Metabolic Adaptations to Endurance Training: Increased Fat ...

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Metabolic Adaptations to Endurance Training: Increased Fat Oxidation

An Honors Thesis

by

Kindal A. Shores

Thesis Advisor: Jeff Valek, Ph.D.

Assistant Professor, School of Physical Education

Ball State University

Muncie, Indiana

December, 2000

- Acknowledgements

Many thanks are due to Jeff Volek, Ph.D., my thesis advisor, for his mentorship during this project.

He gave willingly of his resources, time, and knowledge to further my knowledge and experience.

Thank you Dr. Volek for your valuable and honest criticisms and for challenging me on this project.

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Abstract

Endurance exercise training elicits physiological adaptations within the body. One of the

adaptations observed with endurance training is the body's ability to oxidize increased amounts of

fat as energy during exercise. A critical role in this energy substrate shift is mediated by the

mitochondria. The mechanisms for adaptation at the mitochondria and their relative importance to

the energy substrate shift will be overviewed. Further, the role of changes in hormone

concentration will be discussed. These metabolic adaptations are two important mediators of the

energy substrate utilized for muscular activity after a program of endurance training.

Metabolic Adaptations to Endurance Training: Increased fat oxidation

Contents

1. INTRODUCTION .......................................................................................... 1 1.1 Importance ............................................................................................. 2 1.2 Experimental Models ................................................................................. 3

2. IMROVED MIDOCHONDRIAL RESPIRATION .................................................... 4 2.1 Mitochondrial Structure and function ............................................................ 5 2.2 Increased Mitochondrial Size and Number ............................................... , .... 6 2.3 Increase in Oxidative Enzymes ................................................................... 7 2.4 Effects of Mitochondrial Adaptations ............................................................ 8

2.4.1 Decreased cytosolic ADP as a metabolic regulator .................................. 8 2.4.2 Decreased accumulation of AMP ....................................................... 11 2.4.3 The possible role of malonyl CoA. ...................................................... 11

2.5 Correlation of Mitochondrial Adaptations and the Substrate Shift ...................... 12 2.5.1 Timecourse for adaptations ............................................................... 13

3. HORMONAL ADAPTATIONS ........................................................................... 13 3.1 The Nature of Hormones .......................................................................... 13 3.2 Catecholamine Response to Endurance Training .......................................... 14

3.2.1 Exercise response of the catecholamines ............................................. 15 3.2.2 Training effect on catecholamines ...................................................... 15 3.2.3 Significance of the training response ................................................... 16 3.2.4 Conflicting reports ........................................................................... 18

3.3 Insulin and Glucagon Responses to Endurance Training ................................ 19 3.3.1 Exercise responses of insulin and glucagon .......................................... 19 3.3.2 Insulin training response ................................................................... 20 3.3.3 Significance of the training response ................................................... 20 3.3.4 Glucagon training response ............................................................... 21

3.4 Cortisol Response to Endurance Training .................................................... 21 3.4.1 Exercise response of cortisoL ........................................................... 22 3.4.2 Training response of cortisol ............................................................. 22

3.5 Growth Hormone Response to Endurance Training ....................................... 23 3.5.1 Exercise response of the growth hormone ........................................... 23 3.5.2 Training response of growth hormone ................................................. 23

3.6 The Net Effect of Hormones in the Substrate Shift .............................................. 24

4. SOURCES OF INCREASED FAT FOR OXIDATION ............................................. 24 4.1 Intramuscular T riglycerides Fuel the Substrate Shift ....................................... 25 4.2 Increased Sensitivity to Plasma FFA fuels the Substrate Shift .......................... 25 4.3 Evidence of Increased Intramuscular Triglyceride Utilization ............................ 26

5. CONCLUSiON .............................................................................................. 26 -References ...................................................................................................... 28

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Metabolic Adaptations to Endurance Training: Increased fat oxidation

1. Introduction

Endurance training elicits profound adaptations in the physiology of the cardiovascular, endocrine,

and muscular systems. One important adaptation is an energy substrate shift observed in trained

humans. Energy substrates, carbohydrate, fat, and protein provide the fuel for muscular activity.

These substrates are used in different amounts in trained and untrained humans. Endurance

exercise training increases the oxidation of fat during submaximal exercise (Holloszy, 1973,

Henriksson, 1977, Jansson and Kaijser, 1987, Robergs and Roberts, 1997). Greatercapillarization

of muscle and improved oxygen uptake and delivery are also associated with endurance training.

These adaptations occur independently of the energy substrate shift (Holloszy, 1973}. Endurance

trained humans burn more relative fat to carbohydrate during exercise. This is true for exercise

performed at the same absolute intensity (Coggan, 1990; Green et aI., 1991; Hartley et al.; 1972)

and at the same relative intensity of maximal oxygen uptake (Jansson and Kaijser; 1987, Koivisto et

al. 1982; Moore et al. 1987; Turcotte et al. 1992). The mechanisms for this adaptation are unclear.

This review will overview the critical role of mitochondrial adaptations in mediating the substrate shift

observed with chronic endurance training. The role of hormone changes in hormone concentrations

in mediating substrate production and uptake and therefore, the energy substrate shift will also be

discussed .

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Metabolic Adaptations

1.1 Importance

The energy substrate shift procuring an increased reliance on lipid metabolism has important

implications for athletic performance. The goal of competitive endurance training is to enhance

performance by decreasing the time required to cover a given distance. Metabolic adaptations in

substrate utilization help achieve this goal.

Ignoring the contribution from amino acid oxidation in the muscle, carbohydrate and fat are the

primary fuels for muscle contraction. The shift to increased fat oxidation, the body's increased use of

fat for energy, causes a concurrent sparing of glycogen stores. Intensity of exercise is the primary

factor that dictates relative use of carbohydrate and fat. After training, the relative amount of fat

utilized increases at a given submaximal intensity. This allows glycogen (carbohydrate fuel) to be

spared. Glycogen depletion is associated with the onset of fatigue. (Jeukendrup et aI., 1998). The

increased use of fat as an energy substrate results in glycogen sparing and prolongs time to

exhaustion (Jeukendrup et al. 1998).

The shift of energy substrates from glycogen to fat has a biochemical advantage. Fat provides two

times the energy value of carbohydrates per gram. This makes fat a more efficient fuel per unit of

weight. The proportionate energy of fat to carbohydrate is evidenced by relative ATP production.

One mol of stearic acid, an 18 carbon saturated fatty acid, yields 146 ATP compared to 39 ATP

associated with the complete catabolism of one molecule of glucose (Jeunkendrup et aI., 1998).

1 mol glucose: C6H1206+ 602+ 39 ADP + 39 Pi7 6C02 + 6H20 + 39 ATP

1 mol stearic acid (fat): CH3 (CH2)16COOH+2602+146 ADP+146 Pi718C02+52H20+146 ATP

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While this shift to fat oxidation requires increased oxygen, other metabolic adaptations at the skeletal

muscle help to increase delivery and utilization of oxygen. Increased capillarization and

mitochondrial density in muscle allow the shift to fat oxidation that nets more energy for exercise.

The energy substrate shift from carbohydrate to fat slows fatigue and provides greater energy

production.

