S114
Role of Lipids on Endurance Capacity in Man C. Y Guezennec CERMA: CEV, Brétigny sur Orge, France
C. Y. Guezennec, Role of Lipids on Endurance Capacity in Man. mi Sports Med, Vol 13, Suppl l,ppSll4—S1l8, 1992.
A man whose weight is near 70 kg has approximately 15 kg of fat as triglycerides in adipose tissue, representing about 140,000 kcal. With such a quantity of stored fat, the question is to know why triglycerides are not the only fuelfor exercise. Probably because this fuel cannot sustain maximal rates of exercise. The ability to sustain maximal exercise is dependent on carbohydrate use. The reason for the limited rate at which energy can be derived from fat store is not clear. We can examine successively:
1) The rate of release from adipose tissue. Hy-
drolysis of the adipose tissue triglyceride is regulated by
hormonal and nervous influence. It has recently been shown that 70% of fatty acids released from adipose tissue at rest are reesterified. This value decreases to 25% at the onset of submaximal exercise at 40% of VO2max. One part of the increase in fat oxidation could therefore result from the reduced reesterification. 2) The capacity of transport and muscle extrac-
tion. A close correlation has been shown between the increase in FFA concentration and FFA uptake during increased energy expenditure under the effect of exercise. Ex-
ercise increases liprotein lipase (LPL) activity in muscle. This causes increase in muscle and cardiac FFA uptake and a decrease in LPL activity in adipose tissue. The control of
Introduction The fact that fat is utilized as a fuel by the exer-
cising human muscle was demonstrated by Christensen and Hensenin 1939(4). This initial finding was followed by numerous investigations which have evidenced the relationship between the storage of lipid in adipocyte and its utilization by muscles.
The important role of FFA in the transport of fuel from adipose tissue to muscle was identified. The mechanisms involved in peripheral tissue FFA extraction and oxidaInt.J.SportsMed. 13(I992)Sl 14—SI 18 GeorgThieme Verlag StuttgartNew York
this enzyme is coordinated by hormonal mechanisms resulting from the reduction of insulin and the increase in catecholamines induced by exercise. 3) The oxidative capacity of the muscle, During
heavy work carbohydrate fuel contributes to 80—90% of energy expenditure when the participation of lipid fuel is reduced to 10%. The regulation of this fuel selection could result from several factors capable of inhibiting fatty acid oxidation when glycolysis is elevated and, conversely, inhibiting glycolysis when FFA oxidation is elevated. The more detailed biochemical pathway is the inhibition of glycolysis when FFA oxidation is high. It is sustained by the concept of FFA glucose cycle of Randle (1963). The biochemical basis of this concept is that oxidation of FFA increases acetyl COA/COA ratio which inhibits pyruvate dehydrogenase, phosphofructokinase, and thus glycolysis. Also, the inhibition of FFA oxidation when glycolysis is high is regulated by the process of reesterification in the muscle.
Enhanced lipid availability resulting from eating a fatty meal before exercise, or a chronic high fat diet,
or fasting, is not capable of enhancing endurance capacity in humans. The glucose-fatty acid cycle which has previously been proposed to spare muscle glycogen stores is not operative in man. Key words
Physical exercise, lipid metabolism, lipid diet, endurance capacity, glucose, fatty acid cycle
tion were explained. All this research emphasizes the predominant role of lipid fuel to sustain prolonged exercise. But a question arises from these observations. Why are lipids such an important fuel for prolonged exercise? Several answers could be proposed. One could suggest an hypothesis based on the evo-
lutionary human adaptation to its primitive environment. Wahren (31) has demonstrated that lipid substrates are used in a similar way for energy expenditure in both fasting and prolonged exercise conditions.
The capacity to sustain prolonged fasting and physical exercise has probably conditioned the survival of primitive humans. The paleontologists describe primitive humans as a group of hunters-gatherers. One of the reasons of the success of human species was partially due to his ability to
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Abstract
mt. J. Sports Med. 13(1992) S115
Role ojLipids on Endurance Capacity in Man
follow game over long distances without feeding. Under such circumstances the crucial point for the group was the capacity of the pregnant women or young mothers to provide for the energy requirement of two organisms. The major role of lipid
fuel is further illustrated by the picture of the Hottentote venus. The perfect women in primitive environment are able to
store fat in order to subsequently utilize this fuel for fasting, walking and breast-feeding. The choice of lipid as fuel was probably developed by the simple fact that it provides more calories, with less weight, than carbohydrate or protein. The energy obtained from the oxidation of one gram of stored fat is double the energy that can be obtained from the oxidation of
enhanced by training. The biochemical alteration enhancing lipolytic response in the exercise trained state is thought to occur in protein kinase or hormone sensitive lipase (3, 13). The maximal lipolytic response to hormonal stimuli thus does not seem responsible for the limitation of lipid release. Another factor is involved in the control of the net flux of fatty acids in response to exercise: the triglyceride fatty acid cycle. In this cycle, fatty acids released during lipolysis within adipocytes are reesterified rather than released for oxidation. Exercise increases LPL activity in muscle, enhances muscle and cardiac FFA uptake, and decreases LPL
one gram of glycogen. Fat is the body's principal form of
activity in adipose tissue (19, 15). The control of this enzyme is
stored energy. A man whose weight is 70 kg has approximately
coordinated by hormonal mechanisms such as the reduction of insulin and the increase in catecholamines induced by exer-
15 kg of fat as triglycerides stored in adipose tissue representing about 140,000 kcal. In addition, intramuscular trigly-
cise.
