Fat Metabolism during Exercise

by taratuta

Category: Documents





Fat Metabolism during Exercise
Chapter 13
Fat Metabolism during Exercise
In the search for strategies to improve athletic
performance, recent interest has focused on
several nutritional procedures which may,
theoretically, promote fatty acid (FA) oxidation,
attenuate the rate of muscle glycogen utilization
and improve exercise capacity (for reviews, see
Chapter 14 and Lambert et al. 1997; Hawley et al.
1998). The aim of this chapter is to provide the
reader with a general overview of the role of
endogenous fat as an energy source for muscular
contraction, to discuss the effects of exercise
intensity and duration on the regulation of fat
metabolism, and to give a synopsis of some of the
factors which may potentially limit FA mobilization, uptake and oxidation by human skeletal
muscle during exercise.
Fat as an energy source for
physical activity
The human body utilizes carbohydrate (CHO),
fat and, to a lesser, extent protein as fuel for muscular work. Fat as an energy source has several
advantages over CHO: the energy density of
fat is higher (37.5 kJ · g–1 (9 kcal · g–1) for stearic
acid vs. 16.9 kJ · g–1 (4 kcal · g–1) for glucose), therefore the relative weight as stored energy is lower.
FAs provide more adenosine triphosphate (ATP)
per molecule than glucose (147 vs. 38 ATP).
However, in order to produce the equivalent
amount of ATP, the complete oxidation of FA
requires more oxygen than the oxidation of CHO
(6 vs. 26 molecules of oxygen per molecule of
substrate for the complete oxidation of glucose
and stearic acid, respectively). Using CHO as a
fuel, 21 kJ (5 kcal) of energy are available for
each litre of oxygen used, whereas only 19.7 kJ
(4.7 kcal) per litre of oxgyen are available when
fat is the sole fuel oxidized: this may be important when the oxygen supply is limited.
On the other hand, for every gram of CHO
stored as glycogen, approximately 2 g of water
are stored (Holloszy 1990). Consequently, the
amount of glycogen stored in muscle and liver is
limited to about 450 g in an average-sized adult.
Of interest is that although skeletal muscle comprises up to 40% of body mass in well-trained
individuals, CHO utilization by muscle in the
resting or postabsorptive state is minimal,
accounting for less than 10% of total glucose
turnover (Felig & Wahren 1975).
Fat can be stored in much greater amounts. In a
healthy, untrained male, up to 20 kg of fat can be
stored, mainly in adipose tissue: in the obese
individual, the fat store may exceed 100 kg. Even
in highly trained athletes with much lower levels
of adipose tissue, endogenous fat stores still far
exceed the requirements of all athletic pursuits.
Both FA stored in adipose tissue and fat entering the circulation after a meal can serve as
potential energy sources for the muscle cell (Fig.
13.1). For humans ingesting a typical Western
diet (approximately 35% of energy from fat), FAs
are comprised of approximately 40% oleate, 25%
palmitate, 15% stearate and 10% linoleate. The
remainder is thought to be a mixture of both
fat metabolism during exercise
Adipose tissue
Fig. 13.1 The storage and
mobilization of peripheral
adipose and intramuscular
triacylglycerol (TG). TG from
peripheral adipose tissue can be
broken down to glycerol and free
fatty acids (FFAs). FFAs can be
mobilized by binding to plasma
albumin for transport into the
systemic circulation to skeletal
muscle. Intramuscular TG can
also be broken down to glycerol
plus fatty acids, which can enter
the mitochondria for oxidation
during exercise. TCA,
tricarboxylic acid. From Coyle
(1997), with permission.
Blood plasma
(210 000 kJ)
Intramuscular TG
(12 600 kJ)
(c. 8400 kJ)
saturated and unsaturated FAs with chain
lengths of 12–20 carbon atoms (Havel et al.