1.2 Experimental Models

This review will concentrate on human studies. These human studies were made possible by

preceding investigations with animals. The initial use of animals offered several advantages. Animal

studies allow the inbreeding of animals. This lowers intersubject variability and mitigates genetic

factors. Animal studies also offer the opportunity to perform invasive procedures not sanctioned in

human studies. Another advantage animal studies offer is the ease of training and deconditioning

enforcement. Subsequent human studies have provided advantages as well. Taking theory and

results from animal populations, human subjects were used to negate the difficulty of comparing

animal and human physiological systems and responses.

Two types of research have been used to examine metabolic adaptations to endurance training.

These include longitudinal and cross-sectional studies. Longitudinal studies examine one or more

groups before and after a given length of time. One advantage of longitudinal stUdies is that pre and

post testing of the same groups eliminates genetic confounds. Subjects serve as their own control in

this experimental model. One drawback of longitudinal studies is the need for long-term subject

adherence. In endurance training trials, subjects must adhere to an experimental intervention for

weeks, months, or longer. Longitudinal stUdies also require considerable time and financial

investment. Cross-sectional studies examine different groups of people at a single time point. This

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experimental design offers the advantages of time and cost efficiency. Data collection is also

simplified. One drawback of cross sectional studies is the role that undetected genetic factors play

in physiological responses. Both studies are valuable and will be utilized in this review.

Another important consideration in research studies that examine metabolic adaptations to training is

the selection of intensity used after training. Research models employ the use of both relative

versus same absolute intensities. In relative intensity studies, a subject will perform a workload at

the same relative percentage of their maximal capacity pre and post training. Thus, the stress

placed on the metabolic system should be equal before and after training. This is beneficial because

any significant metabolic adaptation will not simply be the product of a less strenuous workload. In

an experimental model using the same absolute intensity, a group works at the same absolute

workload pre and post training. This makes the absolute demand for energy constant. Thus,

comparing rates of substrate utilization is simplified. This approach does not mimic real life since a

higher intensity of exercise is needed after training to elicit the same metabolic response. However,

comparing absolute rates of substrate utilization can demonstrate mechanisms that cause the

training effects. This review will consider longitudinal studies using both relative and same absolute

intensities. The strengths and weaknesses of each experimental model must be a factor in the data

interpretation.

A variety of research models and methodological approaches have ultimately provided a large body

of literature related to metabolic adaptations to endurance training. Of primary importance are

adaptations in oxidative enzymes and mitochondria.

2. IMPROVED MITOCHONDRIAL RESPIRATION

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Although the effects of endurance training on substrate metabolism have been well described, the

underlying mechanisms responsible for these adaptations have only been partially identified. Most

attention has been focused on the training-induced increase in muscle respiratory capacity. For

many years it was accepted that the metabolic adaptations to endurance training were a function of

improved cardiac function and therefore improved 02 delivery and uptake (Coggan and Williams,

1995). This belief was questioned in 1967 when Holloszy observed a doubling of respiratory

capacity of the mitochondria after a strenuous program of endurance running (Holloszy, 1967). The

twofold increase in mitochondrial oxidative capacity reported was also associated with a doubling of

ATP production and an improved ability to oxidize pyruvate. Accompanying this increase in muscle

respiratory capacity was a sixfold increase in endurance performance. Subsequent studies have

supported the finding that mitochondrial adaptations occur independent of cardiovascular

adaptations (Gollnick et aI., 1972; Morgan et aI., 1971).

The most pronounced mitochondrial adaptation is an increase in the size and number of

mitochondria. (Gollnick et aI., 1972; Hoppler et aI., 1973.) This quantitative increase in the

mitochondria is associated with an increase in most mitochondrial enzymes, increased transport,

and reduced ADP in the cytosol. Before explaining how mitochondrial adaptations aid fat oxidation it

is important to understand the structure and content of the mitochondria. Then after understanding

the changes the mitochondria undergo, the significance of these changes can be examined.

2.1. Mitochondrial Structure and Compartmentalization

All mitochondria are composed of outer and inner phospholipid membranes, an intermembrane

space, and an intemal soluble matrix. Each compartment is associated with specialized functional

capabilities. The outer membrane is the site of protein transporters. The inner membrane contains

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the protein complexes that function in oxidative phosphorylation and electron transport. This inner

membrane is folded into cristae to increase surface area. The soluble matrix compartment inside

the mitochondria contains the enzymes of the Krebs cycle and beta oxidation (Essig, 1996).

2.2 Increased Mitochondrial Size and Number

One major adaptation of the mitochondria is an increase in size and number. The increased size of

individual mitochondria provides a greater surface area exposed to cytosol. Expanded surface area

of each mitochondrial membrane results in more translocation (delivery of metabolites through the

plasma membrane) between the cytosol and mitochondria. The increase in total surface area

means accelerated uptake of metabolites (fatty acids, pyruvate, etc.) by the mitochondria. An

increase in number of mitochondria accomplishes the same end.

Despite numerous studies indicating an increase in mitochondria size and number, minimal

information exists related to the molecular basis for training-induced mitochondria changes. Recent

biological findings add to the knowledge of previous morphological and biochemical analysis of

endurance training adaptations. These stUdies have been successful in describing some of the

processes leading to mitochondrial biogenesis in muscle (Essig, 1996). The mechanisms for

mitochondria structure changes are beyond the scope of this paper. Several excellent reviews

(Essig, 1996; Hake et aI., 1990; Williams, 1990) are available addressing these biogenetic

adaptations.

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2.3 Increase in oxidative enzymes

The increase in mitochondrial volume observed after training is associated with a greater

concentration of mitochondrial enzymes. As noted above, the enzymes which function as mediators

of mitochondrial respiration are located within the matrix of the mitochondria. The increased volume

of mitochondria resulting from endurance training provides a similar response in the mitochondrial

enzymes. The enzymes involved in fatty acid oxidation and the enzymes of the citric acid cycle

increase. A mean increase of 40-50% in the oxidative enzymes elicits improved mitochondrial

efficiency (deVries and Housch, 1994). The mitochondrial composition is variable with some

enzymes increasing 2-fold in concentration while others experience a 35-60% increase in

concentration. Still other enzymes including mitochondrial alpha-glycerophosphate dehydrogenase,

creatine phosphokinase, and adenylate kinase register no statistically significant increase (Spina et

aI., 1992). Since enzyme concentration is proportional to enzyme activity, this research

demonstrates a concentration dependent increase in mitochondrial enzyme activity associated with a

program or endurance training.

Wilmore and Costill reported that two major enzymes in the citric acid cycle, succinate

dehydrogenase (SOH) and citrate synthase (CS), respond to training. Endurance trained individuals

jogging or cycling an hour daily demonstrated a 2.6 fold increase in SOH activity in a longitudinal

study (Wilmore and Costill, 1994). Town and Essig undertook a comprehensive study to document

the timeline for mitochondrial metabolic enzyme increases. The findings indicate that SOH,

cytochrome oxidase (CO), cytochrome reductase (CREO) and CS increase in a coordinate manner

after just two weeks of endurance training. These metabolic enzymes continued to increase in

subsequent training weeks. Essig then consolidated data from four studies (Davies et aI., 1981;

Kirkwood 1986; Mole et al. 1971; and Oscai and Holloszy, 1971) to demonstrate the magnitude of

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the enzymatic response to training. After 10-12 weeks of endurance training the data collected from

the soleus, gastrocnemius, and quadriceps of rat demonstrated an overall increase in 22 key

mitochondrial proteins and pathways for oxidation. While these data must be extrapolated to human

tissue, the results indicate a remarkable adaptation showing an average of twofold increases in over

20 oxidative enzymes. These adaptations are physiologically significant and have been reproduced

in several studies (DeVries and Housh, 1994; Gollnick and Hodgson 1986; Green et. ai, 1991;

Holloszy, 1975 ).