cerides amount approximately 300 g. The energy stored in the months of fasting or to run approximatively 30 marathons. With such a large fat store, the question is why triglycerides are not the only fuelfor exercise. Probably because this fuel cannot sustain maximal rates of exercise. The ability to sustain maximal exercise is dependent on the use of carbohydrates. The reason for the limited rate at which energy can be
derived from fat store is not clear. We can examine successively:
I) the rate of release from adipose tissue, 2) the capacity of transport and muscle extraction, 3) the oxidative capacity of the muscle.
1) The rate of release from adipose tissue Hydrolysis of the adipose tissue triglyceride is regulated by hormonal nervous influence and adipocyte metabolism. It has recently been shown that 70% of released fatty acids are reesterified at rest. This value decreases to 25 % at the onset of submaximal exercise at 40% of VO2max. One part of
the increase in fat oxidation could thus result from the decrease in reesterification (32). But at higher exercise rates there is a decrease in rate of appearance of FFA (12). This inhibition of FFA release could be attributed to a high fractional reesterification rate in the adipose tissue during heavy exercise. This limitation of FFA release supports the concept that the supply of FFA from adipose tissue is a major factor limiting fat oxidation during exercise.
2) The capacity of transport and muscle extraction A close correlation has been shown between increases in plasma FFA concentration and FFA uptake during
exercise (20). But the FFA are transported in the form of triglyceride in circulating chylomicron and bound to very low density lipoprotein. Lipoprotein lipase is the capillary bound enzyme which hydrolyses the triglyceride in blood, making FFA available for uptake by muscles and other tissues. It acts by the way of norepinephrine released at sympathetic nerve endings, which activates the adenyl cyclase system to form increased amounts of AMPc. But other hormones play an additive role, enhancing lipolysis such as glucagon and growth hormone. The lipolytic response to neurohormonal stimulation is
The capacity of FFA extraction from the blood by the muscle cells seems not to be rate limiting for FFA oxidation during exercise.
3) The oxidative capacity of the muscle The work of Paul and Issekutz (21) has shown that the uptake of FFA increases with the increases in energy expenditure during exercise but the percent of FFA oxidized increases until a maximum before heavy exercise and thereafter decreases.
During heavy work carbohydrate fuel contributes to 80—90% of energy expenditure when the participation of lipid fuel is reduced to 10%. The regulation of this fuel selec-
tion could result from several factors capable of inhibiting fatty acid oxidation when glycolysis is elevated and conversely of inhibiting glycolysis when FFA oxidation is elevated. The
more detailed biochemical pathway is the inhibition of glycolysis when FFA oxidation is high. It is supported by the con-
cept of FFA glucose-cycle of Randle (22). The biochemical basis of this concept is that oxidation of FFA increases acetyl COA/COA ratio which inhibits pyruvate dehydrogenase. The increase in muscle citrate concentration derived from acetyl COA production inhibits phosphofructokinase and thus glycolysis. Moreover, the inhibition of FFA oxidation when glycolysis is high is regulated by the process of reesterification in the muscle.
At heavy work more fatty acids are taken up than oxidized. This finding supports the concept that part of
FFA is not directly oxidized but is incorporated into the muscle triglycerides (TG) pool (33). Increasing lactate production could inhibit FFA oxidation and favour FA reesterification.
The reciprocal inhibition of FFA and glucose oxidation is a very attractive hypothesis which could explain
muscle fuel selection in relation with exercise intensity. During prolonged exercise, the elevated FFA concentration might have a sparing effect on the muscular glycogen utilization. During intense exercise, high energy turnover inhibits FFA oxidation. The contribution of these biochemical mechanisms during exercise in humans is discussed. The operation of glucose FFA cycle of Randle (22) has been confirmed in animal experiments in the heart and in isolated soleus from mice
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body's triglyceride depots is enough to survive during 2
S116 mt. J. Sports Med. 13(1992)
C. Y Guezennec
[FFA J mM 0 1800 kcaL'day
Fig. 1 Free fatty acids plasma concen-
I—S-—f-—S—-I
tration at rest during a commando raid in a mountain environment with three levels of
o 3200 kcaL/day
caloric diet. 5: significant difference between groups of various caloric diet.
4300 kcal/day
1.0-
OSØ 1
Thursday
Wednesday
FrIøay
Fig. 2 Aerobic power before (Bef.) and
AEROBIC POWER
Watts
after (Aft.) a commando raid with three levels of caloric diet (1800, 3200 and 4300 kcal/day). s: significant difference between before and after the raid.
400
I—NS——I
300
200 Bet.
Aft. 1800
Bet,
Aft. 3200
and rats. Rat cardiac muscle seems very sensitive to the availa-
Bet,
Aft.