Small but physiologically important amounts
of FA are also stored as triacylglycerols (TG)
inside the muscle cells: the total muscle mass
may contain up to 300 g of fat of which the major
part is stored within the myocyte as small lipid
droplets (Björkman 1986). FAs liberated from TG
stored in adipocytes are released to blood, where
they are bound to albumin. The albumin concentration of blood is about 6 mm, while the concentration of FA is about 0.2–1.0 mm. As albumin can
bind up to eight FAs, the albumin transport
capacity is far in excess of the amount of FAs
bound under physiological circumstances and
therefore cannot be the limiting factor for FA oxidation by muscle.
FA can also be derived from the triacylglycerol
core of circulating chylomicrons and very low
density lipoproteins (VLDL), which are both
formed from dietary fat in the postabsorptive state. Chylomicrons are formed in the
epithelial wall of the intestine and reach the
blood stream after passage through the lymphatic system. VLDLs are synthesized in the
liver after which they are released directly into
the blood stream.
FFA Albumin
Fatty acids
TCA cycle and
electron transport
(420 kJ)
Effects of exercise intensity and
duration of fat metabolism
More than 50 years ago, Christensen and Hansen
(1939) provided evidence from respiratory gas
exchange measurements that fat was a major
fuel for exercise metabolism. Since that time, a
number of investigations have provided evidence that plasma FAs contribute a significant
portion to the energy demands of mild-tomoderate exercise. However, until recently the
rates of whole-body lipolysis had only been measured during very low-intensity exercise, and in
untrained or moderately active individuals.
Our understanding of the regulation of
endogenous fat and CHO metabolism in relation
to exercise intensity and duration has been
advanced considerably by modern-day studies
which have used a combination of stable isotope
techniques in association with conventional indirect calorimetry (Romijn et al. 1993, 1995; Sidossis
& Wolfe 1996; Siddossis et al. 1996, 1997). As the
three most abundant FAs are oxidized in proportion to their relative presence in the total plasma
FA pool (Havel et al. 1964), total plasma FA kinetics can be reliably estimated from stable isotope
studies using infusions of either palmitate or
oleate (when the concentrations of total FAs and
nutrition and exercise
palmitate and oleate are known). Palmitate is a
saturated 16-C FA (CH3(CH2)14COOH) whose
kinetics closely resemble those of most other
long-chain FAs (Havel et al. 1964). As such, the
rate of appearance (Ra) of palmitate gives an
index of the release of FAs into the plasma. The
Ra of glycerol, on the other hand, gives an index
of whole-body lipolysis. Rates of total fat and
CHO oxidation are determined by indirect
calorimetry. The use of these methods has
allowed estimates to be made of the rates of lipid
kinetics, including the contribution to energy
expenditure from peripheral lipolysis occurring
in the adipocytes and from intramuscular
During low-intensity exercise (25% of maxi.
mum oxygen uptake (Vo2max.)), peripheral lipolysis is strongly stimulated, with little lipolysis of
intramuscular TG (Fig. 13.2). Similarly, CHO oxidation appears to be met exclusively by blood
glucose with little or no muscle glycogen utilization. Ra of FA into the plasma and their oxidation
are highest during exercise at 25% of Vo2max., and
decline progressively as the exercise intensity
Energy expenditure (J.kg–1.min–1)
Muscle glycogen
Muscle triglyceride
Plasma FFA
Intensity (% VO2max)
Fig. 13.2 The maximal contribution to energy
expenditure from endogenous fat and carbohydrate,
expressed as a function
. of increasing exercise intensity.
FFA, free fatty acids; Vo2max., maximal oxygen uptake.