2.4 Effects of Mitochondria Adaptations

There is a strong correlation between improved mitochondrial respiration and the energy substrate

shift associated with endurance training (Moore et al.,1987). However, the biochemical mechanisms

responsible for the energy substrate shift from carbohydrate to fat oxidation are unclear. Improved

mitochondrial content should enhance the ability to oxidize Acetyl-CoA irrespective of the source

(glycolysis vs. beta-oxidation). This begets the question: How does a greater muscle mitochondrial

content lend preference for Acetyl-CoA from beta oxidation instead of glycolytic pathways? Recent

studies have presented some plausible answers.

2.4.1 Decreased cytosolic ADP as a metabolic regulator

One theory to explain the shift in substrate utilization with training is a decreased disturbance of

energetic homeostasis (Coyle et al.,1985; Holloszy, 1967; Holloszy and Coyle, 1984). During

exercise, the rate of ATP hydrolysis increases up to 100-fold in skeletal muscle. To maintain

energetic homeostasis (a balance between ATP and ADP) the body must react quickly to the

depleted reserves from accelerated ATP breakdown. ATP synthesis through the chemical reaction

of oxidative phosphorylation is rapidly needed to match the increased rate of ATP hydrolysis. To

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maintain skeletal muscle function and contractile activity, ATPases located in the cytoplasm break

down ATP and produce ADP and Pi:

ATP~ ADP + Pi + H+

Cytoplasmic ADP is transported into the matrix of the mitochondria via the adenine nucleotide

translocase in exchange for ATP released into the cytoplasm. The free Pi is transported into the

mitochondria via a Pi/H+ symport (Gollnick and Hodgson, 1986). Symort is a method of facilitated

diffusion across the membrane when two types of solute molecules (Pi and H) are transported in the

same direction. To keep the ATPases supplied with required substrate skeletal muscle mitochondria

must convert the ADP and Pi back into ATP. This is accomplished through oxidative phosphylation.

3ADP + 3Pi +NADH +1/202+H+~ 3ATP + NAD+ +H20.

This conversion of ADP and PI to ATP within the mitochondria matrix is driven by the proton

electrochemical gradient. The influx of protons (H+ byproduct from ATP breakdown) from the

concentration gradient drive the enzyme F1 F1 OATPase into the mitochondria. This enzyme

catabolizes ADP and Pi to form ATP (Spriet and Howlitt, 1999).

The speed at which ATP is synthesized is directly related to the speed with which the ADP is

transported into the mitochondria. This is reliant on the concentration of mitochondrial protein. This

conclusion is based on the fact that by having a greater concentration of mitochondrial protein,

(whether as a result of an increase in number or size} there is a greater surface area available for

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translocase. The effect is rapid translocation of ADP into the mitochondria providing the net effect

of a low concentration of ADP in the cytosol (Spriet and Howlitt, 1999).

The reduced quantity of ADP in the cytosol has an impact on the ratio of ATP to ADP in the cytosol.

Before training, translocation is slower and ADP accumulates in the cytosol. After a training

program, the ADP is efficiently transported into the mitochondria because there is more surface area

available for transport. The net result of these adaptations is a smaller displacement of the

ATP/ADP ratio from its rest value (Coggan and Williams, 1995). Since ATP provides the energy for

human movement in the body, this ratio is termed energetic homeostasis. To summarize, when

mitochondrial adenine nucleotide translocation is increased via increases in mitochondria number

and/or size more ADP can be exchanged for ATP. This minimizes cytosolic ADP concentration.

Since the ratio is displaced less post training, energetic homeostasis is more effectively maintained.

An improved ability to maintain homeostasis is a mitochondrial adaptation of a chronic endurance

training program. (Gollnick and Hogsden, 1986).

The importance of maintaining energetic homeostasis is in its ability to slow glycolysis. One theory

espouses that one of the prime regulators of glycolysis is the ATP/ADP ratio. Maintenance of this

ratio retards glycogen degradation. The accumulation of ADP in the cytosol promotes glycogenolysis

at a level where pyruvate production will exceed the need of the citric acid cycle for acetyl units.

Lower cytosolic ADP concentrations will mean a lower pyruvate production. Acetyl CoA is produced

from pyruvate in the presence of oxygen as well as fatty acids derived from beta-oxidation. With a

decreased production of pyruvate, a greater percentage of the available acetyl CoA units will be

derived from beta oxidation. Thus, the acetyl units derived from beta oxidation will compete more

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favorably with those generated from the pyruvate dehydrogenase complex (Coggan and Williams,

1995; Jeukendrup et aI., 1998).

2.4.2 Decreased accumulation of AMP

The maintenance of energetic homeostasis and the attenuated increase in ADP levels in the cytosol

provide an auxiliary effect. The smaller increase in ADP and Pi result in a decreased accumulation

of AMP by adenylate kinase.

2ADP ~ ATP + AMP

Remember that the enzymes of carbohydrate metabolism are regulatory. That is, their actions are

modulated by the relative concentrations of ATP, ADP, AMP and NADH. A decrease in the

accumulation of ADP and AMP, two regulatory enzymes for carbohydrate metabolism, inhibit many

of the enzymes of glycolysis. The overall effect is to decrease the rate of glucose oxidation as fat

oxidation becomes the more important source for ATP production (Horowitz and Klein, 2000).

2.4.3 The possible role of malonyl CoA

Until recently it was assumed that increased fatty acid uptake and oxidation allowed glycogen to be

spared. A possible alternative to this theory is that the increase in fatty acid oxidation is the result of

decreased carbohydrate oxidation, not the cause. Studies suggest that malonyls CoA (the first

intermediate in fatty acid synthesis and potent inhibitor of carnitine acyltransferase I (CAT I) ) may

play an important role in regulating fatty acid oxidation in skeletal muscle (Elayan and Winder, 1991;

Odland et. ai, 1996). CAT I is rate limiting step for long chain fatty acid-CoA entering the

mitochondria. CAT I has been suggested to be an important regulating site of fatty acid oxidation. It

has been hypothesized that a decrease in malonyl CoA during exercise may be important in allowing

entry of more long-chain fatty acids into the mitchondria for beta oxidation (Jeukendrup et aI., 1998).

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During prolonged exercise malonyl CoA concentrations in the muscle decrease (Elayan and Winder,

1991). This decrease parallels carbohydrate availability. CAT I is sensitive to changes in malonyl

CoA concentration. When malonyl-CoA concentration decreases, CAT I is no longer inhibited and

long-chain fatty acids are transported into the mitochondria. This would mean less competition

between acetyl CoA from carbohydrate and the acetyl CoA derived from fat for entry into the citric

acid cycle (Coggan and Williams, 1995). Odland et al.(1996) reported the first measure of malonyl

CoA in humans and reported a statistically unsignificant 20% decline during exercise. While

intriguing, additional experiments will be required to test the validity of this hypothesis (Coggan and

Williams, 1995).

