonstrate that en-
vironmental temperature affects intramuscular sub-
strate utilisation during submaximal exercise. They
observed that 60 minutes of intermittent exercise
at 41C increased intramuscular glycogen use, with
a concomitant decrease in triglyceride use, compared
with exercise at 9C. Since this initial study, others
have examined the effect of exogenous heat stress
on substrate use in greater detail. Consistent with the
results from Fink et al.[6] others[7-9] have observed
an augmented intramuscular carbohydrate utilisa-
tion when comparing 40 minutes of exercise at 70%
.
of maximal oxygen uptake (VO2max) in the heat
with that in a cooler environment. In addition, when
the rise in body temperature is attenuated by heat
acclimation,[7,10-12] by preventing dehydration,[13,14]
by reducing the ambient temperature,[15,16] or by pro-
viding external cooling,[17] muscle glycogenolytic
rate and/or carbohydrate oxidation is/are reduced. In
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Febbraio
must be noted, however, that several studies[12,18-21]
have not observed increased intramuscular glyco-
gen utilisation during exercise and heat stress. A
careful examination of the methodologies employed
and the circumstances in which the data were col-
lected may explain why some, but not all, studies
demonstrated an effect of heat stress on glycogeno-
lytic rate during exercise.
Exercise in itself results in relative hyperther-
mia.[15] Hence, the difference in body core temper-
ature when comparing experimental conditions must
be of sufficient magnitude to result in altered me-
tabolic responses. Factors such as the acclimation
status of the subject population, the magnitude of
difference in the ambient temperature and the pre-
sence or absence of circulating air will all affect
body core temperature responses. Although Yaspel-
kis et al.[20] observed no differences in glycogenol-
ysis when comparing exercise in the heat with that
in a cooler environment, the ambient temperature
difference when comparing the 2 experimental con-
ditions was approximately 10C and the subject
population was heat acclimatised. As a result, the
largest difference in body core temperature at any
point when comparing the 2 experimental trials was
0.4C, a difference unlikely to have major physio-
logical ramifications.
It is also important to note that the rate of gly-
cogenolysis during submaximal exercise is largely
influenced by pre-exercise glycogen levels.[22-24] It
is not surprising, therefore, that in studies where pre-
exercise glycogen levels were higher before exercise
in cooler, relative to warmer, experimental conditions
no differences were observed in intramuscular glyco-
genolysis.[19,21] Young and co-workers[21] had 2 groups
of participants, a hot water training group (HWT)
and cold water training group (CWT), perform 60
.
minutes of exercise at 60% VO2max in hot and cold
water, before and after training. In this study, pre-
exercise glycogen content was higher before exercise
in the cold water in the CWT group. As a result, more
glycogen was utilised in this trial. However, in the
HWT group before training (when pre-exercise gly-
cogen content was similar when comparing exer-
cise in the hot with that in the cold water), the glyco-
Sports Med 2001; 31 (1)
Energy Metabolism in Exercise and Heat Stress
genolytic rate although not statistically different
during exercise was approximately 25% higher in
the hot trial. In the study by Young et al.,[12] muscle
glycogen content was not different when compar-
ing exercise in the heat with that in a cooler envi-
ronment. Nonetheless, intramuscular lactate accu-
mulation was elevated during exercise in the hot
environment suggesting that anaerobic glycolysis
was accelerated with exercise under these condi-
tions.
Recently, Maxwell et al.[18] demonstrated no dif-
ference in the rate of glycogenolysis when compar-
ing maximal exercise in the heat with that in a cooler
environment. As suggested by these authors, the
supramaximal nature of the exercise may have in-
creased the energy turnover to a level where heat
stress was rendered unimportant. Indeed muscle lac-
tate accumulation in both trials was >100 mmol/kg dry
mass. It appears, therefore, that if exercise in the
heat is submaximal in nature and a marked (>0.5C)
increase in body core temperature is observed, in-
tramuscular carbohydrate utilisation is indeed aug-
mented. If, however, body temperature is not mark-
edly influenced by exercise and heat stress, it is
unlikely that metabolic differences will be observed
during exercise and heat stress.
The increase in glycogen utilisation observed
during exercise and heat stress appears to involve
both oxidative and nonoxidative energy pathways.
Muscle lactate accumulation is augmented in both
humans [7,8,12-14,16] and dogs[17] during exercise and
heat stress. While these data suggest that flux through
anaerobic glycolysis is augmented during exercise
and heat stress, they do not allow for precise meas-
urements of glycolytic rates. There have been few
studies which have examined lactate efflux from
contracting skeletal muscle and uptake by other
organs and tissues during exercise and heat stress.
Nielsen et al.[19] demonstrated that neither arterio-
venous lactate level differences nor lactate release
rates from contracting skeletal muscle were differ-
ent when comparing exercise in the heat with that
in a cooler environment, although these data are
difficult to interpret since 60 minutes of exercise
in the heat followed 30 minutes of exercise in a
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49
thermoneutral environment, rendering the exper-
iment noncounterbalanced. However, researchers
from the same laboratory have recently demonstrated
a higher postexercise muscle lactate content in the
presence of an augmented lactate release, when com-
paring exercise and dehydration-induced hyperther-
mia with similar exercise in a euhydrated state.[13]
These recent data support the classical work from
Rowell and colleagues[25] in the 1960s who observed
that, during exercise in the heat, the magnitude of
the increase in arterial lactate levels could not be
accounted for by lactate removal. Taken together,
these data suggest that exercise in the heat increases
intramuscular lactate production, although the reg-
ulation of glycolysis during exercise and heat stress
warrants further investigation.
The consistent observation of an increased re-
spiratory exchange ratio (RER)[7-9,12,26] suggests that
carbohydrate, in particular glycogen, is also ox-
idised to a greater extent during exercise and heat
stress, possibly at the expense of lipid oxidation.
Recent evidence from both our research group[9]
and others[13] supported this hypothesis. Using an
isotopic tracer method we have demonstrated that
glucose disappearance (Rd) was not different when
comparing exercise at 40C with that at 20C. In
contrast, estimated rates of carbohydrate oxidation
uptake were higher in the heat. If we assume that
the Rd glucose was fully oxidised within contract-
ing skeletal muscle, the calculated intramuscular
glycogen oxidation was higher in the 40C trial
than in the 20C trial (fig. 1). Likewise, Gonzalez-
Alonso et al.[13] have demonstrated that contracting
limb respiratory quotient (RQ) was higher when com-
paring exercise and dehydration-induced hyper-
thermia with similar exercise in a euhydrated state.
These authors observed no difference in glucose to
contracting muscle as measured by arteriovenous
difference (fig. 1),[13] also suggesting that glycogen
oxidation was augmented. The combined results
suggest that flux through the pyruvate dehydroge-
nase (PDH) pathway is up-regulated during exer-
cise and heat stress because some of the pyruvate
formed during exercise is being oxidised. Whether
Sports Med 2001; 31 (1)
50 Febbraio