4300
bility of FFA. It has been shown that cardiac glycogen is
concentration is associated with a decrease in ATP/ADP + Pi ratio without any concomittant decrease in respiratory rate.
poorly utilized during prolonged exercise (29, 1, 8) and that an overcompensation occurs during recovery. On one hand, the suppression of FFA release by nicotinic acid produces a fall in
These data obtained during prolonged exercise at altitude could be extended to explain fuel regulation
cardiac glycogen level (29, 1); on the other hand, in spite of high blood FFA concentration, cardiac glycogen is greatly reduced after prolonged exercise in hypoxia (8). These findings evidence the fact that FFA glucose cycle is operative in cardiac muscle of rodents during exercise and that 02 becomes rate limiting for FFA oxidation in altitude. The enhanced cardiac glycogen use is observed for exercise performed at an altitude
during heavy exercise at sea level. The decrease in muscle cell energy charge resulting of heavy exercise could directly inhibit FFA oxidation and stimulate glycolysis. These data evidence
of 5,000 m. Mitochondrial oxidation is better preserved for lower 02 partial pressure in ambient atmosphere than in 5,000 m altitude hypoxia. It could be suggested that such an exposure to altitude stimulated heart glycogenolysis independently from tissue oxygen consumption. This is supported by the
factors that limit prolonged exercise is the amount of glycogen stored in working muscles (31). It has also been found that an increased availability of FFA reduces the rate of muscle gycogen utilization during exercise and delays the onset of exhaus-
measurement of a heart arteriovenous difference at 4,375 m in
man, showing an enhanced carbohydrate metabolism and a decreased free fatty acid oxidation without signs of anaerobic metabolism (18).
Several factors, such as neurohormonal changes and/or a decrease in adenylate charge concentration,
may contribute to glycogenolysis stimulation. Adenylate changes may be predominant. A decrease in extracellular 02
that in the heart, if fatty acids and oxygen are supplied at a sufficient rate to supply energy from fatty acid oxidation, glycogen and glucose utilization could be reduced or almost suppressed (22). Previous studies have shown that one of the
tioninrats(ll, 17,24). However, Decombaz et al. (6) and Satabin et al. (25) have observed an effect of feeding with medium chain triglyceride or long chain triglyceride on lipid and carbohy-
drate oxidation during prolonged submaximal exercise in man. Ravussin et al. (23) have used an intralipid infusion and heparin injection simultaneously during 2.5 h of exercise at 50% of VO2max. In spite of very high blood FFA level, the enhanced lipid availability did not alter the relative contribution
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Monday
mt. J. Sports Med. 13(1992) S117
Pole ofLiids on Endurance Capacity in Man
cise (> 1 h) rule out a physiological significance of Randle cycle in skeletal muscle.
These data can be used to compare the different responses between man and rat to an acute lipid availability before exercise. This difference could be illustrated by their respective tolerance to fasting. Dohm et a!. (7) have extended the glycogen sparing effect of increased FFA to fasting. It has been demonstrated that short term fasting in rat which produces lipolysis enhances endurance performance (7, 14). But the subsequent studies performed in human failed to evidence enhanced performance after short term fasting (16). A study was conducted during a commando raid to understand the relationship between caloric intake nad muscular work capacity (10). Twenty six male subjects were divided into three groups. Every group received a specific caloric intake: respectively 1,800 kcal/24 h, 3,200 kcal/24 h and 4,300 kcal/24 h. All subjects participated in a 5 day commando raid, they walked 30 km per day carrying an 11 kg load associated with military ex-
ercises. Venous blood samples were taken before the raid, twice during the raid and once after the raid. Two exercise tests
on a bicycle ergometer were performed before and after the raid in order to determine the VO2max and the anaerobic power. Metabolic results of venous blood demonstrated biological signs of undernutrition in the group receiving 1,800 kcal/24 h associating hypoinsulinemia, an increase in the circulating free fatty acids (Fig. 1) and in ketone bodies. The results of the aerobic and anaerobic power tests showed a significant decrease in the physical capacity in both fields (Fig. 2).
The experimental data show a decrease in mechanical performance when the total deficit, between physical expenditure
and food intake during 5 days, is between 5,000 and 10,000 kcal, in spite of enhanced FFA availability which increases with the caloric deficit.
Less data are available in man on the effect of chronic high fat diet on performance. Results obtained in man during prolonged physical exercise showed rapid and significant metabolization of medium chain triglycerides. These data
increases glycerol and ketone bodies concentrations in blood. The maximal aerobic capacity and anaerobic tests performed before and after the experiment revealed unchanged aerobic
capacity and anaerobic performance whatever the diet. Chronic high fat diet enhances the performance in rat (17, 28),
by numerous mechanisms. In rat, chronic high fat diet increases aerobic enzyme activities in the skeletal muscle (28), and increases hepatic neoglucogenesis (26, 27). High fat diet decreases liver glycogen before exercise; but the rats fed with high fat diet are able to maintain high blood glucose by increasing neoglucogenesis as evidenced by the increase in phosphoenol pyruvate carboxykinase activity, AMPc level, and the decrease in the fructose 2—6 phosphate level in liver (26, 27). Such an adaptation could also be observed with high protein diet. Thus, the major factor for enhancing liver neoglucogenesis seems to be carbohydrate deprivation (27).
