Download PDF
Int J Sports Med 2006; 27(10): 786-791
DOI: 10.1055/s-2005-873020
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Short-term Training is Accompanied by a Down Regulation of ACC2 mRNA in Skeletal Muscle

V. B. Schrauwen-Hinderling1 , 2 , 5 , M. K. C. Hesselink2 , 4 , E. Moonen-Kornips2 , 3 , G. Schaart2 , 4 , M. E. Kooi1 , W. H. M. Saris2 , 3 , P. Schrauwen2 , 3
  • 1Department of Radiology, University Hospital Maastricht, Maastricht, The Netherlands
  • 2Nutrition and Toxicology Research Institute Maastricht, NUTRIM, Maastricht University, Maastricht, The Netherlands
  • 3Department of Human Biology, Maastricht University, Maastricht, The Netherlands
  • 4Department of Movement Sciences, Maastricht University, Maastricht, The Netherlands
  • 5Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
Further Information

Publication History

Accepted after revision: September 20, 2005

Publication Date:
01 February 2006 (online)

Also available at
    Permissions and Reprints

Abstract

Recently, we showed that short-term training induced a rapid increase in IMCL whilst insulin sensitivity tended to improve. Here we investigate molecular adaptations accompanying this physiological training-induced accumulation of IMCL. Nine untrained men (age: 23.3 ± 3.2 y; maximal power output: 3.8 ± 0.6 W/kg body weight) trained for two weeks. Before and after training, subjects cycled for three hours and biopsies were taken before and after exercise. mRNA concentrations of ACC2, HSL, LPL, Glut4 and HKII were quantified by RT‐PCR and association of Glut4 with the membrane was quantified by immunohistochemical method. Endurance training resulted in a decrease of 29.1 % in ACC2 mRNA (p = 0.02). After training, ACC2 mRNA tended to decrease with acute exercise (- 24.4 % [p = 0.06]). HSL mRNA decreased with acute exercise after training (- 37.3 % [p = 0.002]). LPL mRNA concentrations increased with acute exercise before training (+ 42.4 % [p = 0.05]) and HKII mRNA increased with acute exercise before (+ 72.5 % [p = 0.025]) and after training (+ 99.3 % [p = 0.05]). After acute exercise, more Glut4 was associated with the membrane than before exercise, but it was not affected by training. We conclude that the training-induced increase in IMCL was accompanied by molecular adaptations in muscle to improve fat oxidative capacity, while markers of glucose metabolism were not yet changed. The present data are in line with the hypothesis that the fat oxidative capacity might be more important than the IMCL content in determining insulin sensitivity.

Key words

Insulin sensitivity - fat oxidative capacity - intramuscular triglycerides (IMTG) - skeletal muscle

