Reducing Body Fat with Altitude Hypoxia Training in Swimmers: Role of Blood
Perfusion to Skeletal Muscles
Michael Chia1, Chin-An Liao2, Chih-Yang Huang3, 4, Wen-Chih Lee5, Chien-Wen Hou2,
Szu-Hsien Yu 2, M. Brennan Harris 6, Tung-Shiung Hsu 2, Shin-Da Lee7, 8, *, and
Chia-Hua Kuo2, 8, *
1National Institute of Education, Nanyang Technology University, Singapore
2Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei 11153
3Institute of Medical Science, China Medical University, Taichung 40402
4Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354
5Committee for General Education, Shih Hsin University, Taipei 11604
6Department
of Kinesiology & Health Sciences, The College of William & Mary,
Williamsburg, VA, USA
7Department of Physical Therapy, Graduate Institute of Rehabilitation Science,
Taichung 40402 and 8Department of Healthcare Administration, Asia University,
Taichung 41354 Taiwan, Republic of China
Abstract
Swimmers tend to have greater body fat than athletes from other sports. The
purpose of the study was to examine changes in body composition after altitude
hypoxia exposure and the role of blood distribution to the skeletal muscle in
swimmers. With a constant training volume of 12.3 km/day, young
male swimmers (n = 10, 14.8 ± 0.5 years) moved from sea-level to a higher altitude of
2,300 meters. Body composition was measured before and after translocation to
altitude using dual-energy X-ray absorptiometry along with 8 control male subjects
who resided at sea level for the same period of time. To determine
the effects of hypoxia on muscle blood perfusion, total hemoglobin concentration
(THC) was traced by near-infrared spectroscopy in the triceps and quadriceps
muscles under glucose-ingested and insulinsecreted conditions during hypoxia
exposure (16% O2) after training. While no change in body composition
was found in the control group, subjects who trained at altitude had unequivocally
decreased fat mass (-1.7 ± 0.3 kg, -11.4%) with increased lean mass (+0.8 ± 0.2 kg,
+1.5%). Arterial oxygen saturation significantly decreased with increased plasma
lactate during hypoxia recovery mimicking 2,300 meters at altitude (~93% versus
~97%). Intriguingly, hypoxia resulted in elevated muscle THC, and sympathetic
nervous activities occurred in parallel with greater-percent oxygen saturation in both
muscle groups. In conclusion, the present study provides evidence that increased
blood distribution to the skeletal muscle under postprandial condition may
contribute to the reciprocally increased muscle mass and decreased
body mass after a 3 -week altitude exposure in swimmers.
Key Words: nutrient partitioning effect, adolescence, NIRS, oxygenation, body fat
Introduction
Competitive swimmers normally carry out a
training volume of several kilometers per day in training,
e x p e n d i n g m a s s i v e a m o u n t s o f c a l o r i e s . H o w e v e r,
their average body fat levels are not lower than other
types of athlete and active non -athletes (7, 12). Swimmers
consuming excessive calories, thereby causing
a positive energy balance, which leads to greater fat
accumulation has been excluded as some well -controlled
studies comparing that compare body composition
a c ro s s s p o r t s d i s c i p l i n e s h a ve s h o w n ( 1 2 ,
18). Still, it is essential to understand the regulatory
mechanism of body composition so as to develop
effective training programs for swimmers to maintain
an optimal body fat composition as a buoyancy aid
w i t h o u t a n y c o m p r o m i s e t o m u s c l e m a s s .
In animal studies, the effects of prolonged systemic
hypoxia exposure on reducing body fat mass (6)
and increasing muscle mass (10) has been established.
Since ambient oxygen for fatty acid oxidation is less
available under hypoxia, fat oxidation would not be
the best explanation for the body fat-reducing effect
of prolonged hypoxia exposure. Here, we considered
that greater distribution of circulatory insulin to the
skeletal muscle could directly alter the deposition of
fuel storage (3), and thus can influence body composition.
Insulin is the main anabolic hormone which
stimulates fuel storage and syntheses of glycogen,
triglyceride and protein in the skeletal muscle and
adipose tissues (29). Therefore, preferential distribution
in circulatory insulin perfusion among tissues
would be expected to alter body composition. This is
evidenced by the fact that withdrawal of insulin in
animals for only 7 days can lead to marked reductions
in fat mass and fat-cell diameter at all depots (13).