a b exercise in the heat compared with similar exercise

Glucose Fat in a cooler environment, although as previously dis-
Other carbohydrate Carbohydrate
cussed, the noncounterbalanced design adopted by
Carbohydrate oxidation (mmol/kg/min)

10 250
* Total leg substrate oxidation (g) these researchers was likely to have played a sig-
* nificant role in the metabolic measurements. In con-
200
7.5
trast, Gonzalez-Alonso et al.[13] observed a lower
150 FFA uptake during the latter stages of exercise with
5
dehydration-induced hyperthermia, when compared
100
with a euhydrated trial in the heat. Hence, based on
2.5 RQ and FFA flux across the contracting limb, total
50
* leg lipid oxidation was lower during dehydration-
0 0 induced hyperthermia,[13] a result consistent with
20 40 DE CON
the earlier observations of Fink et al.[6] It appears,
Temperature (C)
therefore, that exercise and acute heat stress results
Fig. 1. (a) Carbohydrate oxidation during exercise in the heat in an increase in intramuscular glycogen use via
(40C) and cool (20C);[9] and (b) substrate oxidation during
exercise in the heat in the presence (DE) or absence (CON) of
both oxidative and nonoxidative energy pathways.
dehydration.[13] Values are means [(a) n = 6; (b) n = 7]. * indicates The increase in lactate accumulation in both con-
difference (p < 0.05) (a) when comparing oxidation of other car- tracting muscle and plasma results from net intra-
bohydrates between trials; and (b) when comparing fat and car-
bohydrate oxidation between trials. muscular glycogenolysis and not from increased
uptake and oxidation of circulating glucose.
The effect of exercise and heat stress on protein
PDH activity (PDHa) is increased during exercise metabolism has not been directly measured because
in the heat has not, to date, been investigated. of the minimal contribution of protein to total energy
turnover and/or the difficulty in measuring protein
1.1.2 Lipid and Protein Metabolism turnover during exercise. However, there is indirect
There are few studies which have examined lipid evidence which suggests that protein catabolism may
metabolism during exercise and heat stress. Plasma be increased during such exercise. Work from our
free fatty acid (FFA) levels have been consistently laboratory has observed increased intramuscular
observed to be unaltered by exercise and thermal ammonia (NH3) accumulation in both endurance
stress.[6,19,20] However, plasma FFA levels only re-
trained[8] and untrained[28] humans. Although a major
flect a balance between whole body lipolysis and
pathway for NH3 production during exercise is via
FFA uptake by other tissues and organs during ex-
the deamination of adenosine 5-monophosphate
ercise. Of note, although Fink et al.[6] observed sim-
(AMP) to form NH3 and inosine 5-monophosphate
ilar plasma FFA levels when comparing exercise
in the heat with that in a cooler environment, they (IMP), NH3 can also be formed in skeletal muscle
also demonstrated that intramuscular triacylgly- from the oxidation of branched chain amino acids
cerol utilisation was reduced during exercise at 41C. (BCAA).[29] During our more recent study,[8] the
There have been no subsequent attempts to mea- augmented NH3 accumulation was observed in the
sure intramuscular triacylglycerol utilisation in hu- absence of any difference in IMP accumulation. In
man skeletal muscle during exercise and heat stress, addition, the exercise-induced increase in NH3 dur-
a fact most likely attributable to the high variability ing the hotter experimental condition was 5-fold
in current analytical techniques.[27] higher than the accumulation of IMP (fig. 2). Hence,
Only 2 studies have examined the effect of ex- these data suggest that protein degradation may be
ercise and heat stress on FFA uptake. Nielsen et increased during exercise in heat, although it must
al.[19] observed no change in FFA uptake during be noted that even if this were to be the case, the

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Energy Metabolism in Exercise and Heat Stress
1.5
NH3 20C *
NH3 40C
IMP 20C
IMP 40C
Concentration (mmol/kg)
*
1 cose isotope. Our data demonstrated that despite an
0.5
0
Before exercise After exercise
Fig. 2. Ammonia (NH3) and inosine 5-monophosphate (IMP)
levels before and after 40 minutes of exercise at 70% peak
oxygen uptake in the heat (40C) and cool (20C). Values are
means standard error (n = 12). * indicates difference (p < 0.05)
after exercise compared with before exercise; indicates differ-
ence (p < 0.05) at 40C compared with 20C.[8]
contribution of protein to total energy turnover
would be minimal.
1.2 Glucose Availability and Requirement
During Exercise and Heat Stress
Many studies have observed relative hypergly-
caemia during exercise and heat stress,[6,7,9,20,30]
which reflects an imbalance between glucose pro-
duction and utilisation. Rowell et al.[25] have dem-
onstrated that hepatic glucose production (HGP)
was augmented in heat-stressed humans using a
dye infusion technique. These data have recently
been confirmed using both isotopic tracer dilution
(fig. 3)[9] and arteriovenous balance[13] techniques.
The regulation of HGP during exercise involves a
complex interplay of neural and hormonal factors
and both feed-backand feed-forwardmechanisms
(for review see Kjr[31]). Hence, during submaxi-
mal exercise in comfortable ambient conditions,
euglycaemia is usually maintained by HGP and is
regulated to match the metabolic need for glucose.
Consequently, increasing circulating glucose lev-
els by exogenous feeding[32,33] or glucose infusion[34]
blunts the increase in HGP during exercise. How-
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51
ever, we have recently conducted an experiment
where individuals ingested either a placebo solu-
tion or a labelled isotopic glucose solution, while
being infused with an alternatively labelled glu-
increase in glucose appearance from the gastroin-
testinal tract and a concomitant increase in plasma
glucose, with glucose ingestion HGP was unaffected
(fig. 4).[35] The absence of effective feed-back reg-
ulation of HGP with carbohydrate ingestion high-
lights the powerful feed-forward control of thermal
stress.
1.3 Muscle Energy Metabolism
There are few studies which have examined the
effect of whole body heat stress on muscle energy
metabolism during exercise. A reduction in the in-
tramuscular content of adenosine triphosphate (ATP)
and phosphocreatine (PCR), and increases in aden-
osine 5-diphosphate (ADP) and AMP accumula-
tion have been observed during fatiguing submaxi-
mal exercise with heat stress in dogs.[17] While PCR
degradation is augmented during exercise and heat
stress in humans, total adenine nucleotide (TAN =
ATP + ADP + AMP) metabolism, IMP accumula-
1500
* 20C
40C
1000
Ra/Rd (mol/kg)
500
0
Ra Rd
Fig. 3. Total hepatic glucose production (HGP = Ra and glucose
uptake (Rd) during 40 minutes of exercise at 70% peak oxygen
uptake in the heat (40C) and cool (20C). Values are means
standard error (n = 6). * indicates difference (p < 0.05) from
20C.[9]
Sports Med 2001; 31 (1)
52 Febbraio