2.5 Correlation of Mitochondrial Adaptations and the Substrate Shift

The metabolic alterations in the mitochondria undoubtedly playa major role in accounting for the

slower rate of glycogenolysis in muscle evident after an endurance training program. The slower rate

of plasma glucose utilization during exercise after training also appears to be a function of the

increase in muscle respiratory capacity (Coggan et aI., 1992). As previously discussed, the precise

biochemical mechanisms accounting for this effect are less clear. It is clear that the enzymes of the

Krebs cycle are activated, and that certain regulators of glycolysis are inhibited. However, these

effects of increased mitochondrial capacity fail to clearly explain the preference for beta-oxidation

and fat metabolism observed with chronic endurance training. While the adaptations to the

mitochondria are well understood, their impact on glycogen sparing and concurrent increases in fat

oxidation is still unclear. Nevertheless, highly significant correlations have been demonstrated

between muscle respiratory capacity and substrate use during exercise (Moore et aI., 1987). After

two weeks, the time course of training induced alterations in substrate utilization during exercise

closely parallels the time course of the increase in mitochondrial enzyme levels (Spina et aI., 1996).

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Therefore, it is clear that the increase in muscle respiratory capacity with its influence on cellular

energetics is one of the important means for the alterations in substrate metabolism associated with

training.

2.5.1 Timecourse for adaptations

Although an abundance of data exists to support the involvement of mitochondrial adaptations to

explain the reduced reliance on glycogen stores and increased fat oxidation, there is still some

debate as to the relative importance of mitochondrial especially during the early phases of a training

program. Green eta I. published a series of three studies that demonstrated a substrate shift before

mitochondrial adaptations were detected. When an increase in mitochondrial enzyme activity was

noted, there was a further increase in fat oxidation. After 5-7 days and 10-12 days of training, no

evidence of an increase in mitochondrial enzymatic markers were noted even though muscle

glycogen utilization and RER during exercise were reduced (Green et ai, 1992; Green et. ai, 1992).

The respiratory exchange ratio, RER, is a numerical value that indicates the body's choice of

substrate. A reduced respiratory exchange ratio indicates more fat and less carbohydrate are being

used as fuel. From these results, Green hypothesized that at least with short-term training,

mechanisms besides mitochondrial adaptation must account for training induced changes in

substrate metabolism during exercise. These findings lead us to examine the hormonal adaptations

to training and the timeline for their impact.

3. 'HORMONAL ADAPTATIONS

3.1 The Nature of Hormones

Hormone is the term for the chemical entity secreted by an endocrine gland. Chemically, hormones

are either steroid, protein, or amino acids (derivatives of protein.) Secretion of hormones occurs

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throughout the body originating in the many locations including the adrenal medulla, anterior

pituitary, adrenal cortex, and pancreas. The nature of hormones is to create action at a target cell.

This action is usually a regulatory function that results in either an acceleration or deceleration of

cellular processes.

Hormone secretion from remote locations provides one mechanism to regulate the substrate

metabolism occurring in active skeletal muscle. There are four major hormones involved in both

glycogenolysis and gluconeogenesis. These include: glucagon, epinephrine, norepinephrine, and

cortisol. These four hormones work to increase the amount of circulating plasma glucose. While

these hormones primarily regulate glucose metabolism, fat metabolism is regulated by some of the

same hormones. Growth hormone, epinephrine, norepinephrine and cortisol regulate fat metabolism

by activating lipase, the enzyme responsible for lipolysis (Wilmore and Costill, 1994).

All of the above hormones experience similar responses to exercise in that all increase. This follows

logic since glucose and fat substrate use increases with exercise to provide ATP for energy. After

training the acute response of each hormone is altered. The catecholamines, insulin, glucagon,

growth hormone, and cortisol all exhibit a unique response to endurance training that has an impact

on the increased fat oxidation associated with endurance training. The hormones' response to

chronic endurance exercise will be reviewed during exercise and at rest.

3.2 Catecholamine Response to Endurance Training

The catecholamines, epinephrine (E) and norepinephrine (NE), are produced in the adrenal medulla.

Also known as adrenaline and noradrenaline, these hormones are released in response to stress.

Although relative amounts vary with physiological conditions, approximately 80% of the secretion is

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epinephrine and 20% norepinephrine (Wilmore and Costill, 1994). Exercise is a form of stress and

elicits their secretion form the autonomic nerve endings and the adrenal medulla. Epinephrine is

secreted from the chromaffin cells of the adrenal medulla whereas norepinephrine is produced in the

adrenal medulla and released from activation of adrenergic nerves. The release of the

catecholamines elicits the stress response throughout the body. This includes an elevation in heart

rate, blood pressure, and stimulation of the sympathetic nervous system (Robergs and Roberts,

1997). The catecholamine impact of the catecholamine response on substrate metabolism is more

complex.

3.2.1 Exercise response of the catecholamines

The acute exercise response of catecholamines is to increase proportional to the intensity of

exercise (Robergs and Roberts, 1997). These hormones work together to increase the release of

glucose and free fatty acids into the bloodstream. E and NE work with glucagon to further increase

glycogenolysis, the catabolism of glycogen. This process occurs within the skeletal muscle and at

the liver. Glucose is released from the liver to increase plasma glucose that becomes readily

available at the muscle. Simultaneously, the release of E and NE contributes to the mobilization and

oxidation of free fatty acids. Cortisol also stimulates lipolysis, the oxidation of fats, before reaching a

plateau value. The catecholamines aid cortisol in activating lipase, which reduces triglycerides to

FFA and glycerol. The magnitude of these responses and their effect on substrate metabolism is

impacted by endurance training.

3.2.2 Training effect on catecholamines

Epinephrine and norepinephrine increase less during exercise after a program of chronic endurance

training (Green et aI., 1991; Hartley et aI., 1972; Koivisto et aI., 1982; Mendenhall et al.,1994).

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These results were conclusive at same absolute intensity and relative intensities in the trained state

compared with the untrained state. Both cross-sectional (Bloom et. ai, 1976) and longitudinal

studies (Hartley et aI., 1972; Winder et ai, 1979) demonstrate the diminished hormonal response to

endurance training. The adaptations of epinephrine and norepinephrine occur very rapidly. Lower

catecholamine levels are visible after just 3 days of endurance training (Green et. ai, 1991). These

rapid changes begin the energy substrate shift augmented by improved mitochondrial content in later

weeks. These effects of training are only evident when the same mode of exercise is compared and

are therefore a unique response to exercise and not merely a function an increase in V02 max

(Coggan and Williams, 1995). At rest, the hormone balance between trained and untrained

individuals is different. DeVries and Housh demonstrated that trained individuals have higher

catecholamine concentrations during the active day than untrained individuals (1994). The

implications of this difference are unclear.

3.2.3 Significance of the training response

Epinephrine

Training reduces the release of catecholamines, and this seems to occur at the same time as an

increase in fat oxidation during submaximal exercise. (Rannollo and Rhodes, 1998). The

significance of the catecholamine response is not clearly defined. Reduced epinephrine levels after

training slows glycogenolysis during exercise. Lower epinephrine response to exercise coupled with

a decrease in insulin secretion, seems likely to contribute to reduced rates of hepatic glucose

production (Coggan et al.; 1990; Mendenhall et al. 1994). Similarly, the combined reduction in

epinephrine and insulin secretion reduces the rate of adipose tissue lipolysis during exercise after

endurance training (Martin et al. 1993). Accompanying a reduced rate of adipose lipolysis is an

increase in intramuscular lipolysis. A greater mass of muscle triglycerides provides a greater

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proportion of total fax oxidized. Mechanisms providing increased lipid source within the muscle will

be discussed later.

