Abstract
Moderate-intensity exercise at the lactate threshold (LT) is considered to be a safe
and effective training regimen for improving metabolic syndrome. The aim of the current
study was to investigate the effects of moderate exercise performed at the LT on skeletal
muscle gene expression. 6 healthy men participated in cycle ergometer training at
LT, 60 min/d, 5 d/wk for 12 wks. Muscle samples were collected after 5 d of training,
and then 2 d after training at wks 6 and 12. Quantitative real-time PCR analysis revealed
that the expression of peroxisome proliferator activated receptor co-activated 1α
was significantly increased at 1 h after the training session on day 5. Moreover,
using serial analysis gene expression, we found that moderate training for 6 and 12
wks simultaneously induced the expression of a number of metabolic genes involved
in the TCA cycle, β-oxidation, and electron transport. Furthermore, several genes
encoding antioxidant enzymes and contractile apparatus were induced. The expression
levels of 233 novel transcripts were also altered in response to moderate exercise.
Thus, moderate training at the LT is a sufficient stimulus to induce the expression
of numerous genes implicated in the development of metabolic syndrome, transcripts
involved in the contractile apparatus, and novel transcripts.
Key words
lactate threshold - metabolism - skeletal muscle - transcriptome
References
1
Optimum physical performance capacity in adults: Report of a WHO Scientific Group.
World Health Organ Tech Rep Ser.
1969;
436
1-32
2
Akamine R, Yamamoto T, Watanabe M, Yamazaki N, Kataoka M, Ishikawa M, Ooie T, Baba Y,
Shinohara Y.
Usefulness of the 5′ region of the cDNA encoding acidic ribosomal phosphoprotein P0
conserved among rats, mice, and humans as a standard probe for gene expression analysis
in different tissues and animal species.
J Biochem Biophys Methods.
2007;
70
481-486
3
Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J,
Rangwala SM, Baek KH, Rosenzweig A, Spiegelman BM.
HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator
PGC-1alpha.
Nature.
2008;
451
1008-1012
4
Essen B, Hagenfeldt L, Kaijser L.
Utilization of blood-borne and intramuscular substrates during continuous and intermittent
exercise in man.
J Physiol.
1977;
265
489-506
5
Goldman RF, Buskirk ER.
A method for underwater weighing and the determination of body density.
In Techniques for Measuring Body Composition.
Brozek J, Hershel A (eds).
1961;
78-89
6
Harriss DJ, Atkinson G.
International Journal of Sports Medicine – Ethical Standards in Sport and Exercise
Science Research.
Int J Sports Med.
2009;
30
701-702
7
Hittel DS, Kraus WE, Tanner CJ, Houmard JA, Hoffman EP.
Exercise training increases electron and substrate shuttling proteins in muscle of
overweight men and women with the metabolic syndrome.
J Appl Physiol.
2005;
98
168-179
8
Knoll KE, Pietrusz JL, Liang M.
Tissue-specific transcriptome responses in rats with early streptozotocin-induced
diabetes.
Physiol Genomics.
2005;
21
222-229
9
Kraus WE, Torgan CE, Duscha BD, Norris J, Brown SA, Cobb FR, Bales CW, Annex BH, Samsa GP,
Houmard JA, Slentz CA.
Studies of a targeted risk reduction intervention through defined exercise (STRRIDE).
Med Sci Sports Exerc.
2001;
33
1774-1784
10
Lash AE, Tolstoshev CM, Wagner L, Schuler GD, Strausberg RL, Riggins GJ, Altschul SF.
SAGEmap: a public gene expression resource.
Genome Res.
2000;
10
1051-1060
11
Lillioja S, Young AA, Culter CL, Ivy JL, Abbott WG, Zawadzki JK, Yki-Jarvinen H, Christin L,
Secomb TW, Bogardus C.
Skeletal muscle capillary density and fiber type are possible determinants of in vivo
insulin resistance in man.
J Clin Invest.
1987;
80
415-424
12
Miyake K, Ogawa W, Matsumoto M, Nakamura T, Sakaue H, Kasuga M.
Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition
of phosphoinositide 3-kinase signaling in the liver.
J Clin Invest.
2002;
110
1483-1491
13
Motoyama M, Sunami Y, Kinoshita F, Irie T, Sasaki J, Arakawa K, Kiyonaga A, Tanaka H,
Shindo M.
The effects of long-term low intensity aerobic training and detraining on serum lipid
and lipoprotein concentrations in elderly men and women.
Eur J Appl Physiol.
1995;
70
126-131
14
Motoyama M, Sunami Y, Kinoshita F, Kiyonaga A, Tanaka H, Shindo M, Irie T, Urata H,
Sasaki J, Arakawa K.
Blood pressure lowering effect of low intensity aerobic training in elderly hypertensive
patients.
Med Sci Sports Exerc.
1998;
30
818-823
15
Nishida Y, Higaki Y, Tokuyama K, Fujimi K, Kiyonaga A, Shindo M, Sato Y, Tanaka H.
Effect of mild exercise training on glucose effectiveness in healthy men.
Diabetes Care.