a With CHO ingestion 2. Mechanisms Responsible for

Without CHO ingestion Alterations in Exercise Metabolism
8
*
A number of possible mechanisms have been
Plasma glucose (mmol/L)

7 proposed to account for the shift towards increased

carbohydrate metabolism observed during some
studies.[4,12,17,36] These include: a reduction in ox-
6 ygen (O2) and substrate delivery and utilisation be-
cause of a reduced muscle blood flow during exer-
cise in the heat,[4] an alteration in neuromuscular
5
recruitment pattern favouring greater use of fast
rather than slow twitch fibres during exercise,[12,36]
a direct temperature effect on enzyme-mediated re-
4
0 10 20 30 40 50 60
action rates (the Q10 effect),[12,17] and the effect of
b increased circulating adrenaline levels.[10,20]
40

2.1 Reductions in Contracting Skeletal

Muscle Blood Flow
30
HGP (mol/kg/min)

It is clear that the increased demand for skin

20
10
0
0 10 20 30 40 50
Time (min)
Fig. 4. (a) Plasma glucose; and (b) hepatic glucose production
(HGP) during 60 minutes of exercise at 70% peak oxygen up-
take in 35C with or without the ingestion of carbohydrate (CHO).
Values are means standard error (n = 6). * indicates difference
(p < 0.05) when comparing trials (adapted from Angus et al.,[35]
with permission).
tion and the energy charge potential of the contract-
ing muscle is unaltered when comparing 40 min-
utes of exercise at 40C with similar exercise at
20C.[8] Whilst the variations observed when com-
paring these 2 studies may be related to species
differences, they may also be related to the impor-
tant fact that one protocol required the participants
to exercise to exhaustion, while the other was non-
fatiguing and of fixed duration.
circulation during exercise and heat stress is met
by an attenuated blood flow to some other organs.
Reductions in splanchnic,[25] hepatic,[37] renal[38]
and inactive skeletal muscle[39] blood flow occurs
during exercise and heat stress. However, many au-
thors[6,17,19,40,41] have also hypothesised that the skin
and active muscle compete for blood during exer-
60
cise in the heat because the cardiovascular demand
exceeds the pumping capacity of the heart.[40] Such
cardiovascular alterations may impact upon on me-
tabolism because it may reduce O2 availability and
cellular respiration. Whether or not contracting skel-
etal muscle blood flow is reduced is the subject of
some controversy.[19,42] In addition, if blood flow
is reduced during exercise and heat stress, it is un-
clear whether this leads to any modification in O2
extraction. Quantitative measures of contracting
muscle blood flow using radioactive microspheres
have demonstrated a reduced blood flow in heat
stressed, exercising sheep.[42] However, direct meas-
urements of active limb blood flow in humans us-
ing a thermodilution technique,[19,43-45] or active
muscle blood flow using plethysmography and dop-
pler flowmetry[46] have observed unaltered blood
flow during exercise and heat stress.