Increased intramuscular triglycerol stores do exist and an increase sensitivity and/or responsiveness

of skeletal muscle to lipolysis during exercise accounts for the increase fat oxidation observed post

training (Martin, 1996; Horowitz and Klein, 2000; Rannallo and Rhodes, 1998). An increase in fat

oxidation observed with endurance training may be because of the B-adrenergic (B2) receptor

response to epinephrine in skeletal muscle. The B2 receptors trigger oxidation of intramuscular

triglycerides. Studies show increased B2 receptor stimulation in trained individuals (Cleroux et. aI.,

1989). This increased stimulation is credited to increased sensitivity or responsiveness because

endurance training in humans does not increase skeletal muscle B-adrenergic receptor density.

Norepinephrine

Unlike epinephrine that is released from the adrenal medulla, most norepinephrine enters the body

as "spillover" from sympathetic nerves (Esler et al.,1984). Plasma norepinephrine levels indicate the

level of activation of the sympathetic nervous system. The release of norepinephrine and its uptake

occur simultaneously as norepinephrine is releases at various tissue sites. This procedure makes

assessment of whole body sympathetic responses difficult to attain. Each limb may be activated at

different times and with different magnitudes. Still, plasma norepinephrine levels have a strong

correlation with more direct measures of sympathetic nervous system activity

(Wallin et aI., 1981). Therefore, the lowered plasma norepinephrine levels post training indicate an

overall decrease in sympathetic nervous system stimulation.

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The impact of norepinephrine of the metabolic shift is largely indirect. Norepinephrine has little

impact on the adrenergic receptors of human muscle. Therefore, norepinephrine levels can not

directly impact muscle glycogen sparing or muscle triglyceride metabolism. Instead, reduced levels

of norepinephrine during exercise are thought to have an effect on substrate metabolism by altering

the concentrations of other hormones like epinephrine and insulin. Release of norepinephrine at

peripheral tissue can reduce FFA and glucose mobilization form adipose and liver tissue. A reduced

sympathetic response and reduced "spillover" of norepinephrine could reduce mobilization of these

fuels after training (Esler et aI., 1984). To confirm these hypotheses, direct measurement of tissue

during exercise pre and post training would need to be performed.

3.2.4 Conflicting reports

While a program of chronic endurance training has shown a relatively consistent catecholamine

response, some studies have reported that plasma epinephrine levels are higher in trained

endurance athletes than in untrained men during prolonged exercise (Kjaer and Galbo, 1988). It has

been demonstrated that the level of epinephrine was two-fold higher in trained athletes during

exercise compared to non-athletes (Kjaer and Galbo, 1988). These apparent inconsistencies have

been attributed to hypertrophy of the adrenal medulla. Increased adrenal medullary mass is thought

to increase epinephrine secretion in response to stress. Interestingly, hypertrophy of the adrenal

medulla in rats from swim training actually reduces the epinephrine response during exercise

(Stallkenecht et aI., 1990).

Cross sectional studies indicating higher epinephrine levels in trained individuals may be due to a

selection phenomenon. Those individuals with greater adrenal medullary responsiveness may be

more likely to succeed and therefore to continue participation in sports. Previous studies on

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physiological "toughness" support the selection phenomenon. Individuals with greater

sympathoadrenal responsiveness are better able to cope with acute stress (e.q. very cold

environment) and this has been associated with improved "toughness" and athletic performance.

Longitudinal studies would be required to determine whether endurance training in humans at elite

training levels does increase epinephrine secretion and if so, if this effect is observed during

exercise.

3.3 Insulin and Glucagon Responses to Endurance Training

Other hormones influence the substrate shift that promotes fat oxidation directly or in combination

with the catecholamines. Two of these mediating hormones, insulin and glucagon, are secreted

from the pancreas. Glucagon and insulin work together to control blood-glucose levels. Insulin is

released when plasma glucose levels are high and facilitates glucose transport into the cells. Insulin

also promotes glycogenesis (glycogen synthesis) and inhibits gluconeogenesis (conversion of fat to

glucose) (Wilmore and Costill, 1994). The main function of insulin is to reduce plasma glucose and

performs auxiliary duties promoting cellular uptake of amino acids and enhancing protein and fat

synthesis. Glucagon is secreted during hypoglycemic conditions and opposes insulin by promoting

glycoenolysis and increasing gluconeogenesis. These processes increase plasma glucose, which

insulin works to reduce.

3.3.1 Exercise responses of insulin and glucagon

During submaximal exercise insulin levels usually decline following 30 minutes of exercise. Insulin

decreases but plasma glucose levels remain constant. The number and availability of insulin

receptors increases during exercise. Therefore, the amount of insulin needed to maintain plasma

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glucose levels decreases. Concurrently, plasma glucagon rises gradually through exercise.

Glucose is more readily available to active cells.

3.3.2 Insulin training response

With training, insulin levels tend to decrease less during exercise in the trained state (Coggan et aI.,

1990; Hartley et aI., 1972; Mendenhall et aI., 1992; Winder et. al.,1979). Basal insulin

concentrations are often lower in trained subjects versus untrained subjects. However, the insulin

response to exercise is greater in trained individuals. The significance of this adaptation is a

decreased stimulus to use blood glucose. When exercise intensity exceeds 50% of V02 max the

insulin concentration in peripheral plasma decreases in direct proportion to the increase in workload

(deVries and Housh, 1994). Similar to the catecholamines, the significance of this training effect has

not been firmly established.

3.3.3 Significance of the training response

The relatively higher insulin in the trained state may inhibit hepatic glucose production and lipolysis.

In turn, this may contribute to the slower rates of glucose and FFA release during exercise and

subsequent oxidation of intramuscular triglycerides. The timecourse for this adaptation supports this

theory and necessitates the role of catecholamines in the process. Insulin levels show the greatest

divergence from pre training concentrations during the later stages of exercise. The inhibition of

hepatic glucose production and lipolysis is observed throughout exercise. It can be concluded that

the training effect of insulin is an important mediator for glucose and adipose tissue lipolysis after

thirty minutes of exercise. The body relies on the catecholamines as an immediate stress response

to initiate this inhibition. Further support for this theory is the timecourse for insulin adaptations.

Greater insulin concentrations during exercise are evident after only ten days of training and glucose

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production began a decline concurrently (Mendenhall et aL, 1994). Hepatic glucose production

continues to decline through a twelve-week endurance training program (Coggan and Williams,

1995). Greater suppression of glucose production and lipolysis is likely influenced by insulin

concentrations and other hormones.

Concurrent with a smaller decrease in insulin secretion during exercise is a greater rate of insulin

stimulated glucose transport into the active skeletal muscle. Seemingly, this training adaptation

would offset the inhibition of glucose production and adipose lipolysis. While appearing paradoxical,

training actually reduces the uptake of plasma glucose during exercise. It has been estimated that in

humans about 85% of the increase in glucose utilization during exercise results from mediators other

than insulin (Coggan and Williams, 1995). The relatively higher insulin concentration associated with

training is more important for its inhibitory effects of glucose production and adipose tissue lipolysis

that for its influence on glucose utilization. This explains the apparent paradox of a lessened

decrease in insulin levels and the glycogen sparing associated with endurance training.