Improved performance after high fat diet could be partially attributed to enhanced neoglucogenesis. It has been shown that the flux through neoglucogenesis is limiting for the capacity of endurance (31). One consequence of the increase in neoglucogenesis after high fat diet is an im-
provement of glycogen resynthesis after exercise. After chronic high fat diet glucose feeding during recovery evidences muscle glycogen overcompensation in rats (27). This could be explained by studies which suggest that high liver neoglucogenesis is more efficient for muscle glycogen resynthesis (30). Elsewhere, the low muscle glycogen content that results of a high fat diet is associated with an increased rate of glucose transport into the muscle in addition to an increased capacity to dispose of glucose by conversion to glycogen due to a greater glycogen synthase activity. Adaptation to high fat diet seems to improve endurance capacity in rats, but it is questionable whether this effect could be reproducible in man. Also, prolonged high fat diet presents several epidemiological risks which rule out the indication of such diet to improve performance in man.
In conclusion, the enhanced lipid availability obtained with a single fat meal before exercise, or with chronic high fat diet, or with fasting is not able to enhance endurance capacity in man. The glucose-fatty acids cycle which has previously been proposed for sparing muscle glycogen store is not operative in man. Elsewhere, for biochemical reasons, maximal energy production from lipolysis is not able to cover the energy expenditure during heavy exercise.
References
prompted the idea of incorporating such compounds into energetic complements entering the composition of combat and survival food kits. In order to consider the effects of these nutriments during real use, an experiment was carried out on 30 trained subjects, most of them were in the 7th Bataillon de Chasseurs Alpins (9). These subjects completed a typical mission including a 3-day raid on skis at 2,000—3,000 m altitude at
60% VO2max. The measurement of energetic expenditure by continuous recording of heart rate suggested an expenditure of 7,000—8,000 kcal/24 h. Subjects were divided into four groups in order to compare the metabolic effects of four different energetic supplements: one enriched with medium chain triglycerides, one enriched with long-chain triglycerides and two carbohydrate supplements. Results show that lipid supply
2
Conlee R. K., Dalsky G. P., Robinson K. C.: The influence of free fatty acids on glycogen recovery in rat heart after exercise. Eur J ApplPhysiol47:377—383, 1981. Costill D. L., Coyle E., Daisky G. P., Evans W., Furk W., Hooper D.: Effect of elevated plasma FFA and insulin on muscle glycogen usage during exercise. JAppIPhysiol43: 695—699, 1977.
Crampes F., Beauville M., Rivieres D., Garrigues M.: Effect of physical training in humans on the response of isolated fat cells to epinephrine. JApplPhysiol6 1:25—29, 1986.
Christensen E. H., Hansen 0.: Arbeitsfähigkeit und Ernahrung. SkandArchPhysiol8l: 150—171,1939. Cuendet G. S., Loten E. G., Renold A. E.: Evidence that the glucose fatty acid cycle is operative in isolated (soleus) muscle. Diabetologia 12: 336, 1975. Decombaz J., Arnaud M. H., Milon H., Moesch H., Plulipossian G., Tehlin A. L., Howald H.: Energy metabolism of medium chain
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of carbohydrate on lipid oxidation to the total energy expenditure. These works support the fact that the increase in plasma FFA does not decrease carbohydrate oxidation in man during prolonged exercise. In contrast, Costill et a!. (2) have observed a decrease in carbohydrate oxidation and in muscle glycogen use during 30 mm. of exercise at 70% of VO2max after a fatty meal. Several factors may account for these different results; a high rate of glycolysis during short term exercise could be ideal for FFA to exhibit an inhibiting action on glucose uptake and oxidation. The data obtained on man during prolonged exer-
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Dohm G. L., Tapscott E. B., Barakat M. A., Kasperek G. J.: Influence of fasting on glycogen depletion in rats during exercise. J ApplPhysiol55:830—833, 1983. Guezennec C. Y., Satabin P., Serrurier B.: Influence d'une restric-
tion calorique et de la prise de complements énergétiques lipidiques ou glucidiques sur Ia réponse métabolique et hormonale au cours d'un raid a ski alpin. Rapport CERMA 86—40, 1986.
10 Guezennec C. Y., Satabin P., Legrand H.: Role de l'apport calorique sur la capacité a réaliser des efforts physiques intenses et soutenus. Rapport CERMA 87—32, 1987. I! Hickson R. C., Rennie M. J., Conlee R. J., Winder W. W., Holloszy J. 0.: Effect of increased plasma fatty acids on glycogen utilization andendurance.JApplPhysiol43: 829—833, 1977. 12 Hodgetts V., Coppack S. W., Frayn K. N. J., Hockaday D. R.: Fac-
tors controlling fat mobilization from human subcutaneous adipose tissue during exercise. JApp!Physiol7 1:445—451, 1991. 3 Izawa T., Kombayashi T., Mochizuki T., Suda K., Tsuboi M.: Enhanced coupling of adenylate cyclase to lipolysis in permeabilized adipocytes from trained rats. JApplPhysiol7 1:23—29, 1991. 14 Koubi H. E., Desplanches D., Gabrielle C., Cortet-Emard J. M., Sempore B., Favier R. J.: Exercise endurance and fuel utilization: a reevaluation of the effects of fasting. J App! Physiol 30: 1337— 1342, 1991.
15 Ladu M. J., Kapsas H., Palmer W. K.: Regulation of lipoprotein lipase in muscle and adipose tissue during exercise. JAppi Physiol 71:404—409, 1991.