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Energy Metabolism in Exercise and Heat Stress
While species differences, such as mechanisms
for dissipating heat (panting versus sweating) and
hydrostatic pressures (4-legged vs 2-legged upright
exercise) are likely to account for the discrepancy
in the literature, it may be possible that in human
studies the degree of thermal circulatory stress was
not enough to compromise cardiac pumping capac-
ity. Recently, Gonzalez-Alonso et al.[47] observed
an attenuated contracting leg blood flow during ex-
ercise with dehydration and hyperthermia compared
with similar exercise with the maintenance of eu-
hydration. However, it must be noted that the im-
pairment of cardiovascular function is much higher
with the combination of dehydration and hyper-
thermia compared with hyperthermia alone, when
both these experimental conditions are expressed
relative to a control trial in a cooler environment.[48]
It appears therefore, that contracting limb blood
flow during exercise and heat stress may be re-
duced if the heat stress is marked. Whether or not
muscle metabolism is affected by reductions in blood
flow may depend upon whether a compensatory
extraction of O2 occurs.
Schumacker et al.[49] observed an increase in O2
extraction with hypovolaemia during hyperthermic
exercise in dogs. Although the combination of de-
hydration and hyperthermia during exercise results
in a 1.0 L/min decrease in contracting limb blood
flow when compared with similar exercise with the
maintenance of euhydration, leg O2 consumption
is unaffected.[47] Metabolic measures from this data
set demonstrated augmented intramuscular glyco-
gen utilisation and lactate accumulation with greater
heat stress.[13] Hence, the recent work from Gon-
zalez-Alonso et al.[13,47] suggests that even if con-
tracting muscle blood flow is reduced during exer-
cise and heat stress, arteriovenous O2 difference is
increased accordingly so that leg O2 availability is
not compromised. In addition, it appears that O2
availability is not the main factor mediating the
augmented glycogenolysis and lactate accumula-
tion during moderately intense exercise and heat
stress. This scenario does not rule out the possibil-
ity that a decrease in blood flow may influence
metabolic processes in an O2 independent manner.
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53
Clarke et al.[50] have clearly demonstrated that func-
tional vascular shunts exist in skeletal muscle such
that metabolism is altered via the change in the rate
of supply of nutrients and removal of products. The
importance of nutrient and non-nutrient flow dur-
ing exercise and heat stress is currently not known.
2.2 Alterations in Neuromuscular
Recruitment Pattern
A higher muscle lactate level has been observed
in the absence of any net alteration in glycogenol-
ysis during exercise in the heat.[12] In addition, these
investigators reported a significant correlation be-
tween the percentage of type II fibres and the dif-
ference in postexercise muscle lactate accumula-
tion when comparing exercise in a hot (49C) and
cool (21C) environment. These observations have
lead to the hypothesis that exercise in the heat re-
sults in a greater proportion of fast twitch fibre
recruitment or that fast twitch fibres are more sen-
sitive to temperature change compared with slow
twitch fibres.[12,36] We have tested this hypothesis
by performing similar correlations and by histo-
chemical analyses of glycogen use in type I and
type II fibres after 40 minutes of exercise in 40C
and 20C conditions.[7] In contrast with the find-
ings of Young et al.,[12] we did not observe any
correlation between lactate accumulation and fibre
type (r = 0.06; p > 0.05). Furthermore, in our study,
histochemical analyses suggested that type I fibres
were preferentially recruited irrespective of envi-
ronmental temperature (fig. 5); a neuromuscular
recruitment pattern which is consistent with pre-
vious observations during prolonged exercise in
thermoneutral conditions.[51]
2.3 Direct Temperature Effect on
Metabolism
During exercise intramuscular temperature
(Tmus) rises in proportion to the increase in work-
load[52] and the rise in Tmus is augmented during
exercise and thermal stress.[7-8,13,14,16] It has been
suggested that this rise in Tmus per se may act upon
key enzymes which ultimately alter exercise me-
tabolism.[17,41] The Q10 values commonly found
Sports Med 2001; 31 (1)
54
4 (Dark)
3 (Moderate)
2 (Light)
1 (Very light)
0 (Negative)
Type II fibres
40C
20C
Type I fibres
40C
* either heating pads or water perfused cuffs have
20C
0 25 50 75 100
Fibres (%)
Fig. 5. Histochemical analyses of glycogen content in muscle
stained with periodic acid Schiff (PAS) reagent in type I and type
II fibres after 40 minutes of exercise at 70% peak oxygen uptake
in the heat (40C) and cool (20C). Values are means standard
error (n = 6). * denotes difference (p < 0.05) in percentage of
dark stained fibres in 40C compared with 20C (adapted from
Febbraio et al.,[7] with permission).
for enzyme-mediated reactions are 2.0 to 3.0, that is,
for every 10C increase in temperature, a 2- to 3-
fold increase in enzyme reaction rate is observed.[53]
Since Tmus can be increased by up to approximately
2C when comparing exercise in the heat with that in
a cooler environment, enzyme reaction rates could
increase to approximately 30 to 40% under these
circumstances.
Few studies have attempted to directly elevate
Tmus and examine intramuscular metabolism. Ed-
wards et al.[54] examined the effect of increases in
Tmus on metabolism during isometric contractions
to fatigue. They demonstrated that both intramus-
cular glycogen utilisation and lactate accumulation
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Febbraio
were augmented during contractions following limb
immersion in a water bath at 44C when compared
with water bath temperatures of 12 and 26C. How-
ever, limb heating also resulted in an increase in core
temperature, whereas it was reduced in the 12C
trial. Because an elevated core temperature increases
plasma adrenaline levels,[7,9,13,16,55,56] which may
increase glycogenolysis during exercise,[57-59] this
may have influenced the results. It must also be
noted that the results from the study by Edwards et
al.[54] could not clearly determine whether elevated
Tmus per se plays a regulatory role in metabolic
processes during dynamic exercise coupled with
thermal stress, as isometric exercise has a lower
energy turnover compared with dynamic exercise.
We have recently conducted experiments where
been wrapped around the quadriceps muscles to ma-
nipulate Tmus. These methods have elevated Tmus
before and during intense[60] and submaximal[61]
exercise. Data from our initial study[60] demonstrated
that an elevation in muscle temperature increased
glycogenolysis and lactate accumulation in the ab-
sence of changes in body core temperature or plasma
catecholamine levels during 2 minutes of exercise
.
at a workload estimated to require 115% of VO2max.
In addition to the changes in glycogenolysis and
lactate formation, we also observed an augmented
decline in the TAN pool and increased IMP accu-
mulation. Although it was possible that the increase
in glycogenolysis and anaerobic glycolysis resulted
from a Q10 effect on glycogenolytic and glycolytic
processes, we could not rule out the possibility that
the decrease in TAN mediated these alterations. It
has been demonstrated that TAN degradation, in
particular increases in free ADP, results in alloste-
ric activation of key glycogenolytic and glycolytic
enzymes, namely phosphofructokinase (PFK)[62] and
phosphorylase,[63] thereby increasing flux through
glycolysis.
Our more recent study[61] adopted a protocol
which involved heating one leg and cooling the
other for 40 minutes before, and 20 minutes during,
.
exercise at 70% peak oxygen uptake (VO2peak) us-
ing water perfused cuffs. A difference in Tmus was
Sports Med 2001; 31 (1)
Energy Metabolism in Exercise and Heat Stress
observed after 40 minutes of pre-exercise treatment
and while this difference was reduced during the
20 minutes of exercise, it was nonetheless still sig-
nificantly different at the end of exercise. In addi-
tion to the higher Tmus observed in the heated leg
we also observed an augmented rate of glycogen
use, but no differences in high energy phosphagen
metabolism were noted when compared with the
cooled leg. Therefore, these data suggest that tem-
perature per se plays a regulatory role in intramus-
cular carbohydrate utilisation and appears to be
responsible, in part, for the frequently observed
increase in glycogen utilisation during exercise and
heat stress.
2.4 Effects of Catecholamines
It is well known that adrenaline secretion in-
creases during exercise (for review see Galbo[64]),
and that this increase is augmented with heat
stress.[7,9,13-16,19,55,56] Since glycogen phosphoryl-
ase activity is enhanced by -adrenergic receptor
stimulation,[65] any increase in circulating adrena-
line levels may result in a concomitant increase in
intramuscular glycogen utilisation. Although intra-
muscular glycogen utilisation often closely matches
the plasma adrenaline response during exercise and
heat stress,[7,14,15,48] this is not always the case.[19]
The effect of adrenaline on substrate metabolism
is a well studied, but nonetheless, complex phe-
nomenon. Studies conducted using animals have
demonstrated that epinephrine infusion increases
glycogen utilisation, during either voluntary sub-
maximal exercise or electrical stimulation in both
rats[65,66] and dogs.[67] In addition, removal of the
adrenal medulla[68] or -adrenergic receptor block-
ade[69] reduces glycogen use in these animals. Nev-
ertheless, studies in humans that have manipulated
plasma adrenaline levels via infusion have produced
conflicting results. Those which have demonstrated
that adrenaline enhances muscle glycogen use have
infused supraphysiological doses.[58,59]
In contrast, 2 studies have demonstrated that gly-
cogen use is not increased during intense dynamic[22]
or prolonged[70] exercise when epinephrine is in-
fused to mimic physiological increases during
Adis International Limited. All rights reserved.
55
exercise. It has been suggested that the effect of
adrenaline on glycogen phosphorylase is diminish-
ed by cellular regulatory mechanisms such as cal-
cium (Ca2+) release, substrate availability and post-
transformational allosteric modulators such as free
AMP and free IMP.[22,63,70] Although measures of
energy metabolites were not made by Wendling et
al.,[70] in the study by Chesley et al.,[22] exercise
.
was conducted at 85% VO2max which was likely to
have activated glycogen phosphorylase irrespec-
tive of adrenaline levels, via local factors such as
Ca2+ release from the sarcoplasmic reticulum and
post-transformational factors such as inorganic
phosphate (Pi), free ADP and free AMP levels. Ac-
cordingly, calculated levels of Pi, free ADP and free
AMP were markedly increased and similar when
comparing an epinephrine infusion with a control
trial.[22]
However, an increase in glycogen utilisation dur-
ing exercise and heat stress in trained men has been
observed in circumstances where there has been
little, if any, disruption to the intracellular milieu.[8]
This suggests that adrenaline may play a role in the
regulation of carbohydrate metabolism during pro-
longed exercise. It is also noteworthy that adrena-
line increases the glycogenolytic rate of type I but
not type II fibres,[57] and heat stress augments the
use of glycogen in type I fibres alone.
We have recently conducted a study where epi-
nephrine was infused into individuals at 20C to
mimic the sympatho-adrenal response observed at
40C.[71] The results demonstrated that adrenaline
does indeed increase muscle glycogen utilisation
and lactate formation in trained men exercising at
.
70% VO2peak (fig. 6), a circumstance which we have
previously shown[8] has no effect on the energy
charge potential or the ATP/ADP ratio in the con-
tracting muscle irrespective of the environmental
temperature. Hence, the results from this study[71]
suggest that the increase in muscle glycogen utilisa-
tion that occurs during exercise and heat stress is
mediated, in part, by an enhanced sympatho-adrenal
response.
Interestingly, RER is increased during exercise
and heat stress[7-9,12,26] or when epinephrine is in-
Sports Med 2001; 31 (1)
56 Febbraio