3.3.4 Glucagon training response

Glucagon exhibits the opposite training effect of insulin. Glucagon levels are reduced during exercise

after training (Coggan et aL, 1990; Mendenhall et aL, 1994; Winder et aL, 1979). The effects of

exercise training on glucagon follow a similar timecourse to the adaptations of insulin. Glucagon

plays an auxiliary role in the training-induced glucose output during exercise.

3.4 Cortisol Response to Endurance Training

Cortisol, also known as hydrocortisone, is responsible for almost 95% of all glucocorticoid activity in

the body (Robergs and Roberts, 1997). The glucocorticoids are some of the thirty steroid hormones

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secreted by the adrenal cortex. Stimulation of the adrenal cortex by adrenocorticotropin (ACTH)

causes the release of cortisol into the blood stream. Cortisol has whole body effects as an immune

system depressant and anti-inflammatory agent. Metabolically, cortisol stimulates gluconeogenesis,

increases free fatty acid mobilization from adipose tissue and decreases glucose utilization and

stimulates protein catabolism (Wilmore and Costill, 1994).

3.4.1 Exercise response of cortisol

ACTH levels are elevated during physical activity and mediate an exercise-induced increase in

cortisol. Studies demonstrate that the degree of stress, defined as intensity during exercise

determines the exercise-induced increase in cortisol. Cortisol levels increase significantly with work

loads above 50% V02 max. (DeVries and Housh, 1994.) During light to moderate work plasma

glucocorticoid levels remain fairly constant and the growth hormonal level rose significantly with

more difficult work loads. As exercise intensity increases, a dichotomy exists between the body's

ability to remove cortisol from circulation and the secretion from the adrenal cortex (Robergs and

Roberts, 1997).

3.4.2 Training response of cortisol

Cortisol increases less during submaximal exercise after a program of chronic endurance training in

both absolute and relative intensity studies (Robergs and Roberts, 1997). The significance of this

training effect is most evident in the decreased gluconeogenesis at the liver. A lessened increase in

cortisol post training blunts the effects of cortisol at adipose tissue sites as well. Cortisol works in

concert with the catecholamines and growth hormone which also impact fatty acid mobilization and

glucose production. Cortisol levels peak and then return to near normal levels during prolonged

exercise. Then, growth hormone and the catecholamines take over cortisol's role.

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3.5 Growth Hormone Response to Endurance Training

Growth hormone is secreted from the anterior lobe of the pituitary and targets all cells in the body

including active skeletal muscle. The factors that combine to regulate growth hormone are growth

hormone releasing hormone (GHRH) and somatostatin. Throughout the body growth hormone

mediates the maturation and development of tissue, increases protein synthesis and increases the

mobilization of fats. Additionally, growth hormone increases the use of fat and decreases the rate of

carbohydrate use. Growth hormone increases fat mobilization by activating hormone sensitive

lipase.

3.5.1 The exercise response of the growth hormone

Exercise results in an increase in growth hormone concentration (Wilmore and Costill, 1994).

Growth hormone registers a small increase in concentration during the first 40 minutes of

submaximal exercise. Between forty and sixty minutes, concentrations of growth hormone

experience a 100% increase. After 80 minutes of exercise growth hormone levels are 300% of

resting plasma growth hormone levels (Wilmore and Costill 1997). This 300% increase parallels the

cortisol decrease after 45 minutes of exercise. During prolonged work, the increase in growth

hormone begins to recede toward resting values but still remains elevated for some time after

exercise (deVries and Housh, 1994).

3.5.2 Training response of growth hormone

Growth hormone increases less in trained individuals and maintains greater stability throughout

exercise. Also, growth hormone declines faster post-exercise in a fit person (Wilmore and Costill

1994). The normal exercise response of growth hormone elicits increased glucuconeogenesis, FFA

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mobilization and decreases glucose uptake. These responses are similar before and after training

(Robergs and Roberts, 1997). This effect mirrors the effect of cortisol and both serve to inhibit fatty

acid uptake from adipose tissue and hepatic glucose production. The significance of this response is

the collaborative role of growth hormone and with the training responses of the catecholamines and

cortisol. The increase in blood concentrations of FFAs and amino acids that accompanies increases

in GH and cortisol provides substrates for gluconeogenesis and lipid fuel for skeletal muscle energy

metabolism.

3.6 The Net Effect of Hormones in the substrate shift

While each hormone has specific target cells and responses, the actions of hormones are

interdependent. There are many examples of this interdependent relationship. Insulin and glucagon

work in opposition to effect plasma glucose levels. Cortisol begins lipolysis and the catecholamines

and growth hormone continue the role when cortisol levels taper. The interdependent nature of the

hormones make the net effect of exercise training a very important consideration. All of the

hormones work to achieve some common effects with the exception of insulin. Insulin is active only

in transporting glucose into the cell. However, the available glucose is decreased and mediators

besides glucose are responsible for at least 85% of glucose uptake.

With insulin's impact on metabolism mitigated, the catecholamines, cortisol, and growth hormone

cooperate to decrease adipose tissue lipolysis and glucose production and uptake. Decreased

accumulation of these hormones during exercise facilitates this net effect. Interestingly, this

decrease in adipose tissue lipolysis occurs concurrent with increases in fat oxidation. This apparent

paradox is explained by a change in the body's sources for increased fat oxidation.

4. SOURCES OF INCREASED FAT FOR OXIDATION

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Several sources of lipid fuel exist within the body. These include: adipose tissue, muscle adipocytes,

muscle fiber triglycerides, lipoproteins, and plasma free fatty acids. Of these sources, two are

primarily used during submaximal exercise. These sources are fatty acid uptake from adipose tissue

and muscle (Rannolo and Rhodes, 1998). However, a decrease in fatty acid uptake from adipose

sites is observed in trained individuals (Martin, 1996).

4.1 Intramuscular Triglycerides Fuel the Substrate Shift

It has been hypothesized that a decrease in FFA uptake may be accompanied by enhanced skeletal

muscle uptake of FFA. A longitudinal study was undertaken by Martin et. al. to determine the rate of

FFA uptake and oxidation before and after a twelve-week strenuous endurance program. Data was

obtained from plasma samples drawn during constant-rate intravenous infusion the stable isotope

tracer palmitate (1-13C) (Havel et al. 1963). Results after absolute trials at 64% of the pretraining

V02 max cycling indicted a 20-32% decrease in plasma concentrations of palmitate, total FFA, and

glycerol (Martin et al., 1996). These results are confirmed by other studies (Coggan and Williams

1995; Horowitz and Klein, 2000). These results also indicated a strong correlation between plasma

FFA concentrations and FFA oxidation and demonstrated no enhanced uptake of FFA after training

(Martin 1997).

4.2 Increased Sensitivity to Plasma FFA Fuels the Substrate Shift

Results from Turcotte et al. (1992) did find enhanced uptake of FFA after training. Turcotte et al.

found increases in the maximal capacity for FFA transport into skeletal muscle by increasing the

concentration of fatty acid binding proteins. The seemingly opposite results reported by Martin and

Turcotte may not necessarily be in conflict, but may be due to a difference in exercise modes.