16 Maughan R. J., Gleeson M.: Influence of a 36 h fast followed by refeeding with glucose, glycerol or placebo on metabolism and performance during prolonged exercise in man. Eur JAppiPhysiol 57:570—576,1988. 17 Miller W. C., Bryce G. R., Conlee R. K.: Adaptations to a high fat diet that increases exercise endurance in male rats. J App! Physiol 56:78—83,1984.
8 Moret P. R.: Coronary blood flow and myocardial metabolism in
man at high altitude. In: High altitude physiology. Porter R., Knoght J. 8eds). Edinburgh and London, Churchill livingston l99l,pp 131—144. 19 Nikkila F. A.: Role of lipoprotein lipase in metabolic adaptation
to exercise and training. In: Lipoprotein lipase. Ed. by J.
20
Borewztakn chicago II Evena: 1987, pp 187—199. Paul P.: Uptake and oxidation of substrates in intact animal during
exercise. Ed. by Pernow B. and Saltin B.: Muscle metabolism during exercise. Press New-York: 1971, pp 225—247.
21 Paul P., Issekutz B.: Role of extra muscular energy sources in the metabolism of exercising dogs. JAppIPhysiol22: 615—622, 1971.
22 Randle P. J., Garland P. B., Males C. N., Newsholmes E. A.: The glucose fatty acid cycle; its role in insulin sensitivity and metabolic disturbances of diabetes mellitus. Lancet 1: 185—189, 1963.
23 Ravussin E., Bogardus E., Scheidegger K., Lagrange B., Horton E., Horton E. S.: Effect of elevated FFA on carbohydrate and lipid oxidation during prolonged exercise in humans. JAppiPhysiol 60: 893 —900, 1986.
24 Rennie M. J., Winder W. W., Hollszy J. 0.: A sparing effect of increased plasma fatty acids on muscle and liver glycogen content in theexercisingrat.BiochemJ56: 156—157,1976. 25 Satabin P., Portero P., Defer G., Bricout J., Guezennec C. Y.: Metabolic and hormonal responses to lipid and carbohydrate diets during exercise in man. Med Sci Sports Exerc 19:218—223, 1987. 26 Satabin P., Bois-Joyeux B., Chanez M., Guezennec C. Y., Peret J.: Effects of long term feeding of high protein or high fat diets on the responses to exercise in the rat. Eur JAppl Physiol 58: 583—590, 1989.
27 Satabin P., Bois-Joyeux B., Chanez M., Guezennec C. Y., Peret J.: Post-exercise glycogen resynthesis in trained high protein or high fat fed rats after glucose feeding. Eur JAppiPhysiol 58: 591—595, 1989.
28 Simi B., Sempore B., Mayet M. M., Favier R. J.: Additive effects of training and hIgh fat diet on energy metabolism during exercise. J ApplPhysiol7l: 197—203,1991. 29 Stankiewciz-Chroszucha B., Gorski K.: Effect of substrate supply and 3-adrenergic blockade on heart glycogen and triglyceride utilization during exercise in the rat. EurJApplPhysiol43: 11—14, 1980.
30 Stevenson R. W., Mitchell D. R., Hendrik K. K., Rainey R., Charrington A. D., Frizzel R. T.: Lactate as substrate for glycogen resynthesis after exercise. JApplPhysiol62: 2237—2240, 1987. 31 Wahren J.: Metabolic adaptation to physical exercise in man. In: Endocrinology De Groot J. (ed). Grune and Stratton: 1979, 1911— 1926. 32 Wolfe R. R., Klein S., Carraro F., Weber J. N.: Role of triglyceridefatty acid cycle in controlling fat metabolism in humans during and afterexercise.AmJPhysiol258: 382—389, 1980. Zierler K. L.: Fatty acids as substrate for heart and skeletal muscle. A. MA. Manager 54: 35—39,1977. C. Y Guezennec
CERMA: CEV F-9 1228 Brétigny sur Orge
France
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triglycerides versus carbohydrate during exercise. Eur JAppi Phys-
C. Y. Guezennec
Role of Lipids on Endurance Capacity in Man C. Y Guezennec CERMA: CEV, Brétigny sur Orge, France
C. Y. Guezennec, Role of Lipids on Endurance Capacity in Man. mi Sports Med, Vol 13, Suppl l,ppSll4—S1l8, 1992.
A man whose weight is near 70 kg has approximately 15 kg of fat as triglycerides in adipose tissue, representing about 140,000 kcal. With such a quantity of stored fat, the question is to know why triglycerides are not the only fuelfor exercise. Probably because this fuel cannot sustain maximal rates of exercise. The ability to sustain maximal exercise is dependent on carbohydrate use. The reason for the limited rate at which energy can be derived from fat store is not clear. We can examine successively:
1) The rate of release from adipose tissue. Hy-
drolysis of the adipose tissue triglyceride is regulated by
hormonal and nervous influence. It has recently been shown that 70% of fatty acids released from adipose tissue at rest are reesterified. This value decreases to 25% at the onset of submaximal exercise at 40% of VO2max. One part of the increase in fat oxidation could therefore result from the reduced reesterification. 2) The capacity of transport and muscle extrac-
tion. A close correlation has been shown between the increase in FFA concentration and FFA uptake during increased energy expenditure under the effect of exercise. Ex-
ercise increases liprotein lipase (LPL) activity in muscle. This causes increase in muscle and cardiac FFA uptake and a decrease in LPL activity in adipose tissue. The control of
Introduction The fact that fat is utilized as a fuel by the exer-
cising human muscle was demonstrated by Christensen and Hensenin 1939(4). This initial finding was followed by numerous investigations which have evidenced the relationship between the storage of lipid in adipocyte and its utilization by muscles.