a c
3 With EPI
40C 600
20C Without EPI

Glycogen (mmol/kg dw)

Epinephrine (nmol/L)

500
2
* 400

* 300
1 *

200

0 100

b d
3
EPI 30
Muscle lactate (mmol/kg dw)

CON
Epinephrine (nmol/L)

2
20

#
* *
1 * 10
*

0 0
0 10 20 30 40 Before After
Time (min) exercise exercise

Fig. 6. (a) Plasma epinephrine (EPI) concentration during 40 minutes of exercise at 70% peak oxygen uptake in the heat (40C) and
cool (20C) [adapted from Febbraio et al.[9] with permission];[7] (b) plasma EPI concentration; (c) muscle glycogen use; and (d)
muscle lactate accumulation during 40 minutes of exercise at 70% peak oxygen uptake with and without EPI infusion (adapted from
Febbraio et al.[71] with permission). Values are means standard error [(a) n = 20; (b-d) n = 6]. * indicates difference (p < 0.05) when
comparing values at the common time point; # indicates main treatment effect (p < 0.05). CON = without epinephrine infusion; dw
= dry weight.

fused during exercise.[71,72] These observations raise these circumstances pyruvate formation is increased
an important question as to the mechanisms which and subsequently metabolised both aerobically and
may activate carbohydrate oxidation. Although un- anaerobically.
clear, the increase in carbohydrate oxidation may Exacerbated heat stress does not alter plasma
be related to activation of the pyruvate dehydroge- FFA levels[6,13,19,20] but reduces contracting leg FFA
nase complex (PDHC). The activity of PDHC is uptake [13] during exercise. This may suggest that
dependent upon the balance between the activation FFA release by adipocytes is reduced during exer-
of PDH phosphatase and inhibition of PDH kinase. cise and heat stress. This is an interesting potential
PDH phosphatase is activated by increased Ca2+ scenario, given the marked augmented sympatho-
levels while PDH kinase is inhibited by increased adrenal response, as adrenaline is a powerful lipo-
pyruvate and ADP levels.[73] Although pyruvate has lytic agent.[74] This may be the consequence of a
not been measured during exercise and heat stress reduced blood flow to adipocytes. Such a conse-
or with epinephrine infusion, it is possible that in quence would limit albumin availability and pro-

