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- during exercise and improves body composition, lipid and in-
alized exercise training in obesity and diabetes, targeted at flammatory status, and glycated hemoglobin, thus repre-
the level of maximal lipid oxidation as can be determined by senting a possible future strategy for exercise prescription in
exercise calorimetry. This measurement is reproducible and patients suffering from obesity and diabetes.
reflects muscles’ ability to oxidize lipids. Targeted training at (J. Endocrinol. Invest. 35: 686-691, 2012)
this level is well tolerated, increases the ability to oxidize lipids ©2012, Editrice Kurtis

INTRODUCTION efficiency. Such a strategy will be the topic of this review,

Chronic physical inactivity is a well-established etiologi- which will focus on a concept of exercise prescription that
cal factor for many largely widespread diseases (1-4), in- generates a growing number of studies, the concept of
cluding obesity (5) and diabetes (6), whose course has maximal lipid oxidation during muscular activity.
been reported to be positively influenced by regular mus-
cular activity (7).
Based on this evidence, a recent editorial urges public THE CONCEPT OF “INDIVIDUALIZED TRAINING”
policy makers to consider structured exercise and phys- AND A PROPOSAL TO APPLY IT IN OBESITY
ical activity programs as worthy of insurance reimburse- AND DIABETES
ment to promote health, especially in high-risk popula- For training patients suffering from respiratory and heart
tions (8). Exercise is more efficient if structured, i.e., per- diseases, the “individualization concept”, has been pro-
formed after a precise prescription and with a serious posed. After an exercise-test, a specific level for each sub-
coaching and follow-up (9). ject is defined (in this case the ventilatory threshold). This
Guidelines for exercise prescription are regularly released approach has been reported to provide better results (15).
(7). In metabolic diseases it is mostly considered as a Recommendations for exercise in diabetes (6) and obesi-
method to induce an energy deficit (10), and duration of ty (16) refer only to a type of activity (endurance, resis-
exercise seems to be the major determinant of its effi- tance) and to an amount of energy deficit, with no refer-
ciency (11). ence to such an “individualization concept”.
Recent studies point out the potential interest of short Clearly, this energy deficit is a major determinant of the ef-
duration high-intensity exercise (12) which results in im- ficiency of exercise (10), but individual responsiveness to
portant improvements of muscle metabolism. However, exercise-induced fat loss seems to be improved by other
the variety of exercise that has accumulated the greatest factors. Among them there is the ability to oxidize lipids
body of evidence for its efficiency is endurance exercise at rest (17), and there is limited but growing evidence to
(13), which is easier to apply at low intensity in very suggest that the ability to oxidize lipids during exercise is
sedentary patients in whom strenuous exercise is poorly also a determinant of exercise-induced weight loss (18), as
tolerated and even potentially harmful (14). was postulated 10 years ago (19). Conversely, a greater re-
In order to obtain the best results with low-intensity ex- liance on carbohydrates (CHO), resulting in a negative
ercise, it is interesting to develop strategies to improve its 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
Key-words: Diabetes, exercise, fat oxidation, indirect calorimetry, obesity, physical increase their efficiency. Targeting exercise training at the
training, sedentariness.
level where lipid oxidation is maximal may represent such
Correspondence: J.-F. Brun, INSERM U1046, Département de Physiologie Clinique,
Equipe d’Exploration Métabolique (CERAMM), Hôpital Lapeyronie, 34295 Montpel-
a strategy. In addition, although this issue is beyond the
lier cedex 5 (France). scope of this review, it is clear that lipid accumulation in
E-mail: [email protected] adipose tissue, liver, and muscle represents a major ab-
Accepted May 30, 2012. normality in obesity and diabetes (21), and this is one more
First published online June 25, 2012. reason to target exercise on lipid oxidation.

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 Lipid oxidation during exercise

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

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

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