Such conditions of shifting insulin delivery can presumably
be maneuvered by increasing blood distribution
t o w a r d s t h e s ke l e t a l m u s c l e . T h e r o l e o f
skeletal muscles in the regulation of fat mass is
demonstrated by interventions that stimulate muscle
growth, which causes substantial reductions in body
fat mass (1).
Due to limitations in assessments of body composition,
reliable data are sparse in proving the beneficial
effects of altitude hypoxia on body composition
in humans. We hypothesize that: [1] a 3 -week altitude
exposure at 2,300 meters can increase lean mass and
decrease fat mass in trained swimmers; [2] hypoxia
can enhance blood distribution towards exercised
skeletal muscles under postprandial insulin -stimulated
c o n d i t i o n s . To t e s t t h e f i r s t h y p o t h e s i s , 1 0 a d o l e s c e n t
male swimmers moved from sea l evel to higher altitude
for a 3-week stay after baseline measurement of body
composition, using dual-energy X-ray absorptiometry
(DXA) as an instrument for body composition measurements.
T o
t e s t
t h e
s e c o n d
h y p o t h e s i s ,
b l o o d
hemoglobin distribution, mirrori ng blood distribution
to skeletal muscles was traced, using near infrared
spectroscopy (NIRS) under glucose -ingested hyperinsulinemic
c o n d i t i o n s d u r i n g r e c o v e r y f r o m t r a i n i n g
under a simulated altitude hypoxia condition.
Materials and Methods
Subjects and Design
The present study contained two separate experiments.
Fo r t h e f irst exp e r im e n t , t h e effe ct s o f a
3-week altitude training on body composition were
determined by DXA in 10 male swimmers (age:
14.9 ± 0.4 years, BMI: 20.8 ± 0.4 kg /m2) who regularly
accomplished a total training distance of 12.3 km per
day with the same volitional training effort at sea
level; all subjects were motivated to complete their
daily swimming volume in the shortest possible time.
After baseline measurements, all subjects move d from
sea level (Singapore) to altitude (2,300 m, Kunming,
Yun nan , P RC ) for 3 we e ks . An add it io na l 8 m a le co nt ro l
subjects (age: 13.0 ± 1.6 years, BMI: 20.5 ± 1.2
kg /m2) residing at sea level were recruited to monitor
possible time-to-time variations of DXA measurements
on body composition. For the second experiment,
effects of hypoxia (at 16% oxygen) on blood
distribution to the skeletal muscle were assessed under
glucose-ingested condition (i.e. insulin-stimulated
condition) after training at sea level. Skeletal muscle
blood distributions were measured using NIRS to
detect changes in hemoglobin concentrations under
hypoxic (16% oxygen) and normoxic conditions for
90 min after oral glucose ingestion. The institutional
r e v i e w b o a r d a p p r o v e d t h e s t u d y, a n d w r i t t e n i n f o r m e d
parental consent and subject assent were obtained
prior to any data collection.
Body Composition
Muscle and fat mass were determined by DXA
before and after the 3-week altitude exposure (within
3 days upon returning to sea level). DXA is an accepted
method used by the European Working Group
on Sarcopenia in Older People for research and for
clinical use to distinguish fat and muscle tissues (9).
The whole-body DXA unit (Hologic QDR Series,
D i s c o v e r y W, H o l o g i c I n c . , B e d f o r d , M A , U S A ) w a s
used. It was equipped with the patented Hologic
continuous calibration system and was operated by a
trained radiation technician who performed all the
scans. The DXA machine was calibrated every
morning during the test days using a standard with a
reproducibility coefficient of r = 0.90. All data were
generated from the Hologic computer software (Version 9.8). DXA is based on the
principle of differential attenuation of two different X -ray energies
(h igh: 1 40 kVp ; low: 10 0 kVp ). Part icipant s were requ ired
to remove all metallic elements from the body
and lay supine on the table, arms by the side with the
palms pronated. The hips were internally rotated
until both the great toes touched. The ankles were
secured with velcro straps. The participants were
advised to lie as still as possible during the scanning
process which took about 7 min. Each participant
received 0.02 mrem of radiation dose, equivalent to
about 5% of the dose of a usual chest X -ray.