From Romijn et al. (1993), with permission from the
American Physiological Society.
increases. Conversely, although intramuscular
TG (and glycogen) do not contribute significantly to energy production during low-intensity
work, fat oxidation is highest during exercise at
about 65% of Vo2max. (Fig. 13.2). At this intensity,
lipolysis in both peripheral adipocytes and intramuscular TG stores attains its highest rates, and
these two sources contribute about equally to the
rate of total fat oxidation. With an increase
in exercise intensity to 85% of Vo2max., total fat
oxidation falls. This is mainly due to a suppression in the Ra of FA into the plasma, presumably
caused by the increases in circulating plasma
catecholamines, which stimulate muscle
glycogenolysis and glucose uptake. Lipolysis of
intramuscular TG does not increase substantially
with an increase in exercise intensity from 65%
to 85% of Vo2max., indicating that lipolysis of
peripheral adipose tissue and lipolysis of intramuscular TG are regulated differently. Further
evidence for this hypothesis comes from studies
which have increased FA delivery (by intravenous infusion of lipid and heparin) during
intense (85% of Vo2max.) exercise in well-trained
subjects (Romijn et al. 1995). These data reveal
that even when plasma FA concentration is artificially maintained above 1 mm, this only partly
restores fat oxidation to those (higher) levels seen
at more moderate intensity (65% of Vo2max.) exercise. Taken collectively, these observations indicate that factors other than FA availability play
an important role in the regulation of FA oxidation during high-intensity exercise (see following
With regard to the effects of exercise duration
on fat metabolism, there is little change in either
the rates of total fat or total CHO oxidation after
2 h compared with the first 30 min of exercise at
25% of Vo2max.. However, at an intensity of 65% of
Vo2max., there is a progressive increase in the Ra
of FA into the plasma (and presumably their oxidation) and glucose availability over time. After
2 h of cycling at this intensity, there is no change
in either the rates of total fat and total CHO oxidation compared with the situation after 30 min
of exercise. Thus, it is likely that the contribution
of intramuscular substrates (TG and glycogen)
fat metabolism during exercise
to total energy expenditure decreases with increasing exercise duration during prolonged
(> 90 min) moderate-intensity (65% of Vo2max.)
Factors limiting fat oxidation
by muscle
Factors limiting fatty acid uptake
by muscle cells
As previously discussed, the metabolism of FA
derived from adipose tissue lipolysis constitutes
a major substrate for oxidative metabolism, especially during prolonged, low-intensity exercise.
The metabolism of long-chain FA is a complex
and integrated process that involves a number of
events: FA mobilization from peripheral adipose
tissue, transport in the plasma, transport and
permeation across muscle cell membranes and
interstitium, cytoplasmic transport, and intracellular metabolism. The first stage in this process,
the mobilization of lipids, plays a key role in the
subsequent regulation of FA utilization during
both the resting state and exercise.
During perfusion of the muscle capillaries, FA
bound to albumin or stored in the core of chylomicrons and VLDL have to be released prior to
transport across the vascular membrane. In the
case of VLDL and chylomicrons, this is achieved
by the action of the enzyme lipoprotein lipase
(LPL). LPL is synthesized within the muscle
cell and, after an activation process, is translocated to the vascular endothelial cell membrane
where it exerts its enzymatic action on TG.
LPL also expresses phospholipase A2 activity
which is necessary for the breakdown of the
phospholipid surface layer of the chylomicrons
and lipoproteins.
LPL activity is upregulated by caffeine, catecholamines and adrenocorticotrophic hormone
(ACTH), and downregulated by insulin (for
review, see Jeukendrup 1997). After TG hydrolysis, most of the FA will be taken up by muscle,
whereas glycerol will be taken away via the
bloodstream to the liver, where it may serve as
a gluconeogenic precursor. During the postab-
sorptive state, the concentration of circulating
TG in plasma is usually higher than that of FA, in
contrast to the fasting state when chylomicrons
are practically absent from the circulation.
Nevertheless, the quantitative contribution of
circulating TG to FA oxidation by the exercising
muscle cells in humans is somewhat uncertain.
Due to technical limitations, no reliable data are
available to determine whether FA derived from
the TG core of VLDL or chylomicrons substantially contribute to overall FA utilization.