The important role of FFA in the transport of fuel from adipose tissue to muscle was identified. The mechanisms involved in peripheral tissue FFA extraction and oxidaInt.J.SportsMed. 13(I992)Sl 14—SI 18 GeorgThieme Verlag StuttgartNew York
this enzyme is coordinated by hormonal mechanisms resulting from the reduction of insulin and the increase in catecholamines induced by exercise. 3) The oxidative capacity of the muscle, During
heavy work carbohydrate fuel contributes to 80—90% of energy expenditure when the participation of lipid fuel is reduced to 10%. The regulation of this fuel selection could result from several factors capable of inhibiting fatty acid oxidation when glycolysis is elevated and, conversely, inhibiting glycolysis when FFA oxidation is elevated. The more detailed biochemical pathway is the inhibition of glycolysis when FFA oxidation is high. It is sustained by the concept of FFA glucose cycle of Randle (1963). The biochemical basis of this concept is that oxidation of FFA increases acetyl COA/COA ratio which inhibits pyruvate dehydrogenase, phosphofructokinase, and thus glycolysis. Also, the inhibition of FFA oxidation when glycolysis is high is regulated by the process of reesterification in the muscle.
Enhanced lipid availability resulting from eating a fatty meal before exercise, or a chronic high fat diet,
or fasting, is not capable of enhancing endurance capacity in humans. The glucose-fatty acid cycle which has previously been proposed to spare muscle glycogen stores is not operative in man. Key words
Physical exercise, lipid metabolism, lipid diet, endurance capacity, glucose, fatty acid cycle
tion were explained. All this research emphasizes the predominant role of lipid fuel to sustain prolonged exercise. But a question arises from these observations. Why are lipids such an important fuel for prolonged exercise? Several answers could be proposed. One could suggest an hypothesis based on the evo-
lutionary human adaptation to its primitive environment. Wahren (31) has demonstrated that lipid substrates are used in a similar way for energy expenditure in both fasting and prolonged exercise conditions.
The capacity to sustain prolonged fasting and physical exercise has probably conditioned the survival of primitive humans. The paleontologists describe primitive humans as a group of hunters-gatherers. One of the reasons of the success of human species was partially due to his ability to
Downloaded by: Universite Laval. Copyrighted material.
Abstract
mt. J. Sports Med. 13(1992) S115
Role ojLipids on Endurance Capacity in Man
follow game over long distances without feeding. Under such circumstances the crucial point for the group was the capacity of the pregnant women or young mothers to provide for the energy requirement of two organisms. The major role of lipid
fuel is further illustrated by the picture of the Hottentote venus. The perfect women in primitive environment are able to
store fat in order to subsequently utilize this fuel for fasting, walking and breast-feeding. The choice of lipid as fuel was probably developed by the simple fact that it provides more calories, with less weight, than carbohydrate or protein. The energy obtained from the oxidation of one gram of stored fat is double the energy that can be obtained from the oxidation of
enhanced by training. The biochemical alteration enhancing lipolytic response in the exercise trained state is thought to occur in protein kinase or hormone sensitive lipase (3, 13). The maximal lipolytic response to hormonal stimuli thus does not seem responsible for the limitation of lipid release. Another factor is involved in the control of the net flux of fatty acids in response to exercise: the triglyceride fatty acid cycle. In this cycle, fatty acids released during lipolysis within adipocytes are reesterified rather than released for oxidation. Exercise increases LPL activity in muscle, enhances muscle and cardiac FFA uptake, and decreases LPL
one gram of glycogen. Fat is the body's principal form of
activity in adipose tissue (19, 15). The control of this enzyme is
stored energy. A man whose weight is 70 kg has approximately
coordinated by hormonal mechanisms such as the reduction of insulin and the increase in catecholamines induced by exer-
15 kg of fat as triglycerides stored in adipose tissue representing about 140,000 kcal. In addition, intramuscular trigly-
cise.
cerides amount approximately 300 g. The energy stored in the months of fasting or to run approximatively 30 marathons. With such a large fat store, the question is why triglycerides are not the only fuelfor exercise. Probably because this fuel cannot sustain maximal rates of exercise. The ability to sustain maximal exercise is dependent on the use of carbohydrates. The reason for the limited rate at which energy can be
derived from fat store is not clear. We can examine successively:
I) the rate of release from adipose tissue, 2) the capacity of transport and muscle extraction, 3) the oxidative capacity of the muscle.