NIRS Measurement
NIRS is now a well-accepted method to estimate
regional blood flow and oxygenation in tissues (14,
2 2 ) . I n t h e s t u d y, c h a n g e s i n s ke l e t a l m u s c l e b l o o d
perfusion under hypoxia and normoxia were monitored
by tissue hemoglobin level in triceps and quadriceps
muscles using NIRS. NIRS measurements were performed
using a frequency-domain tissue spectrometer
(ISS, Champaign, IL, USA), which includes two laser
diodes for measurement with wavelengths of 690 and
830 nm. The optodes were placed over the targeted
muscles with the sampling rate of 1 per second. NIRS
enables noninvasive continuous measurement of
changes in the concentration of oxygenated hemoglobin
( H b O 2 )
a n d
d e o x y g e n a t e d
h e m o g l o b i n
(deoxyHb). Changes in the tissue concentration of
total hemoglobin (THC) were calculated from the
sum of changes in HbO2 and deoxyHb, which is used
t o i n d i c a t e b l o o d d i s t r i b u t i o n f o r t h e p r e s e n t s t u d y.
Tissue oxygen saturation refers to the ratio of oxygenated
h e m o g l o b i n t o t o t a l h e m o g l o b i n i n t h e
microcirculation of a volume of illuminated tissue.
NIRS parameters were measured in micromolar units.
Glucose and Insulin
Plasma glucose and insulin were assessed during
NIRS measurement following 75-gram glucose ingestion
with
500
ml
of
tap
w a t e r.
Blood
samples
were
collected from the fingertip at 0 (fasting value), 30,
60 and 90 min. A glucose analyzer (Lifescan, Milpitas,
CA, USA) was utilized for glucose concentration
determination. Insulin was determined on the ELISA
a n a l y z e r ( Te c a n G e n i o s , S a l z b u r g , A u s t r i a ) ( 5 ) w i t h
the use of commercially available ELISA kits
( D i a g n o s t i c S y s t e m s L a b o r a t o r i e s , I n c . We b s t e r, T X ,
USA), according to the manufacture’s instruction.
Statistical Analysis
SPSS was used for all statistical analyses. Since
most of baseline mean values are statistically not
different, student t-test was used to distinguish the
mean between two trials for all measures. A level of
P < 0.05 was set for significance for all tests, and all
values are expressed as means ± standard deviation.
Results
The body composition data of swimmers measured
following the 3-week altitude training are shown
i n Ta b l e 1 . F o r t h e f i r s t e x p e r i m e n t , t h e b a s e l i n e a g e
and body composition between the swimmers and
control subjects were not significantly different (P >
0.05). The body mass and BMI of the swimmer and
control groups were not significantly altered before
a n d a f t e r t h e 3 - w e e k a l t i t u d e e x p o s u r e . H o w e v e r, t h e
subjects’ fat mass was significantly decreased and
lean mass was significantly increased to different
extents for all ten swimmers. The Control subjects
who resided at sea level for the same period of time
had no alterations on both measures using the same
DXA equipment, which demonstrated that the above
body composition changes after the altitude training
were not due to time variation of the measurements.
For the second experiment, arterial oxygen
saturation level after training was significantly lower
in the hypoxia trial than those in the control trial (Fig.
1). The hypoxia effect was well -reflected by significantly
greater blood lactate concentration above the control level (Fig. 2). Under the
fe d - cond itio n, glu co se an d in su lin leve ls in circulatio n we re bo th
elevated under the hypoxia condition after training
( F i g . 3 ) . To d e t e r m i n e w h e t h e r a l t i t u d e h y p o x i a w a s
the factor that caused the alterations in bod y composition
via glucose and insulin redistribut io n, the
hemoglobin changes in both the triceps and quadriceps
muscles under hypoxia were measured after glucose
ingestion (Figs. 4 and 5). We found that the hypoxia
exposure significantly increased total hemoglobin
(A) in the skeletal muscle above the normoxic level,
concurrently with greater saturation of tissue oxygen
(B) on both exercised muscles than in the normal air
e x p o s u re t r i a l . T h is i n c re a s e wa s p a ra l l e l e d w i t h ox y h e m o g l o b in
e l e v a t i o n ( C ) . F u r t h e r m o r e , h y p o x i a d i d
not cause changes in deoxy-hemoglobin levels (D).
Since autonomic nervous activity is directly
associated with peripheral vascular control, we also
determined vagal and sympathetic powers by HRV
measurement under hypoxia recovery conditions
(Fig. 6). Hypoxia did not affect vagal activity (high
f r e q u e n c y p o w e r, H P ) ( F i g . 6 A ) . I n c o n t r a s t , a s i g n i f i c a n t l y
increased sympathetic power (low frequency
to high frequency ratio) was observed under hypoxia
exposure (Fig. 6B).