Adis International Limited. All rights reserved. Sports Med 2001; 31 (1)
Energy Metabolism in Exercise and Heat Stress
mote fatty acid re-esterification with adipocytes.
However, Yaspelkis et al.[20] observed similar plasma
glycerol levels during exercise and heat stress. Given
the hydrophilic nature of this metabolite which can
move freely in body fluid compartments, it is un-
likely that fatty acid re-esterification accounts for
the similar FFA levels in plasma and more likely
that during exercise in the heat lipolysis is reduced.
It is possible that heat stress down-regulates hor-
mone sensitive lipase, but this has not been exper-
imentally investigated.
The increase in HGP observed during exercise
and heat stress[9,25] may also be mediated by an aug-
mented sympatho-adrenal response. Apart from ex-
ercise and heat stress, factors such as hypoxia[75]
and increased active muscle mass[76] also demonstr-
ate a parallel increase in HGP and plasma adrena-
line levels. Studies in exercising rats have previously
demonstrated a role for adrenaline in the regulation
of hepatic glucose metabolism.[66,77] Few studies,
however, have examined the role of adrenaline on
HGP in humans. Kjr et al.[78] observed that epi-
nephrine infused at physiological concentrations
into individuals who underwent local anaesthesia
of the sympathetic coeliac ganglion (which inner-
vates the liver, pancreas and adrenal medulla), had
little effect on HGP. In addition, the rise in HGP
during exercise in liver transplant patients (who
lack sympathetic nerve activity to the liver), was
not different when compared with a group of kid-
ney transplant patients who received similar im-
munosuppressive medication as the liver transplant
group.[79] In contrast, Howlett and colleagues[80,81]
have recently demonstrated that epinephrine infused
at physiological concentrations into either endur-
ance trained[80] or bilaterally adrenalectomised[81]
humans increases both circulating glucose levels
and HGP. Hence, it is possible that the relative hy-
perglycaemia and augmented HGP associated with
exercise and heat stress is mediated by an increase
in circulating adrenaline levels.
3. Conclusion
Apart from the major cardiovascular and ther-
moregulatory responses which take place during
Adis International Limited. All rights reserved.
57
acute exercise and heat stress, there are a number
of metabolic alterations which may impact on ex-
ercise performance. Both intramuscular glycogen
use and glycolysis are augmented, while lipid utilisa-
tion appears to decrease during exercise and heat
stress. In addition, high energy phosphagen meta-
bolism and protein catabolism may, in some cir-
cumstances, be increased during exercise in the heat.
Apart from changes which take place within the
contracting skeletal muscle, HGP is also increased
during exercise and heat stress, although this change
is not accompanied by any increase in peripheral
glucose uptake. As a consequence, circulating glu-
cose levels are higher during exercise and thermal
stress. These changes appear to be mediated by mus-
cle temperature per se and by an augmented sym-
patho-adrenal response. In contrast, there is no ev-
idence to suggest that moderate intensity exercise
and heat stress result in alterations to either fibre
type recruitment patterns or contracting muscle ox-
ygen uptake. The key enzymatic regulators or sig-
nals to initiate changes in substrate metabolism dur-
ing exercise and heat stress remain to be elucidated.
References
1. Buskirk ER. Temperature regulation with exercise. Exerc Sport
Sci Rev 1997; 5: 45-88
2. Gisolfi CV, Wenger CB. Temperature regulation during exer-
cise: old concepts, new ideas. Exerc Sport Sci Rev 1984; 12:
339-72
3. Nadel ER. Recent advances in temperature regulation during
exercise in humans. Fed Proc 1985; 44 (7): 2286-92
4. Rowell LB. Human cardiovascular adjustments to exercise and
thermal stress. Physiol Rev 1974; 54: 75-159
5. Sawka MN, Coyle EF. Influence of body water and blood vol-
ume on thermoregulation and exercise performance in the
heat. Med Sci Sports Exerc 1999; 27: 167-218
6. Fink WJ, Costill DL, Van Handel PJ. Leg muscle metabolism
during exercise in the heat and cold. Eur J Appl Physiol 1975;
34: 183-90
7. Febbraio MA, Snow RJ, Hargreaves M, et al. Muscle metabo-
lism during exercise and heat stress in trained men: effect of
acclimation. J Appl Physiol 1994; 76: 589-97
8. Febbraio MA, Snow RJ, Stathis CG, et al. Effect of heat stress
on muscle energy metabolism during exercise. J Appl Physiol
1994; 77: 2827-31
9. Hargreaves M, Angus D, Howlett K, et al. Effect of heat stress
on glucose kinetics during exercise. J Appl Physiol 1996; 81:
1594-97
10. King DS, Costill DL, Fink WJ, et al. Muscle metabolism during
exercise in the heat in unacclimatized and acclimatized hu-
mans. J Appl Physiol 1985; 59 (5): 1350-4
11. Kirwan JP, Costill DL, Kuipers H, et al. Substrate utilization in
leg muscle of men after heat acclimation. J Appl Physiol 1987;
63: 31-5
Sports Med 2001; 31 (1)
58
12. Young A.J, Sawka MN, Levine L, et al. Skeletal muscle meta-
bolism during exercise is influenced by heat acclimation. J
Appl Physiol 1985; 59: 1929-35
13. Gonzalez-Alonso J, Calbet JAL, Nielsen B. Metabolic and ther-
modynamic responses to dehydration-induced reductions in
blood flow in exercising humans. J Physiol 1999; 520: 577-89
14. Hargreaves M, Dillo P, Angus D, et al. Effect of fluid ingestion
on muscle metabolism during prolonged exercise. J Appl
Physiol 1996; 80: 363-6
