J. Endocrinol. Invest.
35: 686-691, 2012
DOI: 10.3275/8466
SHORT REVIEW
Maximal lipid oxidation during exercise: A target for individualizing
endurance training in obesity and diabetes?
J.F. Brun1, D. Malatesta2, and A. Sartorio3,4
1INSERM U1046 “Physiologie et Médecine Exprimentale du Cœur et du Muscle”, Université Montpellier 1, Université Montpellier
2; CHRU Montpellier, Département de Physiologie Clinique; Equipe d’Exploration Métabolique (CERAMM) Hôpital Lapeyronie,
Montpellier, France; 2Institute of Sport Sciences University of Lausanne (ISSUL), Department of Physiology, Faculty of Biology and
Medicine, Lausanne, Switzerland; 3Istituto Auxologico Italiano, IRCCS, Laboratorio Sperimentale Ricerche Auxo-endocrinologiche;
4Divisione Malattie Metaboliche, Milan and Verbania, Italy
ABSTRACT. This review summarizes the rationale for person-
alized exercise training in obesity and diabetes, targeted at
the level of maximal lipid oxidation as can be determined by
exercise calorimetry. This measurement is reproducible and
reflects muscles’ ability to oxidize lipids. Targeted training at
this level is well tolerated, increases the ability to oxidize lipids
INTRODUCTION
Chronic physical inactivity is a well-established etiologi-
cal factor for many largely widespread diseases (1-4), in-
cluding obesity (5) and diabetes (6), whose course has
been reported to be positively influenced by regular mus-
cular activity (7).
Based on this evidence, a recent editorial urges public
policy makers to consider structured exercise and phys-
ical activity programs as worthy of insurance reimburse-
ment to promote health, especially in high-risk popula-
tions (8). Exercise is more efficient if structured, i.e., per-
formed after a precise prescription and with a serious
coaching and follow-up (9).
Guidelines for exercise prescription are regularly released
(7). In metabolic diseases it is mostly considered as a
method to induce an energy deficit (10), and duration of
exercise seems to be the major determinant of its effi-
ciency (11).
Recent studies point out the potential interest of short
duration high-intensity exercise (12) which results in im-
portant improvements of muscle metabolism. However,
the variety of exercise that has accumulated the greatest
body of evidence for its efficiency is endurance exercise
(13), which is easier to apply at low intensity in very
sedentary patients in whom strenuous exercise is poorly
tolerated and even potentially harmful (14).
In order to obtain the best results with low-intensity ex-
ercise, it is interesting to develop strategies to improve its
Key-words: Diabetes, exercise, fat oxidation, indirect calorimetry, obesity, physical
training, sedentariness.
Correspondence: J.-F. Brun, INSERM U1046, Département de Physiologie Clinique,
Equipe d’Exploration Métabolique (CERAMM), Hôpital Lapeyronie, 34295 Montpel-
lier cedex 5 (France).
E-mail: j-brun@chu-montpellier.fr
Accepted May 30, 2012.
First published online June 25, 2012.
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during exercise and improves body composition, lipid and in-
flammatory status, and glycated hemoglobin, thus repre-
senting a possible future strategy for exercise prescription in
patients suffering from obesity and diabetes.
(J. Endocrinol. Invest. 35: 686-691, 2012)
©2012, Editrice Kurtis
efficiency. Such a strategy will be the topic of this review,
which will focus on a concept of exercise prescription that
generates a growing number of studies, the concept of
maximal lipid oxidation during muscular activity.
THE CONCEPT OF “INDIVIDUALIZED TRAINING”
AND A PROPOSAL TO APPLY IT IN OBESITY
AND DIABETES
For training patients suffering from respiratory and heart
diseases, the “individualization concept”, has been pro-
posed. After an exercise-test, a specific level for each sub-
ject is defined (in this case the ventilatory threshold). This
approach has been reported to provide better results (15).
Recommendations for exercise in diabetes (6) and obesi-
ty (16) refer only to a type of activity (endurance, resis-
tance) and to an amount of energy deficit, with no refer-
ence to such an “individualization concept”.
Clearly, this energy deficit is a major determinant of the ef-
ficiency of exercise (10), but individual responsiveness to
exercise-induced fat loss seems to be improved by other
factors. Among them there is the ability to oxidize lipids
at rest (17), and there is limited but growing evidence to
suggest that the ability to oxidize lipids during exercise is
also a determinant of exercise-induced weight loss (18), as
was postulated 10 years ago (19). Conversely, a greater re-
liance on carbohydrates (CHO), resulting in a negative
carbohydrate balance, predicts greater fat gain (20).
These findings, although they need to be further investi-
gated, provide a rationale for promoting a protocol of ex-
ercise aiming at improving lipid oxidation, as an attempt to
increase their efficiency. Targeting exercise training at the
level where lipid oxidation is maximal may represent such
a strategy. In addition, although this issue is beyond the
scope of this review, it is clear that lipid accumulation in
adipose tissue, liver, and muscle represents a major ab-
normality in obesity and diabetes (21), and this is one more
reason to target exercise on lipid oxidation.
 Lipid oxidation during exercise