Discussion
The present study provides evidence in human
subjects that altitude exposure can rapidly decrease
fat mass and increase lean mass in youth swimmers,
who maintained the same training volume at altitude
as at sea level. This fat-reducing effect of altitude
translocation occurred without noticeable changes in
body mass. Since the overall dietary intake was not
apparently changed, energy balance per se cannot be the reason to explain this
significant change. The evidence of body composition change is compelling,
as all ten swimmers demonstrated reciprocal decreases
in fat mass and increases in lean mass after the 3 -week
altitude exposure. The possibility that such a change
was due to an artifact caused by time -to-time variations
or regression to the mean (8) of DXA measurement
are precluded, as the body composition in the control
group was unchanged. The results of the study confirm
those of previous animal studies (6, 10) that
altitude hypoxia is an effective method to reduce
body fat without compromising or negatively affecting
lean mass.
During training recover y, we evaluated blood
distribution under glucose-ingested hyperinsulinemic
condition to mimic the postprandial state. A greater
insulin level above normoxic condition after oral
glucose challenge was observed, indicating that
moderate hypoxia caused a slight insulin resistance.
A similar finding has been reported elsewhere (26).
This condition can likely result in an increased perfusion
of both glucose and insulin preferentially into
the skeletal muscle according to our NIRS data.
Consistent with our observation, hypoxia has been
rep orted to in crease skeletal mu scle glu cose t ran sp ort
and vascular perfusion in rat muscles (30, 37). Considering
the large amount of muscle tissues in human
b o d y, t h i s c o n d i t i o n m a y e x p l a i n , t o s o m e e x t e n t ,
increased muscle mass in long -term altitude exposure.
We hypothesized that hypoxia was the major
contributor for the favorable change in body composition
during altitude translocation, based on wellest ablished
e v i d e n c e g a r n e r e d f r o m a n i m a l s t u d i e s
that a prolonged systemic hypoxia exposure decreased
body fat (6) and increased muscle mass (10). Oxygen
is the final acceptor of electron transport in fat
oxidation, yet the altitude environment has relativel y
lower oxygen availability than at sea level for fat
oxidation . Therefore, it is less likely that the observed
fat-reducing effects of altitude training were mediated
b y i n c r e a s e d f a t m e t a b o l i s m a t a l t i t u d e .
In
animals,
the
mechanism
of
increasing
fuel
acqui sit ion of the skeleta l mus cl e can lead to significant
reductions in body fat mass (1, 35). In this regard, for
t h e s e c o n d p a r t o f t h e s t u d y, w e h y p o t h e s i z e d t h a t t h e
fat-reducing effect was related to increased distribution
of insulin and energy subst rates towards skeletal muscles
in the swimmers. Our data, which showed hemoglobin
increases in the skeletal muscles, fit well with the
current finding of a reciprocal increase in lean mass
and a decrease in fat mass for all swimmers after 3
weeks of altitude training. Increasing insulin distribution
with more fuel supply into skeletal muscles
can promote fuel deposition and muscle growth, which
would in turn decrease fuel availability to adipose
tissues. Insulin is the major anabolic hormone released
after carbohydrate meals, which is able to stimulate
glu cose u ptake (25), glycogen synt hesis (4, 23), amin o
acid uptake (2), net protein synthesis (11), cell
proliferation (24) and triglyceride synthesis (29) in
both the skeletal muscle and adipose tissue (36).
Therefore, competition between the skeletal muscles
and adipose tissues for insulin-dependent fuel acquisition
plays a key role in regulating body composition.
I n t h e p r e s e n t s t u d y, h e m o g l o b i n c o n c e n t r a t i o n i n t h e
exercised skeletal muscles was monitored u nder a
hypoxia condition containing 16% oxygen. Using
NIRS measurement, our results showed that hypoxia
significantly elevated blood distribution to skeletal
muscles in the absence of increased rates of arterial
blood flow (BF). Although muscle BF has been
shown to be elevated under systemic hypoxia (17,
2 8 ) , i n t h e p r e s e n t s t u d y, n o s i g n i f i c a n t i n c r e a s e i n B F
was observed in both muscle groups with a relatively
less severe hypoxia. The vasodilatation that occurs in the skeletal
muscles during systemic hypoxia may function to
enhance tissue blood distribution to offset a deficit
in oxygen availability of the skeletal muscles (21,
3 0 ) . I n t r i g u i n g l y, m u s c l e t i s s u e o x y g e n s a t u ra t i o n ,
which generally mirrors the balance between oxygen
d e m a n d a n d s u p p l y, wa s e l e v a t e d i n t h e s u b j e c t s
u n d e r h y p o x i a r e c o v e r y. T h i s r e s u l t i s i n s o m e a g r e e m e n t
to the results of a study under a more severe
hypoxia condition (lowered SaO2 to 77 %) that muscle
tissue oxygen level was not lowered by hypoxia (34).