Martin and previous studies indicating no increase in FFA uptake and oxidation adopted a cycle

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ergometer protocol for exercise testing. Turcotte et al. measured plasma concentrations after

endurance training during the third hour of single-leg knee-extension exercise. The lipolytic hormone

concentrations were unaffected during the 3rd-hour knee single leg knee extensions enabling levels

of FFA mobilization to be maintained in the Turcotte study. However, in whole body exercise with

large muscle groups the training effect of hormones is apparent and represses adipose and FFA

uptake and use. (Coggan and Wiliams, 1995).

4.3 Evidence of increased intramuscular triglyceride utilization

As it has been demonstrated, plasma FFA can not account for increased fuel for fat oxidation during

submaximal exercise with large muscle groups. The primary fuel source for increased fat oxidation

associated with endurance training becomes muscle triglycerides (Horowitz and Klein, 2000; Martin

et al. 1993). This paper has established that the mechanisms for this shift are only partially

understood. Additionally, no definitive conclusion has been reached to determine whether the

increase in muscle triglyceride use favors fat from muscle fiber sites or adipocytes interspersed

within the skeletal muscle (Rannalo and Rhodes, 1998). Hurley et al. demonstrated the ability of

muscle lipolysis to supply the necessary energy after a program of chronic endurance training. After

training a doubling of muscle triglyceride use was evidenced (1996). To supply the necessary

energy for prolonged exercise, the storage of muscle triglycerides increases.

5. CONCLUSION

Much progress has been made regarding the effects of endurance training on substrate metabolism

during exercise. It is now understood that endurance trained humans experience an increased

reliance on fatty acids for energy during exercise at any given intensity. This increased reliance on

fat oxidation is paralleled by a decreased role of muscle glycogen and plasma glucose during

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exercise. These training adaptations playa major role in the performance improvements

demonstrated with endurance training. The energy substrate shift allows glycogen sparing to occur

and time until fatigue is prolonged. Similarly, the reliance on increased fat for energy provides a

greater amount of energy per unit of mass.

The active skeletal muscle is the site of mitochondrial adaptations, hormonal mediation, and

increased lipolysis that help mediate these effects. It is evident that these metabolic adaptations to

training are largely modulated by adaptations in the mitochondria. Increased size, number, and

enzymatic activity aid the substrate shift. A complete understanding of the mechanisms causing the

training effects at the mitochondria has not been achieved. Hormonal adaptations impacting

sympathetic nervous system activity, liver, and adipose tissue uptake mediate the availability of

substrates for the active skeletal muscle. A net effect of the hormonal adaptations is a reduced

release of fatty acids from adipose tissue and reduced plasma fatty acid concentrations. The

importance of individual hormone adaptations is difficult to quantify. The specific tissue source

providing substrate for increased fat oxidation appears to be muscle triglycerides. An increased

storage and utilization of muscle triglycerides supports this hypothesis but again, additional study is

needed to understand the exact role of muscle triglycerides in the energy substrate shift.

It is clear that fat is increasingly oxidized in humans after endurance training. Adaptations of the

mitchondria, hormonal response, and fuel sources all playa role in this increased fat oxidation. Still,

much remains to be discovered regarding the effects of endurance training on substrate metabolism

within skeletal muscle.

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References 1. Armstrong, D.T., R Steele, N. Altszuler, A. Dunn, J.S. Bishop, and RC. DeBodo. Regulation of plasma free fatty acid turnover. Am. J. Physio/. 201:9-15,1961.

2. Bloom, S.R, RH. Johnson, D.M. Park, M.J. Rennie, and W.R Sulaiman. Differences in the metabolic and hormonal responses to exercise beteen racing cyclists and untrained individuals. J. Physio/. 258:1-18, 1976.

3. Cleroux, J. P. Van Nguyen, AW. Taylor, and F.H.H. Leenen. Effects of B1-vs. B1+B2- blockade on exercise endurance and muscle metabolism in humans. J Appl. Physiol 66:548-554, 1989.

4. Coggan, AR, W. M. Kohrt, R J. Spina, D. M. Bier, and J. O. Holloszy. Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men. J. Appl Physio/. 68:990-996, 1990.

5. Coggan, Ar. and B.D. Williams. Metabolic Adaptations to Endurance Training: Substrate Metabolism During Exercise. Hargreaves, M. ed. Exercise Metabolism. Champaign, IL: Human Kinetics:177-210, 1995.

6. Coyle, E.F., W.H. Martin, SA Bloomfield, O.H. Lowry, and J.O. Holloszy. Effects of detraining on responses to submaximal exercise. J. Appl. Physiol. 59:853-859,1985.

7. Davies, K.JA, O. Packer, and G.A, Brooks. Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training. Arch. Biochem. Biophys. 209:539-554, 1981.

8. DeVries, H.A. and T.J. Housh. Physiology of exercise: for physical education, athletics, and exercise science. 5th

ed. Dubuque, IA: Brown and Benchmark: 177-184, 1994.

9. Elayan, I.M. and WW. Winder. Effect of glucose infusion on muscle malonyl-CoA during exercise. J. Appl. Physiol. 70:1495-1499, 1991.

10. Esler, M. G. Jennings, P. Korner, P. Blombery, N. Sacharias, and P. Leonard. Measurement of total and organspecific norepinephrine kinetics in humans. Am. J. Physiol. 247 (Endocriol. Metab. 10)E21-E28, 1984.

11. Essig, DA Contractile Activity-Induced Mitochondrial Biogenesis in Skeletal Muscle. In: Exercise and Sport Science Reviews. Holloszy, J.O. Ed. 24:289-319, 1996.

12. Gollnick, P.D. R B. Armstrong, CW. Saubert, K. Piehl, and B. Saltin. Enzyme activity and fiber composition in skeletal muscle of untrained and trained men. J. Appl. Physiol. 33:312-319, 1972.

13. Gollnick, P.D. and D.R Hodgson. Enzymatic Adaptation and its Significance for Metabolic Response to Exercise. In: Biochemistry of Exercise VI. Saltin, B. Ed. Champaign,lL:Human Kinetics:191-200, 1986.

14. Gollnick, p.o. and DW King. Effect of exercise and training on mitochondria of rat skeletal muscle. Am. J. Physiol. 216:1502-1509,1969.

15. Green, H.J., M.E. Ball Burnett, D. Smith, J. Livesey, and BW. Farrance. Early muscular and metabolic adaptation to prolonged exercise training in humans. J. Appl. Physiol. 70:2032-2038, 1991.

16. Green, H.J., R Heylar, M. Ball-Burnett, N. Kowalchuk, S. Symon, and B. Farrance. Metabolic adaptations to training precede changes in muscle respiratory capacity. J. Appl. Physiol. 72:484-491, 1992.

17. Hake, L.E., AA Alcivar, and N. B. Hecht. Changes in mRNA length accompany translational regulation of the somatic and testis specifiic cytochrome c genes during spermatogeneSiS in the mouse. Development 110:249-257, 1990.

18. Hargreaves, M., B. Kiens, and E.A Richter. Effect of increased plasma free fatty acid concentrations on muscle metabolism in exerCising men. J. Appl. Physio/. 70:194-201,1991.

28

-

19. Hartley, L.H., J.w. Mason, RP. Hogan, L.G. Jones, T.A. Kotchen, E.H. Mougey, F.E. Wherry, L.L. Pennington, and P.T. Ricketts. Multiple hormonal responses to prolonged exercise in relation to physical training. J. Appl. Physio/. 33:607-610, 1972.