1) The rate of release from adipose tissue Hydrolysis of the adipose tissue triglyceride is regulated by hormonal nervous influence and adipocyte metabolism. It has recently been shown that 70% of released fatty acids are reesterified at rest. This value decreases to 25 % at the onset of submaximal exercise at 40% of VO2max. One part of
the increase in fat oxidation could thus result from the decrease in reesterification (32). But at higher exercise rates there is a decrease in rate of appearance of FFA (12). This inhibition of FFA release could be attributed to a high fractional reesterification rate in the adipose tissue during heavy exercise. This limitation of FFA release supports the concept that the supply of FFA from adipose tissue is a major factor limiting fat oxidation during exercise.
2) The capacity of transport and muscle extraction A close correlation has been shown between increases in plasma FFA concentration and FFA uptake during
exercise (20). But the FFA are transported in the form of triglyceride in circulating chylomicron and bound to very low density lipoprotein. Lipoprotein lipase is the capillary bound enzyme which hydrolyses the triglyceride in blood, making FFA available for uptake by muscles and other tissues. It acts by the way of norepinephrine released at sympathetic nerve endings, which activates the adenyl cyclase system to form increased amounts of AMPc. But other hormones play an additive role, enhancing lipolysis such as glucagon and growth hormone. The lipolytic response to neurohormonal stimulation is
The capacity of FFA extraction from the blood by the muscle cells seems not to be rate limiting for FFA oxidation during exercise.
3) The oxidative capacity of the muscle The work of Paul and Issekutz (21) has shown that the uptake of FFA increases with the increases in energy expenditure during exercise but the percent of FFA oxidized increases until a maximum before heavy exercise and thereafter decreases.
During heavy work carbohydrate fuel contributes to 80—90% of energy expenditure when the participation of lipid fuel is reduced to 10%. The regulation of this fuel selec-
tion could result from several factors capable of inhibiting fatty acid oxidation when glycolysis is elevated and conversely of inhibiting glycolysis when FFA oxidation is elevated. The
more detailed biochemical pathway is the inhibition of glycolysis when FFA oxidation is high. It is supported by the con-
cept of FFA glucose-cycle of Randle (22). The biochemical basis of this concept is that oxidation of FFA increases acetyl COA/COA ratio which inhibits pyruvate dehydrogenase. The increase in muscle citrate concentration derived from acetyl COA production inhibits phosphofructokinase and thus glycolysis. Moreover, the inhibition of FFA oxidation when glycolysis is high is regulated by the process of reesterification in the muscle.
At heavy work more fatty acids are taken up than oxidized. This finding supports the concept that part of
FFA is not directly oxidized but is incorporated into the muscle triglycerides (TG) pool (33). Increasing lactate production could inhibit FFA oxidation and favour FA reesterification.
The reciprocal inhibition of FFA and glucose oxidation is a very attractive hypothesis which could explain
muscle fuel selection in relation with exercise intensity. During prolonged exercise, the elevated FFA concentration might have a sparing effect on the muscular glycogen utilization. During intense exercise, high energy turnover inhibits FFA oxidation. The contribution of these biochemical mechanisms during exercise in humans is discussed. The operation of glucose FFA cycle of Randle (22) has been confirmed in animal experiments in the heart and in isolated soleus from mice
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body's triglyceride depots is enough to survive during 2
S116 mt. J. Sports Med. 13(1992)
C. Y Guezennec
[FFA J mM 0 1800 kcaL'day
Fig. 1 Free fatty acids plasma concen-
I—S-—f-—S—-I
tration at rest during a commando raid in a mountain environment with three levels of
o 3200 kcaL/day
caloric diet. 5: significant difference between groups of various caloric diet.
4300 kcal/day
1.0-
OSØ 1
Thursday
Wednesday
FrIøay
Fig. 2 Aerobic power before (Bef.) and
AEROBIC POWER
Watts
after (Aft.) a commando raid with three levels of caloric diet (1800, 3200 and 4300 kcal/day). s: significant difference between before and after the raid.
400
I—NS——I
300
200 Bet.
Aft. 1800
Bet,
Aft. 3200
and rats. Rat cardiac muscle seems very sensitive to the availa-
Bet,
Aft.
4300
bility of FFA. It has been shown that cardiac glycogen is
concentration is associated with a decrease in ATP/ADP + Pi ratio without any concomittant decrease in respiratory rate.
poorly utilized during prolonged exercise (29, 1, 8) and that an overcompensation occurs during recovery. On one hand, the suppression of FFA release by nicotinic acid produces a fall in
These data obtained during prolonged exercise at altitude could be extended to explain fuel regulation
cardiac glycogen level (29, 1); on the other hand, in spite of high blood FFA concentration, cardiac glycogen is greatly reduced after prolonged exercise in hypoxia (8). These findings evidence the fact that FFA glucose cycle is operative in cardiac muscle of rodents during exercise and that 02 becomes rate limiting for FFA oxidation in altitude. The enhanced cardiac glycogen use is observed for exercise performed at an altitude
during heavy exercise at sea level. The decrease in muscle cell energy charge resulting of heavy exercise could directly inhibit FFA oxidation and stimulate glycolysis. These data evidence
of 5,000 m. Mitochondrial oxidation is better preserved for lower 02 partial pressure in ambient atmosphere than in 5,000 m altitude hypoxia. It could be suggested that such an exposure to altitude stimulated heart glycogenolysis independently from tissue oxygen consumption. This is supported by the
factors that limit prolonged exercise is the amount of glycogen stored in working muscles (31). It has also been found that an increased availability of FFA reduces the rate of muscle gycogen utilization during exercise and delays the onset of exhaus-
measurement of a heart arteriovenous difference at 4,375 m in
man, showing an enhanced carbohydrate metabolism and a decreased free fatty acid oxidation without signs of anaerobic metabolism (18).