Since vascular supply is regulated, in part, by
the autonomic nervous system, the sympathetic and
vagal powers by HRV were measured. Results showed
that the sympathetic power was significantly elevated
in the subjects under hypoxia, which might play a role
in the regulation of body composition via altering
blood distribution among adipose and muscle tissues.
Similar results were reported under a different setting
during exercise (15, 17). The role of sympathetic activity
on body composition is also supported by the
evidence that a prolonged use of sympathomimetic
agent, such as clenbuterol, can lead to an increased
muscle mass concurrently with substantial reduction
in fat mass in rats (33) and humans (20). Therefore,
our results suggest that the change in body composition
is associated with an altered vascular control secondary
t o a n e l e v a t i o n i n s y m p a t h e t i c n e r v o u s a c t i v i t y. T h i s
change is expected to not only alter energy fuel distribution
but also to increase insulin delivery toward
the skeletal muscle. We interpret the da ta that fuel
redistribution under hypoxia conditions can also be
contributed by enhanced hepatic glucose output (19)
and enh an ced mu scle glu co se uptake (3 7 ) du e , in p art ,
to the increased sympathetic nervous stimulation.
It is surprising that the fat-reducing effect could
occur within such a short period of altitude exposure
(i.e. 3 weeks). Following exercise training, lipoprotein
lipase (LPL) is released from the vascular bed, and is,
therefore, redistributed in circulation (31). LPL is an
enzyme which functions to hydrolyze circulating
t r i g l y c e r i d e s fo r t i s s u e u p ta ke a n d sto ra g e . I t i s n o te wo r t hy
that these swimmers continued the same training
volume
at
altitude
as
at
sea
level.
The
increased
blood distribution in the skeletal muscle suggests that
LPL released from capillary bed, including the adipose
tissue, was accumulated towards muscle tissues to
facilitate fat deposition, while the adipose tissue
becomin g less likely to uptake circulatin g triglycerid es
due to competition between exercised muscle and
adipose tissues for circulating factors such as oxygen,
fuel and insulin. It has been shown that increasing
lipoprotein lipase activity in skeletal muscles is able
to decrease fat mass in training animals under the
same caloric intake and exercise training load (35).
I n t h i s st u d y, fat ma s s wa s red u c ed by 11 .4 %
and muscle mass only increased 1.5% (form pre -topost
altitude exposure). The small percent change in
muscle mass is in fact large in absolute terms, given
that muscle mass accounts for substantially a greater
portion of the human body relative to the adipose
tissue. Similar magnitude of reciprocal changes is
reported in another study that measured muscle and
adipose tissues directly in an exercise training setting
(35). In addition, increased total energy consumption
under hypoxia exposure (16) may also contribute to
a greater reduction in adiposity.
We note that swimming training at moderate altitude
can place swimmers under stressful conditions,
which might result in impairment of cognitive function
(5). More evaluation is warranted for designing a safer
training-recovery protocol. Furthermore, individual
variations against altitude exposure appear to vary
widely and are associated with baseline DHEA -S level
(27). It is current known that DHEA -S is also linked
with short-term body composition change (32). It
would be interesting to further determine the role
of DHEA-S in body composition changes during altitude
exposure.
In conclusion, swimmers are unique in having a
greater fat content than most types of athletes in other
sport disciplines. The current study presents an effective
intervention method to reduce fat mass and
increase muscle mass in youth swimmers. The reciprocal
decrease in fat mass and increase in lean mass
without a significant change in the body mass of the
swimmers occurred after 3 weeks of training at altitude.
Our evidence suggests that the preferential
redistributions of insulin and nutrients towards the
skeletal muscle under altitude hypoxia may be the k ey
underlying mechanisms for the reciprocal changes
in fat and lean mass of youth swimmers training at
altitude.
Acknowledgments
We would like to thank colleagues from the
N a n y a n g Te c h n o l o g i c a l U n i v e r s i t y i n S i n g a p o r e a n d
S h i h Hsi n Un i ve rsi t y i n Ta iwa n fo r t h e exce l l e nt
technical supports for the work. This research was
supported, in part, by a grant from National Science
C o u n c i l , Ta i wa n , g ra n t n u m b e r 1 0 1 - 2 6 2 2 - H - 1 5 4 - 0 0 1 CC2.