20. Havel, RJ., A Naimark, and C.F. Borchgrevink. Turnover rate and oxidation of free fatty acids of blood plasma in man during continuous infusion of 1-C14 palmitate. J. Clin. Invest. 42:1054-1063, 1963.

21. Henriksson, J. Training-induced adaptations of skeletal muscle and metabolism during submaximal exercise. J. Physio/. (Lond.) 270:661-665, 1977.

22. Holloszy, J.O. Adaptation of skeletal muscle to endurance exercise. Med. Sci. Sports. 7(3): 155-164, 1975.

23. Holloszy, J.O. Biochemical adaptations in muscle. Effects of exercise on miotchondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J. BioI. Chem. 242:2278-2282, 1967.

24.Holloszy, J.O. Biochemical adaptations to exercise: aerobic metabolism. In: Wilmore J, ed. Exercise and sport sciences review. New York: Academic Press:45-71, 1973.

25. Holioszy,J.O., and E.F. Coyle. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J. Appl. Physio/. 56:831-838,1984.

26. Hoppler, H. P. Luthi, H. Claassen, E.R Weibel, and H. Howald. The ultrastructure of normal human skeletal muscle. A morphometric analysis of untrained men, women, and well-trained orienteers. Pflugers Arch. 344: 217-232, 1973.

27. Horowitz, J.F., and S. Klein. Lipid metabolism during endurance exercise. Am. J. Clin. Nutr.72(suppl):558S-63S, 2000.

28. Hurley, B.F.,P.M. Nemeth, W.H. Martin, III, J.M. Hagberg, G. P. Dalsky, and J.O. Holloszy. Muscle triglyceride utilization during exercise: effect of training. J. Appl. Physio/. 60:562-567, 1986.

29. Jeukendrup, AE., W.H.M. Saris, and AJ.M. Wagenmakers. Fat metabolism during exercise: a review. Part I; Fatty acid mobilization and muscle metabolism. Int. J. Sports Med. 19:231-244, 1998.

30. Jeukendrup, AE., W.H.M. Saris, and AJ.M. Wagenmakers. Fat metabolism during exercise: a review. Part II; Regulation of metabolism and the effects of training. Int. J. Sports Med. 19:293-302, 1998.

31. Jansson, E., and L. Kaijser. Substrate utilization and enzymes in skeletal muscle of extremely endurance-trained men. J. Appl. Physio/. 662:999-1005, 1987.

32. Kjaer, M. and H. Galbo. Effect of physical training on the capacity to secrete epinephrine. J. Appl. Physiol.64:11-16,1988.

33. Koivisto, V., R Hendler, E. Nadel and P. Felig. Influence of physical training on the fuel-hormone response to prolonged low intensity exercise. Metabolism 31: 192-197, 1982.

34. Martin, W.H. , G.P. Dalsky, B.F. Hurley, D.E. Matthews, D.M. Bier, J.M Hagberg, M.A. Rogers, D.S. King, and J.O.Holioszy. Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise. Am. J. Physiol (265 (Endocrinol. Metab. 28):E708-E714, 1993.

35. Martin, W. H. III. Effects of Acute and Chronic Exercise on Fat Metabolism. Exercise and Sport Science Reviews. 24:203-228, 1996.

29

-

.-

36. Mendenhall, L.A, S.C. Swanson, D.L. Habash, and AR Coggan. Ten days of exercise training reduces glucose production and utlization during moderate-intensity exercise. Amer. J. Physiol. 226 (Endocrinol. Metab. 29):E136-E143,1994.

37. Mole, PA, L.B. Oscai, and J.O. Holloszy. Adaptation of muscle to exercise. Increase in levels of palmityl CoA synthetase, carnitine palmityltransferase, and palmityl CoA dehydrogenase, and the capacity to oxidize fatty acids. J. Clin. Invest. 50:2323-2330, 1971.

38. Moore, RL, E.M. Thacker, GA Kelley, T.I. Musch, and L.I. Sinoway. Effect of training.detraining on submaximal exercise responses in humans. J. Appl. Physiol. 63:1719-1724, 1987.

39. Morgan, T.E.; FA Short, and L.A Cobb. Effect of long-term exercise on human muscle mitochondria. In: Pernow, B., and B. Saltin, Eds. Muscle metabolism during exercise. New York:Plenum:87-95, 1971.

40. Odland, L.M., G.F.Heigenhause, G.D Lopaschuk, and L.L. Spriet. Human skeletal muscle malonyl-CoA at rest and during prolonged submaximal exercise. Am. J. Physiol. 20:E541-544, 1996.

41. Oscai, L.B. and J.O. Holloszy. Biochemical adaptations in muscle II. Response of mitochondrial adenosine triphosphatase, creatine phosphokinase, and adenyl ate kinase activities in skeletal muscle to exercise. J. Bioi. Chem. 246: 6968-6972, 1971.

42. Rannalo, RE. and E.C. Rhodes. Lipid metabolism during exercise. Sports Med. 26 JuI:29-42, 1998.

43. Robergs, RA and S.O. Roberts. Exercise physiology: exercise, performance, and clinical applications. St. Louis MO: Mosby: 354-375, 1997.

44. Spina, RJ, M.M. Chi, M.G. Hopkins, P.M. Nemeth, O.H. Lowry, and J.O. Holloszy. Mitochondrial enzymes increase in muscle in response to 7-10 days of cycle exercise. J. Appl. Physiol. 80:2250-2254, 1996 .

45. Spina, RJ., T Ogawa, A.R Coggan, J.O. Holloszy, and AA Eshani. Exercise training improves left ventricular contractile response to B-adrenergic agonist. J. ApplPhysiol. 72:307-311, 1992.

46. Spriet, L. L., R A Howlett. Metabolic Control of Energy Production During Physical Activity. In: Lamb,D.R and R Murray Ed. Perspectives in Ex. Sci. and Sports Medicine. V.12 The Metabolic Basis of Performance in Exercise and Sport. Carmel, IN, 1999: 1-45.

47. Stallknecht, B. M. Kjaer,K.J Mikines, L. Maroun, T.Ploug, T. Ohkuwa, J. Vinten J. and H. Galbo. Diminished epinephrine response to hypoglycemia despite enlarged adrenal medulla in trained rats. Am. J. Physio/. 28:R998-R1003,1990.

48. Turcotte, L.P., E. A Richter, and B. Kiens. Increased plasma FFA uptake and oxidation during exercise in trained vs. untrained humans. Am. J. Physio/262(Endocrinol Metab. 25):E791-E799, 1992.

49. Wallin, G.G., G. Sundlof G.M. Eriksson, P. Dminiak, H. Grobecker, and L.E. Linblad. Plasma noradrenaline correlates to sympathetiC muscle nerve activity in normotensive man. Acta Physio/. Scand. 111 :69-73, 1981.

50. Williams, RS. Genetic mechanisms that determine oxidative capacity of striated muscles. Circulation. 82:319-331, 1990.

51. Wilmore, J.H. and D.L. Costill. Physiology of sport and exercise. 2nd ed. Champaign, IL: Human Kinetics; 1994.

52. Winder, W. W., RC. Hickson, and J.M. Hagbergl. Training-induced changes in hormonal and metabolic responses to submaximal exercise. J. Appl. Physio/. 46:766-771,1979.

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