15. Febbraio MA, Snow RJ, Stathis CG, et al. Blunting the rise in
body temperature reduces muscle glycogenolysis during ex-
ercise in humans. Exp Physiol 1996; 81: 685-93
16. Parkin JM, Carey MF, Zhao S, et al. Effect of ambient temper-
ature on human skeletal muscle metabolism during fatiguing
submaximal exercise. J Appl Physiol 1999; 86: 902-8
17. Kozlowski S, Brzezinska Z, Kruk B, et al. Exercise hyperther-
mia as a factor limiting physical performance: temperature
effect on muscle metabolism. J Appl Physiol 1985: 59: 766-73
18. Maxwell NS, Gardner F, Nimmo MA. Intermittent running:
muscle metabolism in the heat and effect of hypohydration.
Med Sci Sports Exerc 1999: 31: 675-83
19. Nielsen B, Savard G, Richter EA, et al. Muscle blood flow and
muscle metabolism during exercise and heat stress. J Appl
Physiol 1990: 69: 1040-6
20. Yaspelkis III BB, Scroop GC, Wilmore KM, et al. Carbohydrate
metabolism during exercise in hot and thermoneutral environ-
ments. Int J Sports Med 1993; 14: 13-9
21. Young AJ, Sawka MN, Levine L, et al. Metabolic and thermal
adaptations from endurance training in hot and cold water. J
Appl Physiol 1995; 78: 793-801
22. Chesley A, Hultman E, Spriet LL. Effects of epinephrine infu-
sion on muscle glycogenolysis during intense aerobic exer-
cise. Am J Physiol 1995; 268 (1 Pt 1): E127-34
23. Hargreaves M, McConell G, Proietto J. Influence of muscle
glycogen on glycogenolysis and glucose uptake during exer-
cise in humans. J Appl Physiol 1995; 78: 288-92
24. Hespel, P, Richter EA. Mechanisms linking glycogen and
glycogenolytic rate in perfused contracting rat skeletal mus-
cle. Biochem J 1992; 284: 777-80
25. Rowell LB, Brengelmann GL, Blackmon JR, et al. Splanchnic
blood flow and metabolism in heat stressed man. J Appl Phys-
iol 1968; 24: 475-84
26. Dolny DG, Lemon PWR. Effect of ambient temperature on pro-
tein breakdown during prolonged exercise. J Appl Physiol
1988; 64: 550-5
27. Wendling PS, Peters SJ, Heigenhauser GJF, et al. Variability of
triacylglecerol content in human skeletal muscle biopsy sam-
ples. J Appl Physiol 1996; 81: 1150-5
28. Snow RJ, Febbraio MA, Carey MF, et al. Heat stress increases
ammonia accumulation during exercise. Exp Physiol 1993;
78: 847-50
29. Graham TE, Rush JWE, MacLean DA. Skeletal muscle amino
acid metabolism and ammonia production during exercise. In:
Hargreaves M, editor. Exercise metabolism. Champaign (IL):
Human Kinetics, 1995: 131-76
30. Febbraio MA, Murton P, Selig SE, Clark SA, Lambert DL, An-
gus DJ, Carey MF. Effect of CHO ingestion on exercise me-
tabolism and performance in different ambient temperatures.
Medicine and Science in Sports and Exercise 1996 28: 1380-7
31. Kjr M. Hepatic fuel metabolism during exercise. In: Har-
greaves M, editor. Exercise metabolism. Champaign (IL): Hu-
man Kinetics, 1995: 73-97
32. Jeukendrup AE, Wagenmakers AJM, Stegen JH, et al. Carbohy-
drate ingestion can completely suppress endogenous glucose
production during exercise. Am J Physiol 1999; 276 (4 Pt 1):
E672-83
Adis International Limited. All rights reserved.
Febbraio
33. McConell G, Fabris S, Proietto J, et al. Effects of carbohydrate
ingestion on glucose kinetics during exercise. J Appl Physiol
1994; 77: 1537-41
34. Howlett K, Angus DJ, Proietto J, et al. Effect of increased blood
glucose availability on glucose kinetics during exercise. J
Appl Physiol 1998; 84: 1413-7
35. Angus DJ, Febbraio MA, Lasini D, et al. Effect of carbohydrate
ingestion on glucose kinetics during exercise in the heat. J
Appl Physiol. In press
36. Sawka MN, Young AJ, Caderette BS, et al. Influence of heat
stress and acclimation on maximal aerobic power. Eur J Appl
Physiol 1984; 53: 294-8
37. Rowell LB, Blackmon JR, Martin RH, et al. Hepatic clearance
of indocyanine green in man under thermal and exercise
stresses. J Appl Physiol 1965; 20: 384-94
38. Radigan LR, Robinson S. Effect of environmental heat stress
and exercise on renal blood flow and filtration rate. J Appl
Physiol 1949; 2: 185-91
39. Rowell LB. Human circulation: regulation during physical stress.
New York: Oxford University Press, 1986
40. Rowell LB, OLeary DS, Kellogg DL Jr. Integration of cardio-
vascular control systems in dynamic exercise. In: Rowell LB,
Shepherd JT, editors. Handbook of physiology. Section 12.
Exercise: regulation and integration of multiple systems. New
York: Oxford University Press, 1996
41. Young AJ. Energy substrate utilization during exercise in ex-
treme environments. Exerc Sports Sci Rev 1990; 18: 65-117
42. Bell A, Hales J, King R, et al. Influence of heat stress on exer-
cise-induced changes in regional blood flow in sheep. J Appl
Physiol 1983; 55: 1916-23
43. Nielsen B, Hales JRS, Strange S, et al. Human circulatory and
thermoregulatory adaptations with heat acclimation and exer-
cise in a hot, dry environment. J Physiol 1993; 460: 467-85
44. Nielsen B, Strange S, Christensen NJ, et al. Acute and adaptive
responses in humans to exercise in a warm, humid environ-
ment. Pflgers Arch 1997; 434 (1): 49-56
45. Savard GK, Nielsen B, Laszczynska J, et al. Muscle blood flow
is not reduced in humans during moderate exercise and heat
stress. J Appl Physiol 1988; 64: 649-57
46. Smolander J, Louhevaara V. Effects of heat stress on muscle
blood flow during dynamic handgrip exercise. Eur J Appl
Physiol 1992; 65: 215-20
47. Gonzalez-Alonso J, Calbet JAL, Nielsen B. Muscle blood flow
is reduced with dehydration during prolonged exercise in hu-
mans. J Physiol 1999; 513: 895-905
48. Gonzalez-Alonso J, Mora-Rodriguez R, Below PR, et al. Dehy-
dration markedly impairs cardiovascular function in hyper-