References
1. Argilés, J.M., Ló pez -Soriano, J., Almendro, V., Busque ts, S. and
López-Soriano, F.J. Cross -talk between skeletal muscle and adipose
t i s s u e : a l i n k w i t h o b e s i t y ? M e d . R e s . R e v. 2 5 : 4 9 - 6 5 , 2 0 0 5 .
2 . Bio lo, G., Williams, B.D., Fle min g , R.Y. an d Wo lfe , R.R. In su lin
action on muscle protein kinetics and amino acid transport during
r e c o v e r y a f t e r r e s i s t a n c e e xe rc i s e . D i a b e t e s 4 8 : 9 4 9 - 9 5 7 , 1 9 9 9 .
3. Bonen, A., Clark, M.G. and Henriksen, E.J. Experimental ap proaches in muscle
metabolism: hindlimb perfusion and isolated
muscle incubations. Am. J. Physiol. 266: E1 -E16, 1994.
4 . B o u s k i l a , M . , H i rs h m a n , M . F. , J e n s e n , J . , G o o d y e a r, L . J . a n d
S a ka m o to, K. In su lin p ro m o te s glyco ge n synt h e sis in the ab se n ce
o f GS K3 p h o sp h o r ylat io n in ske le tal mu scle . Am. J. P hysio l. 2 9 4 :
E28-E35, 2008.
5 . Ca o, L. J., Wan g , J., Hao, P.P., Su n , C.L. an d Che n , Y.G. Effe ct s
of ulinastatin, a urinary trypsin inhibitor, on synaptic plasticity and
s p a t i a l m e m o r y i n a rat m o d e l o f ce re b ra l i s c h e m i a / re p e r f u s i o n
injury. Chinese J. Physiol. 54: 435 -442, 2011.
6. Chen, C.Y., Tsai, Y.L., Kao, C.L., Lee, S.D., Wu, M.C., Mallikarjuna,
K . , Li a o, Y. H ., I v y, J. L . a n d Ku o, C . H. Ef fe c t o f m il d int e r mi tt e nt
hyp oxia o n glu co se to le ran ce , mu scle mo rp ho lo gy an d AM P KP GC 1α signaing. Chinese J. Physiol. 53: 62-71, 2010.
7. Chen, Y.L., Huang, C.Y., Lee, S.D., Chou, S.W., Hsieh, P.S., Hsieh,
C.C., Huang, Y.G. and Kuo, C.H. Discipline -specific insulin sensitivity
in athletes. Nutrition 25: 1137 -1142, 2009.
8. Chen, Y.L., Yeh, D.P., Lee, S.D. and Kuo, C.H. Regression to the
m e a n : e r r o r r e d u c t i o n v e rs u s b l o o d p r e s s u r e n o r m a l i z a t i o n b y
sports training. J. Sports. Sci. 29: 645-647, 2011.
9. Cruz-Jentoft, A.J., Baeyens, J.P., Bauer, J.M., Boirie, Y., Cederholm,
T. , L a n d i , F. , M a r t i n , F.C . , M i c h e l , J . - P. , Ro l l a n d , Y. , S c h n e i d e r,
S.M., Topinkova, E., Vandewoude, M. and Zamboni, M. Sarcopenia:
European consensus on definition and diagnosis. Age Ageing
39: 412-423, 2010.
10. Deveci, D., Marshall, J.M. and Egginton, S. Relationship between
capillary angiogenesis, fiber type, and fiber size in chronic systemic
hypoxia. Am. J. Physiol. Heart 281: H241-H252, 2001.
1 1 . Fe rran d o, A .A ., Ch in ke s, D.L., Wo lf, S.E ., M at in , S., He rn d o n ,
D.N . and Wo lfe, R.R. A sub maximal do se of in su lin p romote s n et
s ke l e t a l m u s c l e p ro t e in sy n t h e s i s i n p at i e n t s w i t h s e ve re b u r n s.
Ann. Surg. 229: 11-18, 1999.
12. Flynn, M.G., Costill, D.L., Kirwan, J.P., Mitchell, J.B., Houmard,
J . A . , F i n k , W. J . , B e l t g , J . D . a n d D ’A c q u i s t o , L . J . Fa t s t o r a g e i n
athletes: metabolic and hormonal res ponses to swimming and
running. Int. J. Sports Med. 11: 433-440, 1990.
13. Ghorbani, A., Varedi, M., Hadjzadeh, M. -Al. -R. and Omrani, G.
H. Type-1 diabetes induces depot -spe cific alterat ions in adipocyte
diameter and mass of adipose tissues in the rat. E xp. Clin. Endocrinol.