However, it is interesting to note that even a
small extraction ratio of the order of 2–3% of
FA/TG could potentially cover over up to 50%
of total exogenous FA uptake and subsequent
oxidation (Havel et al. 1967).
The arterial concentration of FA strongly
affects FA uptake into muscle both at rest and
during low-intensity exercise (for review, see
Bulow 1988). This implies an FA gradient from
blood to muscle in these conditions, which is
achieved by a relatively rapid conversion of FA,
taken up by the muscle cell, to fatty acyl-CoA.
The rate of the latter reaction step is controlled by
fatty acyl-CoA synthetase. During transport of
FA from blood to muscle, several barriers may
limit FA uptake, including the membranes of the
vascular endothelial cell, the interstitial space
between endothelium and muscle cell, and
finally the muscle cell membrane (for review, see
van der Vusse & Reneman 1996).
Uptake by endothelial cells is most likely
protein mediated. Both albumin-binding protein
and membrane-associated FA-binding proteins
(FABP) may play a role. After uptake, most FAs
will diffuse from the luminal to the abluminal
membrane of the endothelial cells as free molecules. Although small amounts of FABP are
present at this site, their role in transmembrane
FA transport is assumed to be unimportant. Once
in the interstitial space, albumin will bind the
FAs for transport to the muscle cell membrane.
Here the FAs are taken over by a fatty-acidtransporting protein, or will cross the membrane
directly because of their lipophilic nature. In the
sarcoplasm, FABP, which is present in relatively
high concentrations, is crucial for FA transport to
nutrition and exercise
the mitochondria. This transport is assumed not
to ultimately limit FA oxidation.
As indicated earlier, an alternative source of
FA are TGs present inside the skeletal muscle
cells. For the storage of FA, glycerol is obtained
from glycolysis (as glycerol-3-phosphate) which
reacts with fatty acyl-CoA, after which further
condensation to and storage as TG take place in
small fat droplets, mainly located in the proximity of the mitochondrial system. It has been
suggested that adipocytes, positioned between
muscle cells may also supply FA for oxidation,
although the physiological significance of this
has never been accurately quantified. During
periods of increased muscle contractile activity,
muscle lipase is activated by hormonal actions
which leads to the release of FA from the intramuscular TG. Noradrenaline infusion has been
observed to cause a significant reduction in
muscle TG, and insulin counteracts this effect.
Apart from hormonal stimuli, there is also local
muscular control of lipase activity, shown by the
observation that electrical stimulation of muscle
enhances TG breakdown.
Compared to fast twitch (type II) muscle fibres,
slow twitch (type I) fibres have a high lipase
activity (Gorski 1992) as well as TG content
(Essen 1977). Interestingly, TG storage within the
muscle cell can be increased by regular
endurance training (Morgan et al. 1969; Howald
et al. 1985; Martin 1996). However, whereas some
studies report an increased utilization of intramuscular triacylglycerol after endurance training (Hurley et al. 1986; Martin et al. 1993),
others (Kiens 1993) find no change. These
conflicting results may simply be a reflection of
the different type of exercise modes employed
(cycling vs. dynamic knee-extension exercise),
which result in marked differences in circulating
catecholamine levels. On the other hand, an
inability to detect exercise-induced perturbations in intramuscular TG content does not
exclude the possibility that while FAs are being
hydrolysed from the intramuscular TG pool, TG
is also being synthesized, with the net result that
there is no change in concentration (Turcotte et al.
1995). If indeed the intramuscular TG pool is in a
state of constant turnover, a net decline in stores
would only be observed when the rate of utilization of intramuscular TG is greater than the rate
of TG synthesis.