LIPID METABOLISM DURING EXERCISE
The most important substrate oxidized during exercise is
glucose (22), but exercise may significantly increase the use
of lipids by several ways that are summarized in Figure 1
(35, 36).
During steady-state exercise performed at low intensity,
there is an intensity of exercise that elicits the maximum
oxidation of lipids which has been termed LIPOXmax
(point of maximal lipid oxidation) (23), FATOXmax (max-
imal lipid oxidation at exercise) (24) or FATmax (maximal
lipid oxidation at exercise) (25), as explained below.
Increased lipid oxidation may also result from exercise-
induced glycogen depletion, either when exercise du-
ration exceeds 1 h, or when exercise has been per-
formed at high intensity (and thus oxidizing almost ex-
clusively CHO). In this case several papers have de-
scribed a compensatory rise in lipid oxidation (26), which
in some cases has been found to be of a similar magni-
tude compared to that which occurs during low-intensi-
ty exercise. However, in other studies post-exercise lipid
oxidation has been shown to be almost insignificant (27,
28). Accordingly, Warren (29) states that to be sure that
an exercise bout results in lipid oxidation, the safest so-
lution is to exercise in the LIPOXzone (range of power
intensities where lipid oxidation is maximal ±5%) (i.e., at
low- to medium-intensity). A study by Meyer (30) shows
that at such low-intensities lipid oxidation remains quite
stable at steady state over 1 h.
PHYSIOLOGICAL EXPLANATION OF THE U-SHAPED
CURVE OF LIPID OXIDATION DURING EXERCISE
Below 25% of VO2max, fat has been reported to be the ma-
jor energy supply for the muscle, which virtually uses no
glycogen as a source of energy (22, 31). Above this level,
glycogen oxidation gradually increases (32, 33), and fat
oxidation increases until the LIPOXmax/FAT(ox)max and
then decreases (33).
The reasons for this decrease have been reviewed else-
where (34). Extracellular lipid supply is not limiting, since
lipid oxidation decreases even if additional fat is provid-
ed to the cell. Limiting steps seem to be the entrance in-
to mitochondria, governed by carnitine palmitoyl trans-
ferase 1 (CPT-I), which can be inhibited by Malonyl-CoA
and lactate, and possibly downstream CPT-I other mito-
chondrial enzymes such as Acyl-CoA synthase and elec-
tron transport chain. All these steps are sensitive to the
rate of CHO oxidation and thus a rise in CHO oxidation
seems to depress lipid oxidation despite availability of
fat and presence of all the enzymes of fat oxidation. Con-
versely, glycogen depletion reverses this inhibition and
increases fat oxidation, as observed during long duration
glycogen-depleting exercise.
These processes are under the influence of the central
nervous system and circulating hormones [see review in
(35)]. More specifically the level of maximal oxidation of
lipids is related to hormonal regulators: norepinephrine,
whose training induced changes are correlated to an im-
provement in LIPOXmax, and GH, whose deficit de-
creases it, a defect that can be reversed by GH replace-
ment (35). Downstream GH, IGF-I has also been report-
ed to be correlated to LIPOXmax, reflecting either a par-
allel effect of training on muscle fuel partitioning and IGF-
I release, or an action of IGF-I (or GH via IGF) on muscu-
lar lipid oxidation (36).
Other endocrine axes are surely also involved, but this
issue is poorly known and remains to be studied.
EXERCISE INDIRECT CALORIMETRY
After the development of a wide body of knowledge
during the last two decades of the XX century, the bal-
ance of substrates during exercise has been well de-
scribed and summarized with the classic picture of
Brooks and Mercier’s “crossover concept” (31). The
“crossover concept” implies that although increasing
exercise intensity results in a preferential use of CHO,
endurance training (ET) shifts the balance of substrates
during exercise toward a stronger reliance upon lipids.
The idea of developing a simple reliable exercise-test
for assessing this balance of substrates thus emerged
as a logical consequence of these fundamental studies
(23-25).
According to the teams, there are quite various proto-
cols, although on the average they yielded similar results.
However, some discrepancies among authors, for exam-
ple concerning the existence or not of a decrease in lipid
oxidation in diabetes (36) may be related to method-
ological differences.
Methodology has been reviewed elsewhere (23-25, 35-
36). The basic assumption that underlies exercise indi-
rect calorimetry is that blood lactate generation during
exercise has minimal influence on respiratory exchange
ratio (RER) after 3-4 min of exercise performed at a steady

During exercise Post-exercise

predictible by calorimetry compensatory rise
maximal at the not constant,
LIPOXmax/FATmax sometimes quite reduced

Fig. 1 - Effects of exercise on lipid oxida-

When exercise is prolonged >45 min
gradual shift to lipid oxidation when
glycogen depletion develops
Decrease in resting RER
after prolonged training
increased lipid oxidation at rest
tion: exercise may increase the oxidative
use of lipids by at least 4 mechanisms
[see (35) and (36)]. LIPOXmax: point of
maximal lipid oxidation; FATmax: maxi-
mal lipid oxidation at exercise; ; RER: res-
piratory exchange ratio.

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