Diabetes. 118: 442-448, 2010.
14. Guenette, J.A., Vogiatzis, I., Zakynthinos, S., Athanasopoulos, D.,
K o s k o l o u , M . , G o l e m a t i , S . , V a s i l o p o u l o u , M . , W a g n e r, H . E . ,
R o u s s o s , C . , Wa g n e r, P. D . a n d B o u s h e l , R . H u m a n r e s p i r a t o r y
m u s c l e b l o o d f l o w m e a s u re d b y n e a r - i n f ra re d s p e c t ro s c o p y a n d
indocyanine green. J. Appl. Physiol. 104: 1202 -1210, 2008.
15. Hainsworth, R., Drinkhill, M. and Rivera -Chira, M. The autonomic
n e r vo u s system at h igh alt itu d e . Clin . Au ton o mic Re s. 17 : 1 3 - 1 9 ,
2007.
16. Hamad, N. and Travis, S.P.L. Weight loss at high altitude: pathophysiology
a n d p r a c t i c a l i m p l i c a t i o n s . E u r. J . G a s t r o e n t e r o l .
H e p a t o l .
1 8 :
5 - 1 0 ,
2 0 0 6 .
1 7 . He in o n e n , I. H., Ke mp p ain e n , J., Kask in o ro, K., Pe lto n e n , J.E .,
B o r r a , R . , L i n d r o o s , M . , O i k o n e n , V. , N u u t i l a , P. , K n u u t i , J . ,
B o u s h e l , R . a n d Ka l l i o ko s k i , K . K . Re g u l a t i o n o f h u m a n s ke l e t a l
muscle perfusion and its heterogeneity during exercise in moderate
hy p ox i a . A m . J. P h ys i o l . Re g u l . I n t e g r. C o m p . P hys i o l . 2 9 9 : R 7 2 R79, 2010.
18. Jang, K.T., Flynn, M.G., Costill, D.L., Kirwan, J.P., Houmard, J.A.,
M it c h e l l , J. B . an d D ’A c q u ist o, L . J. E n e rg y b a la n ce in co m p et it i ve
swimmers and runners. J. Swim. Res. 3: 19-23, 1987.
19. Jeong Hae, C., Min Jung, P., Kook Whan, K., Yoon Ha, C., Sun Hee,
P., Won Gun, A. and JaeHun, C. Molecular mechanism of hypoxiamediated
hepatic gluconeogenesis by transcriptional regulation.
FEBS Lett. 579: 2795-2801, 2005.
2 0 . Ka m a l a k k a n n a n , G . , P e t r i l l i , C . M . , G e o r g e , I . , L a M a n c a , J . ,
M c L a u g h l i n , B .T. , S h a n e , E . , M a n c i n i , D . M . a n d M a y b a u m , S .
Clenbuterol increases lean muscle mass but not endurance in
p a t i e n t s w i t h c h r o n i c h e a r t f a i l u r e . J . H e a r t L u n g Tr a n s p l a n t .
27: 457-461, 2008.
21. Korivi, M., Hou, C.W., Chen, C.Y., Lee, J.P., Kesireddy, S.R. and
Ku o, C . H. A n g i o ge n e s i s : Ro l e o f exe rc i s e t ra i n i n g a n d a g i n g .
Adapt. Med. 2: 29-41, 2010.
22. Kuebler, W.M., Sckell, A., Habler, O., Kleen, M., Kuhnle, G.E.H.,
Welte, M., Messmer, K. and Goetz, A.E. Noninvasive measurement
o f r e g i o n a l c e r e b ra l b l o o d f l o w b y n e a r - i n f r a r e d s p e c t r o s c o p y
and indocya nine green. J. Cereb. Bloo d Flow Metab. 18: 445 -456,
1998.
23. Kuo, C.H., Hwang, H., Lee, M.C., Castle, A.L. and Ivy, J.L. Role
of insul in on exerci se -i nduced GLUT -4 protein expres sion and
glycogen supercompensation in rat skeletal muscle. J. Appl. Physiol .
96: 621-627, 2004.
24. Kuo, W.-W., Chung, L.-C., Liu, C.-T., Wu, S.-P., Kuo, C.-H., Tsai,
F. - J . , Ts a i , C . - H . , L u , M . - C . , H u a n g , C . - Y. a n d L e e , S . - D . Ef f e c t s
of insulin replacement on cardiac apoptotic and survival pathways
in streptozotocin -induced diabetic rats. Cell Biochem. Funct.