Factors limiting fatty acid oxidation
by muscle cells
As previously discussed, a relatively high percentage of the total energy production is derived
from FA oxidation at rest and during lowintensity exercise. However, with increasing
exercise intensities, particularly above 70–80% of
Vo2max., there is a progressive shift from fat to
CHO (Gollnick 1985), indicating a limitation to
the rate of FA oxidation. Several explanations for
this shift from fat to CHO have been proposed,
including an increase in circulating catecholamines, which stimulates glycogen breakdown in both the muscle and liver. However, the
increased lactate formation (and accompanying
hydrogen ion accumulation) which occurs when
glycogen breakdown and glycolytic flux are
increased also suppresses lipolysis. The net
result will be a decrease in plasma FA concentration and hence in the supply of FA to muscle
cells. As a consequence, enhanced CHO oxidation will most likely compensate for the reduced
FA oxidation.
Another reason for this substrate shift is the
lower ATP production rate per unit of time from
fat compared with that from CHO, combined
with the fact that more oxygen is needed for the
production of any given amount of ATP from fat
than from CHO, as previously noted. Finally,
limitations in the FA flux from blood to mitochondria might explain the shift from fat to
CHO at higher exercise intensities. This flux is
dependent on the concentration of FA in the
blood, capillary density, transport capacity
across vascular and muscle cell membranes,
mitochondrial density and mitochondrial capacity to take up and oxidize FA. The latter depends
on the action of the carnitine transport system
across the mitochondrial membrane which is
fat metabolism during exercise
regulated by malonyl-CoA (Winder et al. 1989).
During exercise, malonyl-CoA formation is
reduced and therefore the capacity to transport
FAs across the mitochondrial inner membrane is
The rate of oxidation of FA is the result of three
1 Lipolysis of TG in adipose tissue and circulating TG and transport of FA from blood plasma to
the sarcoplasm.
2 Availability and rate of hydrolysis of intramuscular TG.
3 Activation of the FA and transport across the
mitochondrial membrane.
It is likely that the first two processes pose the
ultimate limitations to fat oxidation observed
during conditions of maximal FA flux. This is
most evident during both short-term intense
exercise or during the initial phase of a long-term
exercise. In this condition, lipolysis in adipose
tissue and in muscle TG is insufficiently upregulated to result in enhanced FA supply. The result
will be that the rate of FA oxidation exceeds the
rate at which FAs are mobilized, leading to a fall
in plasma FAs and intracellular FAs in muscle. As
a consequence, the use of CHO from glycogen
must be increased to cover the increased energy
Direct evidence that the rate of FA oxidation
can be limited by a suppression of lipolysis, at
least during low-to-moderate intensity (44% of
Vo2max.) exercise, comes from a recent investigation by Horowitz et al. (1997). They showed that
CHO ingestion (0.8 g · kg–1 body mass) before
exercise, which resulted in a 10–30 mU · ml–1
elevation in plasma insulin concentration, was
enough to reduce fat oxidation during exercise,
primarily by a suppression of lipolysis. They also
showed that fat oxidation could be elevated (by
about 30%) when plasma FA concentration was
increased via Intralipid and heparin infusion,
even when CHO was ingested. However, the
increase in lipolysis was not sufficient to restore
fat oxidation to those levels observed after
fasting. Taken collectively, these results suggest
that CHO ingestion (and the concomitant eleva-
tion in plasma insulin concentration) has another
(additional) effect on reducing the rates of FA
oxidation by exercising skeletal muscle.
In contrast to body CHO reserves, fat stores are
abundant in humans and represent a vast source
of fuel for exercising muscle. FAs stored both in
peripheral adipose tissue and inside the muscle
cells serve as quantitatively important energy
sources for exercise metabolism. During low.
intensity work (25% of Vo2max.), plasma FA liberated from adipose tissue represents the main
source of fuel for contracting muscle, with little
or no contribution from intramuscular lipolysis
to total energy metabolism. On the other hand,
during moderate-intensity exercise (65% of
Vo2max.), fat metabolism is highest, with the contribution of lipolysis from peripheral adipocytes
and of intramuscular TG stores contributing
about equally to total fat oxidation. During high.
intensity exercise (85% of Vo2max.), there is a
marked reduction in the rate of entry of FA into
the plasma, but no further increase in intramuscular TG utilization. At such workrates, muscle
glycogenolysis and the accompanying increased
lactate concentration suppress the rates of
whole-body lipolysis.