Several factors, such as neurohormonal changes and/or a decrease in adenylate charge concentration,
may contribute to glycogenolysis stimulation. Adenylate changes may be predominant. A decrease in extracellular 02
that in the heart, if fatty acids and oxygen are supplied at a sufficient rate to supply energy from fatty acid oxidation, glycogen and glucose utilization could be reduced or almost suppressed (22). Previous studies have shown that one of the
tioninrats(ll, 17,24). However, Decombaz et al. (6) and Satabin et al. (25) have observed an effect of feeding with medium chain triglyceride or long chain triglyceride on lipid and carbohy-
drate oxidation during prolonged submaximal exercise in man. Ravussin et al. (23) have used an intralipid infusion and heparin injection simultaneously during 2.5 h of exercise at 50% of VO2max. In spite of very high blood FFA level, the enhanced lipid availability did not alter the relative contribution
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Monday
mt. J. Sports Med. 13(1992) S117
Pole ofLiids on Endurance Capacity in Man
cise (> 1 h) rule out a physiological significance of Randle cycle in skeletal muscle.
These data can be used to compare the different responses between man and rat to an acute lipid availability before exercise. This difference could be illustrated by their respective tolerance to fasting. Dohm et a!. (7) have extended the glycogen sparing effect of increased FFA to fasting. It has been demonstrated that short term fasting in rat which produces lipolysis enhances endurance performance (7, 14). But the subsequent studies performed in human failed to evidence enhanced performance after short term fasting (16). A study was conducted during a commando raid to understand the relationship between caloric intake nad muscular work capacity (10). Twenty six male subjects were divided into three groups. Every group received a specific caloric intake: respectively 1,800 kcal/24 h, 3,200 kcal/24 h and 4,300 kcal/24 h. All subjects participated in a 5 day commando raid, they walked 30 km per day carrying an 11 kg load associated with military ex-
ercises. Venous blood samples were taken before the raid, twice during the raid and once after the raid. Two exercise tests
on a bicycle ergometer were performed before and after the raid in order to determine the VO2max and the anaerobic power. Metabolic results of venous blood demonstrated biological signs of undernutrition in the group receiving 1,800 kcal/24 h associating hypoinsulinemia, an increase in the circulating free fatty acids (Fig. 1) and in ketone bodies. The results of the aerobic and anaerobic power tests showed a significant decrease in the physical capacity in both fields (Fig. 2).
The experimental data show a decrease in mechanical performance when the total deficit, between physical expenditure
and food intake during 5 days, is between 5,000 and 10,000 kcal, in spite of enhanced FFA availability which increases with the caloric deficit.
Less data are available in man on the effect of chronic high fat diet on performance. Results obtained in man during prolonged physical exercise showed rapid and significant metabolization of medium chain triglycerides. These data
increases glycerol and ketone bodies concentrations in blood. The maximal aerobic capacity and anaerobic tests performed before and after the experiment revealed unchanged aerobic
capacity and anaerobic performance whatever the diet. Chronic high fat diet enhances the performance in rat (17, 28),
by numerous mechanisms. In rat, chronic high fat diet increases aerobic enzyme activities in the skeletal muscle (28), and increases hepatic neoglucogenesis (26, 27). High fat diet decreases liver glycogen before exercise; but the rats fed with high fat diet are able to maintain high blood glucose by increasing neoglucogenesis as evidenced by the increase in phosphoenol pyruvate carboxykinase activity, AMPc level, and the decrease in the fructose 2—6 phosphate level in liver (26, 27). Such an adaptation could also be observed with high protein diet. Thus, the major factor for enhancing liver neoglucogenesis seems to be carbohydrate deprivation (27).
Improved performance after high fat diet could be partially attributed to enhanced neoglucogenesis. It has been shown that the flux through neoglucogenesis is limiting for the capacity of endurance (31). One consequence of the increase in neoglucogenesis after high fat diet is an im-
provement of glycogen resynthesis after exercise. After chronic high fat diet glucose feeding during recovery evidences muscle glycogen overcompensation in rats (27). This could be explained by studies which suggest that high liver neoglucogenesis is more efficient for muscle glycogen resynthesis (30). Elsewhere, the low muscle glycogen content that results of a high fat diet is associated with an increased rate of glucose transport into the muscle in addition to an increased capacity to dispose of glucose by conversion to glycogen due to a greater glycogen synthase activity. Adaptation to high fat diet seems to improve endurance capacity in rats, but it is questionable whether this effect could be reproducible in man. Also, prolonged high fat diet presents several epidemiological risks which rule out the indication of such diet to improve performance in man.
In conclusion, the enhanced lipid availability obtained with a single fat meal before exercise, or with chronic high fat diet, or with fasting is not able to enhance endurance capacity in man. The glucose-fatty acids cycle which has previously been proposed for sparing muscle glycogen store is not operative in man. Elsewhere, for biochemical reasons, maximal energy production from lipolysis is not able to cover the energy expenditure during heavy exercise.
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