27: 479-487, 2009.
2 5 . L ai , Y.C ., Za rrin p ash n e h , E . an d Je n se n , J. Ad d it i ve e ffe ct o f
co nt ract io n an d in su lin o n glu co se uptake an d glyco ge n synt h ase
in mu scle wit h d iffe rent glyco gen conte nt s. J. App l. Physiol. 1 08 :
1106-1115, 2010.
26. Larsen, J.J., Hansen, J.M., Olsen, N.V., Galbo, H. and Dela, F. The
effe ct of a lt itud e hyp ox ia o n g lu cos e h om eo stas i s i n m en . J.
Physiol. 504: 241-249, 1997.
2 7 . L e e , W.C . , C h e n , S . M . , Wu , M .C . , H o u , C .W. , L a i , Y.C . , L a i o,
Y.H., Lin , C.H. an d Ku o, C.H. T h e ro le o f d e hyd ro e piand ro ste ro n e
l e v e l s o n p h y s i o l o g i c a c c l i m at i z at i o n t o c h ro n i c m o u n t a i n e e r i n g
activity. High Alt. Med. Biol. 7: 228 -236, 2006.
2 8 . M a c L e a n , D . A . , S i n o w a y, L . I . a n d L e u e n b e r g e r, U . S y s t e m i c
hy p ox i a e l e vate s s ke l e ta l m u s c l e i nte rst i t i a l a d e no s i n e le ve l s
in humans. Circulation 98: 1990-1992, 1998.
2 9 . M ag ko s , F., Wan g , X. an d M itte nd o rfe r, B. M e tab o li c act i o n s
of insulin in men and women. Nutrition 26: 686 -693, 2010.
3 0 . M arsh al l, J.M . Ad e n o sin e an d mu sc le va so d ilat at io n in acu te
systemic hypoxia. Acta Physiol. Scand. 168: 561 -573, 2000.
31. Oscai, L.B., Tsika, R.W. and Essig, D.A. Exercise training has a
heparin -like effect on lipoprotein lipase activity in muscle. Can. J.
Physiol. Pharmacol. 70: 905-909, 1992.
32. Ostojic, S.M., Calleja, J. and Jourkesh, M. Effects of short -term
d e hyd ro e p ian d ro ste ro n e su p p le me ntat i o n o n b o d y co mp osit io n in
young athletes. Chinese J. Physiol. 53: 19 -25, 2010.
33. Pan, S.J., Hancock, J., Ding, Z., Fogt, D., Lee, M. and Ivy, J.L.
Ef f e c t s o f c l e n b u t e r o l o n i n s u l i n r e s i s t a n c e i n c o n s c i o u s o b e s e
Z u c ke r rat s . A m . J . P hys i o l . E n d o c r i n o l . M e t a b . 2 8 0 : E 5 5 4 - E 5 6 1 ,
2001.
34 . Pe ltonen , J.E ., Kowalchu k, J.M ., Paterson , D.H., D eLorey, D.S.,
d u M a n o i r, G . R . , P e t re l l a , R . J . a n d S h o e m a ke r, J . K . C e r e b ra l a n d
m u s c l e t i s s u e ox yge n at i o n i n a c u t e hy p ox i c ve nt i l at o r y re s p o n s e
t e s t . R e s p i r. P h y s i o l . N e u r o b i o l . 1 5 5 : 7 1 - 8 1 , 2 0 0 7 .
35. Suzuki, M., Doi, T., Lee, S.J., Okamura, K., Shimizu, S., Okano, G.,
Sato, Y., Shimomura, Y. and Fushiki, T. Effect of meal ti ming after
resistance exercise on hindlimb muscle mass and fat accumulation
i n t r a i n e d r a t s . J . N u t r. S c i . V i t a m i n o l . 4 5 : 4 0 1 - 4 0 9 , 1 9 9 9 .
3 6 . Tsen g , C.Y., Lai, Y.C. and Kuo, C.H. IGF -1 p art ially rep rodu ces
beneficial effect of exercise training on glucose t olerance in normal
r a t s .
A d a p t .
M e d .
3 :
1 1 2 - 1 1 8 ,
2 0 1 1 .
37. Zierath, J.R., Tsao, T.S., Stenbit, A.E., Ryder, J.W., Galuska, D. and
Cha rron, M.J. Re storation of hypoxia - stimu lated gluco se uptake in
GLUT4-deficient muscles by muscle -specific GLUT4 transgenic
complementation. J. Biol. Chem. 273: 20910 -20915, 1998.