The major hormonal changes which promote
lipolysis during exercise are an increase in catecholamine concentration and a decline in insulin
levels, both of which facilitate activation of LPL.
The rate of FA oxidation is also regulated indirectly by the oxidative capacity of the working
muscles and the intramuscular concentration
of malonyl-CoA. The muscle tissue level of
malonyl-CoA is dependent on the prevailing
concentrations of plasma glucose and insulin:
elevated circulating levels of these two compounds is associated with elevated concentrations of malonyl-CoA. Any increase in glycolytic
flux therefore may directly inhibit long-chain FA
oxidation, possibly by inhibiting its transport
into the mitochondria (Sidossis & Wolfe 1996;
Sidossis et al. 1996; Coyle et al. 1997).
nutrition and exercise
Björkman, O. (1986) Fuel utilization during exercise.
In Biochemical Aspects of Physical Exercise (ed. O.
Björkman), pp. 245–260. Elsevier, Amsterdam.
Bulow, J. (1988) Lipid mobilization and utilization. In
Principles of Exercise Biochemistry: Medicine and Sports
Science (ed. J.R. Poortmans), pp. 140–163. Karger,
Christensen, E.H. & Hansen, O. (1939) Respiratorischer
quotient und O2-aufnahme (Respiratory quotient
and O2 uptake). Scandinavian Archives of Physiology
81, 180–189.
Coyle, E.F. (1997) Fuels for sport performance. In Perspectives in Exercise Science and Sports Medicine. Vol.
10. Optimizing Sport Performance (ed. D.R. Lamb & R.
Murray), pp. 95–137. Cooper Publishing, Carmel,
Coyle, E.F., Jeukendrup, A.E., Wagenmakers, A.J.M. &
Saris, W.H.M. (1997) Fatty acid oxidation is directly
regulated by carbohydrate metabolism during exercise. American Journal of Physiology 273, E268–E275.
Essen, B. (1977) Intramuscular substrate utilization
during prolonged exercise. In The Marathon: Physiological, Medical, Epidemiological, and Psychological
Studies (ed. P. Milvy), pp. 30–44. New York Academy
of Sciences, New York.
Felig, P. & Wahren, J. (1975) Fuel homeostasis in exercise. New England Journal of Medicine 293, 1078–1084.
Gollnick, P.D. (1985) Metabolism of substrates: energy
substrate metabolism during exercise and as modified by training. Federation Proceedings 44, 353–357.
Gorski, J. (1992) Muscle triglyceride metabolism
during exercise. Canadian Journal of Physiology and
Pharmacology 70, 123–131.
Havel, R.J., Carlson, L.A., Ekelund, L.G. & Holmgren,
A. (1964) Turnover rate and oxidation of different
fatty acids in man during exercise. Journal of Applied
Physiology 19, 613–619.
Havel, R.J., Pernow, B. & Jones, N.L. (1967) Uptake and
release of free fatty acids and other metabolites in the
legs of exercising men. Journal of Applied Physiology
23, 90–99.
Hawley, J.A., Brouns, F. & Jeukendrup, A.E. (1998)
Strategies to enhance fat utilisation during exercise.
Sports Medicine 25, 241–257.
Holloszy, J.O. (1990) Utilization of fatty acids during
exercise. In Biochemistry of Exercise. Vol. VII (ed. A.W.
Taylor, P.D. Gollnick & H.J. Green et al.), pp. 319–327.
Human Kinetics, Champaign, IL.