thermic endurance athletes during exercise. J Appl Physiol
1997; 82: 1229-36
49. Schumacker PT, Rowland J, Saltz S, et al. Effects of hyperther-
mia and hypothermia on oxygen extraction by tissues during
hypovolemia. J Appl Physiol 1987; 63: 1246-52
50. Clarke MG, Colqhoun EQ, Rattigan S, et al. Vascular and en-
docrine control of muscle metabolism. Am J Physiol 1995;
268: E797-812
51. Gollnick PD, Armstrong RB, Saubert CW 4th, et al. Glycogen
depletion patterns in human skeletal muscle fibres during pro-
longed work. Pflgers Arch 1973; 344 (1): 1-12
52. Saltin B, Hermansen L. Esophageal, rectal and muscle temper-
ature during exercise. J Appl Physiol 1966; 21: 1757-62
53. Florkin M, Stoltz EH. Comprehensive biochemistry. 12. New
York: Elselvier, 1968
54. Edwards RHT, Harris RC, Hultman E, et al. Effect of tempera-
ture on muscle energy metabolism and endurance during suc-
cessive isometric contractions, sustained to fatigue, of the
quadriceps muscle in man. J Physiol 1972; 220: 335-52
Sports Med 2001; 31 (1)
Energy Metabolism in Exercise and Heat Stress
55. Galbo H, Houston ME, Christensen NJ, et al. The effect of water
temperature on the hormonal response to prolonged swim-
ming. Acta Physiol Scand 1979; 105 (3): 326-37
56. Powers SK, Howley ET, Cox R. Blood lactate concentrations
during submaximal work under differing environmental con-
ditions. J Sports Med Phys Fitness 1985; 25 (3): 84-9
57. Greenhaff PL, Ren J-M, Sderlund K, et al. Energy metabolism
in single human muscle fibers during contractions with and
without epinephrine infusion. Am J Physiol 1991; 260 (2 Pt
1): E713-8
58. Jansson E, Hjemdahl P, Kaijser L. Epinephrine induced changes
in muscle carbohydrate metabolism during exercise in male
subjects. J Appl Physiol 1986; 60: 1466-70
59. Spriet LL, Ren J-M, Hultman E. Epinephrine infusion enhances
muscle glycogenolysis during prolonged electrical stimula-
tion. J Appl Physiol 1988; 64: 1439-44
60. Febbraio MA, Carey MF, Snow RJ, et al. Influence of elevated
muscle temperature on metabolism during intense, dynamic
exercise. Am J Physiol 1996; 271: R1251-5
61. Starkie RL, Hargreaves M, Lambert DL, et al. Effect of tem-
perature on muscle metabolism during submaximal exercise.
Exp Physiol 1999; 84: 775-84
62. Uyeda K. Phosphofructokinase. Adv Enzymol Relat Areas Mol
Biol 1979; 48: 193-244
63. Ren J-M, Hultman E. Regulation of phosphorylase a activity in
human skeletal muscle. J Appl Physiol 1990; 67: 919-23
64. Galbo H. Hormonal and metabolic adaptations to exercise. New
York: Thiemme-Stratton Inc., 1983
65. Richter EA, Ruderman NB, Gavras H, et al. Muscle glycoge-
nolysis during exercise: dual control by epinephrine and con-
tractions. Am J Physiol 1982; 242 (1): E25-32
66. Richter EA, Sonne B, Christensen NJ, et al. Role of epinephrine
for muscular glycogenolysis and pancreatic hormone secre-
tion in running rats. Am J Physiol 1981; 240 (5): E526-32
67. Issekutz, B. Effect of epinephrine on carbohydrate metabolism
in exercising dogs. Metabolism 1985; 34: 457-64
68. Hashimoto I, Knudson MB, Noble EG, et al. Exercise-induced
glycogenolysis in sympathectomized rats. Jpn J Physiol 1982;
32: 153-60
69. Issekutz B. Effect of -adrenergic blockade on lactate turnover
in exercising dogs. J Appl Physiol 1984; 57: 1754-59
70. Wendling PS, Peters SJ, Heigenhauser GJF, et al. Epinephrine
infusion does not enhance net muscle glycogenolysis during
Adis International Limited. All rights reserved.
59
prolonged aerobic exercise. Can J Appl Physiol 1996; 21:
271-84
71. Febbraio MA, Lambert DL, Starkie RL, et al. Effect of epineph-
rine on muscle glycogenolysis during exercise in trained men.
J Appl Physiol 1998; 84: 465-70
72. Turner MJ, Howley ET, Tanaka H, et al. Effect of graded epi-
nephrine infusion on blood lactate response to exercise. J
Appl Physiol 1995; 79: 1206-11
73. Putman CT, Spriet LL, Hultman E, et al. Pyruvate dehydroge-
nase activity and acetyl group accumulation during exercise
after different diets. Am J Physiol 1993; 265 (5 Pt 1): E752-60
74. Martin WH III. Effects of acute and chronic exercise on fat
metabolism. Exerc Sports Sci Rev 1996; 24: 203-31
75. Cooper DM, Wasserman DW, Vranic M, et al. Glucose turnover
in response to exercise during high- and low FIO2 breathing
in man. Am J Physiol 1986; 251: E209-14
76. Kjr M, Kiens B, Hargreaves M, et al. Influence of active mus-
cle mass on glucose homeostasis during exercise in humans.
J Appl Physiol 1991; 71: 552-7
77. Sonne B, Mikines KJ, Richter EA, et al. Role of liver nerves
and adrenal medulla in glucose turnover in running rats. J
Appl Physiol 1985; 59: 1640-6
78. Kjr M, Engfred K, Fernandes A, et al. Regulation of hepatic
glucose production during exercise in humans: role of sym-
pathoadrenergic activity. Am J Physiol 1993; 265 (2 Pt 1):
E275-83
79. Kjr M, Keiding S, Engfred K, et al. Glucose homeostasis dur-
ing exercise in humans with a liver or kidney transplant. Am
J Physiol 1995; 268 (4 Pt 1): E636-44
80. Howlett K, Febbraio MA, Hargreaves M. Liver glucose produc-
tion during strenuous exercise in humans: role of epinephrine.
Am J Physiol 1999; 276 (6 Pt 1): E1130-5
81. Howlett K, Galbo H, Lorentsen J, et al. Effect of adrenaline on
glucose kinetics during exercise in adrenalectomised humans.
J Physiol 1999; 519: 911-21
Correspondence and offprints: Mark A. Febbraio, Exercise
Physiology & Metabolism Laboratory, Department of Phys-
iology, University of Melbourne, Parkville, VIC 3052, Aus-
tralia.
E-mail: m.febbraio@physiology.unimelb.edu.au
Sports Med 2001; 31 (1)