2001;
24
1008-1013
16
Nishida Y, Tokuyama K, Nagasaka S, Higaki Y, Shirai Y, Kiyonaga A, Shindo M, Kusaka I,
Nakamura T, Ishibashi S, Tanaka H.
Effect of moderate exercise training on peripheral glucose effectiveness, insulin
sensitivity, and endogenous glucose production in healthy humans estimated by a 2-compartment-labeled
minimal model.
Diabetes.
2004;
53
315-320
17
O’Neill DS, Zheng D, Anderson WK, Dohm GL, Houmard JA.
Effect of endurance exercise on myosin heavy chain gene regulation in human skeletal
muscle.
Am J Physiol.
1999;
276
R414-R419
18
Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I,
Costello M, Saccone R, Landaker EJ, Goldfine AB, Mun E, DeFronzo R, Finlayson J, Kahn CR,
Mandarino LJ.
Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance
and diabetes: Potential role of PGC1 and NRF1.
Proc Natl Acad Sci USA.
2003;
100
8466-8471
19
Pilegaard H, Saltin B, Neufer PD.
Exercise induces transient transcriptional activation of the PGC-1alpha gene in human
skeletal muscle.
J Physiol.
2003;
546
851-858
20
Puigserver P, Spiegelman BM.
Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha):
transcriptional coactivator and metabolic regulator.
Endocr Rev.
2003;
24
78-90
21
Radom-Aizik S, Hayek S, Shahar I, Rechavi G, Kaminski N, Ben-Dov I.
Effects of aerobic training on gene expression in skeletal muscle of elderly men.
Med Sci Sports Exerc.
2005;
37
1680-1696
22
Russell AP, Feilchenfeldt J, Schreiber S, Praz M, Crettenand A, Gobelet C, Meier CA,
Bell DR, Kralli A, Giacobino JP, Deriaz O.
Endurance training in humans leads to fiber type-specific increases in levels of peroxisome
proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated
receptor-alpha in skeletal muscle.
Diabetes.
2003;
52
2874-2881
23
Russell AP, Hesselink MK, Lo SK, Schrauwen P.
Regulation of metabolic transcriptional co-activators and transcription factors with
acute exercise.
FASEB J.
2005;
19
986-988
24
Schiaffino S, Reggiani C.
Molecular diversity of myofibrillar proteins: gene regulation and functional significance.
Physiol Rev.
1996;
76
371-423
25
Schneider DA, McGuiggin ME, Kamimori GH.
A comparison of the blood lactate and plasma catecholamine thresholds in untrained
male subjects.
Int J Sports Med.
1992;
13
562-566
26
Shono N, Urata H, Saltin B, Mizuno M, Harada T, Shindo M, Tanaka H.
Effects of low intensity aerobic training on skeletal muscle capillary and blood lipoprotein
profiles.
J Atheroscler Thromb.
2002;
9
78-85
27
Short KR, Vittone JL, Bigelow ML, Proctor DN, Coenen-Schimke JM, Rys P, Nair KS.
Changes in myosin heavy chain mRNA and protein expression in human skeletal muscle
with age and endurance exercise training.
J Appl Physiol.
2005;
99
95-102
28
Sriwijitkamol A, Coletta DK, Wajcberg E, Balbontin GB, Reyna SM, Barrientes J, Eagan PA,
Jenkinson CP, Cersosimo E, DeFronzo RA, Sakamoto K, Musi N.
Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type
2 diabetes: a time-course and dose-response study.
Diabetes.
2007;
56
836-848
29
St-Amand J, Okamura K, Matsumoto K, Shimizu S, Sogawa Y.
Characterization of control and immobilized skeletal muscle: an overview from genetic
engineering.
FASEB J.
2001;
15
684-692
30
Sunami Y, Motoyama M, Kinoshita F, Mizooka Y, Sueta K, Matsunaga A, Sasaki J, Tanaka H,
Shindo M.
Effects of low-intensity aerobic training on the high-density lipoprotein cholesterol
concentration in healthy elderly subjects.
Metabolism.
1999;
48
984-988
31
Teran-Garcia M, Rankinen T, Koza RA, Rao DC, Bouchard C.
Endurance training-induced changes in insulin sensitivity and gene expression.
Am J Physiol.
2005;
288
E1168-E1178
32
Velculescu VE, Zhang L, Vogelstein B, Kinzler KW.
Serial analysis of gene expression.
Science.
1995;
270
484-487
33
Venables MC, Achten J, Jeukendrup AE.
Determinants of fat oxidation during exercise in healthy men and women: a cross-sectional
study.
J Appl Physiol.
2005;
98
160-167
34
Yoshioka M, Tanaka H, Shono N, Shindo M, St-Amand J.
Gene expression profile of sprinter's muscle.
Int J Sports Med.
2007;
28
1053-1058
35
Zierath JR, Hawley JA.
Skeletal muscle fiber type: influence on contractile and metabolic properties.
PLoS Biol.
2004;
2
e348
Correspondence
Dr. Yuichiro Nishida
Saga University
Department of Preventive
Medicine
Faculty of Medicine
5-1-1 Nabeshima
849-8501 Saga
Japan
Telefon: +81/952/34 2287
Fax: +81/952/34 2065
eMail: ynishida@cc.saga-u.ac.jp