Horowitz, J.F., Mora-Rodriguez, R., Byerley, L.O. &
Coyle, E.F. (1997) Lipolytic suppression following
carbohydrate ingestion limits fat oxidation during
exercise. American Journal of Physiology 273, E768–
Howald, H., Hoppeler, H. & Claassen, H. (1985) Influences of endurance training on the ultrastructural
composition of the different muscle fiber types in
humans. Pflugers Archives 403, 369–376.
Hurley, B.F., Nemeth, P.M., Martin, W.H., Hagberg,
J.M., Dalsky, G.P. & Holloszy, J.O. (1986) Muscle
triglyceride utilization during exercise: effect of
training. Journal of Applied Physiology 60, 562–567.
Jeukendrup, A.E. (1997) Fat metabolism during exercise, a review. In Aspects of Carbohydrate and Fat
Metabolism, pp. 21–71. De Vrieseborch: Haarlem.
Kiens, B., Essen-Gustavsson, B., Christensen, N.J. &
Saltin, B. (1993) Skeletal muscle substrate utilisation
during submaximal exercise in man: effect of
endurance training. Journal of Physiology (London)
469, 459–478.
Lambert, E.V., Hawley, J.A., Goedecke, J., Noakes, T.D.
& Dennis, S.C. (1997) Nutritional strategies for
promoting fat utilization and delaying the onset of
fatigue during prolonged exercise. Journal of Sports
Science 15, 315–324.
Martin, W.H. (1996) Effects of acute and chronic exercise on fat metabolism. In Exercise and Sports Science
Reviews, Vol. 24 (ed. J.O. Holloszy), pp. 203–231.
Williams & Wilkins, Baltimore.
Martin, W.H., Dalsky, G.P. & Hurley, B.F. (1993) Effect
of endurance training on plasma free fatty acid
turnover and oxidation during exercise. American
Journal of Physiology 265, E708–E714.
Morgan, T.E., Short, F.A. & Cobb, L.A. (1969) Effect of
long-term exercise on skeletal muscle lipid composition. American Journal of Physiology 216, 82–86.
Romijn, J.A., Coyle, E.F., Sidossis, L.S. et al. (1993) Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.
American Journal of Physiology 265, E380–E391.
Romijn, J.A., Coyle, E.F., Sidossis, L.S., Zhang, X.J. &
Wolfe, R.R. (1995) Relationship between fatty acid
delivery and fatty acid oxidation during strenuous
exercise. Journal of Applied Physiology 79, 1939–
Sidossis, L.S. & Wolfe, R.R. (1996) Glucose and insulininduced inhibition of fatty acid oxidation: the
glucose fatty-acid cycle reversed. American Journal of
Physiology 270, E733–E738.
Sidossis, L.S., Stuart, C.A., Schulman, G.I., Lopaschuk,
G.D. & Wolfe, R.R. (1996) Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid
entry into the mitochondria. Journal of Clinical Investigation 98, 2244–2250.
Sidossis, L.S., Gastaldelli, A., Klien, S. & Wolfe, R.R.
(1997) Regulation of plasma free fatty acid oxidation
during low- and high-intensity exercise. American
Journal of Physiology 272, E1065–E1070.
Turcotte, L.P., Richter, E.A. & Kiens, B. (1995) Lipid
metabolism during exercise. In Exercise Metabolism
fat metabolism during exercise
(ed. M. Hargreaves), pp. 99–130. Human Kinetics,
Champaign, IL.
van der Vusse, G.J. & Reneman, R.S. (1996) Lipid
metabolism in muscle. In Handbook of Physiology.
Section 12. Exercise: Regulation and integration of multiple systems (ed. L.B. Rowell & J.T. Shepherd), pp.
952–994. American Physiological Society, Oxford
Press, New York.
Winder, W.W., Arogyasami, J., Barton, R.J., Elayan, I.M.
& Vehrs, P.R. (1989) Muscle malonyl-CoA decreases
during exercise. Journal of Applied Physiology 67,
Fly UP