References

  • 1 Abu-Elheiga L, Matzuk M M, Abo-Hashema K A, Wakil S J. Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2.  Sci. 2001;  291 2613-2616
    CrossrefPubMedGoogle Scholar
  • 2 Abu-Elheiga L, Oh W, Kordari P, Wakil S J. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets.  Proc Natl Acad Sci USA. 2003;  100 10207-10212
    CrossrefPubMedGoogle Scholar
  • 3 Andreelli F, Laville M, Vega N, Riou J P, Vidal H. Regulation of gene expression during severe caloric restriction: lack of induction of p 85 alpha phosphatidylinositol 3-kinase mRNA in skeletal muscle of patients with type II (non-insulin-dependent) diabetes mellitus.  Diabetologia. 2000;  43 356-363
    CrossrefPubMedGoogle Scholar
  • 4 Auboeuf D, Vidal H. The use of the reverse transcription-competitive polymerase chain reaction to investigate the in vivo regulation of gene expression in small tissue samples.  Anal Biochem. 1997;  245 141-148
    CrossrefPubMedGoogle Scholar
  • 5 Bagby G J, Johnson J L, Bennett B W, Shepherd R E. Muscle lipoprotein lipase activity in voluntarily exercising rats.  J Appl Physiol. 1986;  60 1623-1627
    PubMedGoogle Scholar
  • 6 Baumann H, Jaggi M, Soland F, Howald H, Schaub M C. Exercise training induces transitions of myosin isoform subunits within histochemically typed human muscle fibres.  Pflugers Arch. 1987;  409 349-360
    PubMedGoogle Scholar
  • 7 Bergman B C, Butterfield G E, Wolfel E E, Casazza G A, Lopaschuk G D, Brooks G A. Evaluation of exercise and training on muscle lipid metabolism.  Am J Physiol. 1999;  276 E106-E117
    PubMedGoogle Scholar
  • 8 Bergstrom J, Hermansen L, Hultman E, Saltin B. Diet, muscle glycogen and physical performance.  Acta Physiol Scand. 1967;  71 140-150
    CrossrefPubMedGoogle Scholar
  • 9 Blaak E E, van Aggel-Leijssen D P, Wagenmakers A J, Saris W H, van Baak M A. Impaired oxidation of plasma-derived fatty acids in type 2 diabetic subjects during moderate-intensity exercise.  Diabetes. 2000;  49 2102-2107
    CrossrefPubMedGoogle Scholar
  • 10 Borghouts L B, Schaart G, Hesselink M K, Keizer H A. GLUT‐4 expression is not consistently higher in type-1 than in type-2 fibres of rat and human vastus lateralis muscles; an immunohistochemical study.  Pflugers Arch. 2000;  441 351-358
    PubMedGoogle Scholar
  • 11 Bruce C R, Anderson M J, Carey A L, Newman D G, Bonen A, Kriketos A D, Cooney G J, Hawley J A. Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status.  J Clin Endocrinol Metab. 2003;  88 5444-5451
    CrossrefPubMedGoogle Scholar
  • 12 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.  Anal Biochem. 1987;  162 156-159
    PubMedGoogle Scholar
  • 13 Decombaz J, Schmitt B, Ith M, Decarli B, Diem P, Kreis R, Hoppeler H, Boesch C. Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects.  Am J Physiol Regul Integr Comp Physiol. 2001;  281 R760-R769
    PubMedGoogle Scholar
  • 14 Dresner A, Laurent D, Marcucci M, Griffin M E, Dufour S, Cline G W, Slezak L A, Andersen D K, Hundal R S, Rothman D L, Petersen K F, Shulman G I. Effects of free fatty acids on glucose transport and IRS‐1-associated phosphatidylinositol 3-kinase activity.  J Clin Invest. 1999;  103 253-259
    CrossrefPubMedGoogle Scholar
  • 15 Enevoldsen L H, Stallknecht B, Langfort J, Petersen L N, Holm C, Ploug T, Galbo H. The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle.  J Physiol. 2001;  536 871-877
    CrossrefPubMedGoogle Scholar
  • 16 Goodpaster B H, He J, Watkins S, Kelley D E. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes.  J Clin Endocrinol Metab. 2001;  86 5755-5761
    CrossrefPubMedGoogle Scholar
  • 17 Gulve E A, Spina R J. Effect of 7 - 10 days of cycle ergometer exercise on skeletal muscle GLUT‐4 protein content.  J Appl Physiol. 1995;  79 1562-1566
    PubMedGoogle Scholar
  • 18 Harris J A, Benedict F G. A Biometric Study of Basal Metabolism in Man. Washington; Carnegie Institution of Washington 1919
    Google Scholar
  • 19 Hoppeler H, Howald H, Conley K, Lindstedt S L, Claassen H, Vock P, Weibel E R. Endurance training in humans: aerobic capacity and structure of skeletal muscle.  J Appl Physiol. 1985;  59 320-327
    PubMedGoogle Scholar
  • 20 Houmard J A, Shinebarger M H, Dolan P L, Leggett-Frazier N, Bruner R K, McCammon M R, Israel R G, Dohm G L. Exercise training increases GLUT‐4 protein concentration in previously sedentary middle-aged men.  Am J Physiol. 1993;  264 E896-E901
    PubMedGoogle Scholar
  • 21 Hurley B F, Nemeth P M, Martin 3rd W H, Hagberg J M, Dalsky G P, Holloszy J O. Muscle triglyceride utilization during exercise: effect of training.  J Appl Physiol. 1986;  60 562-567
    PubMedGoogle Scholar
  • 22 Ingjer F. Effects of endurance training on muscle fibre ATP‐ase activity, capillary supply and mitochondrial content in man.  J Physiol. 1979;  294 419-432
    PubMedGoogle Scholar
  • 23 Jacob S, Machann J, Rett K, Brechtel K, Volk A, Renn W, Maerker E, Matthaei S, Schick F, Claussen C D, Haring H U. Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.  Diabetes. 1999;  48 1113-1119
    PubMedGoogle Scholar
  • 24 Kelley D E, Mandarino L J. Fuel selection in human skeletal muscle in insulin resistance: a reexamination.  Diabetes. 2000;  49 677-683
    CrossrefPubMedGoogle Scholar
  • 25 Kraniou Y, Cameron-Smith D, Misso M, Collier G, Hargreaves M. Effects of exercise on GLUT‐4 and glycogenin gene expression in human skeletal muscle.  J Appl Physiol. 2000;  88 794-796
    PubMedGoogle Scholar
  • 26 Kristiansen S, Gade J, Wojtaszewski J F, Kiens B, Richter E A. Glucose uptake is increased in trained vs. untrained muscle during heavy exercise.  J Appl Physiol. 2000;  89 1151-1158
    PubMedGoogle Scholar
  • 27 Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel S M, Rothman D L, Roden M, Shulman G I. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.  Diabetologia. 1999;  42 113-116
    CrossrefPubMedGoogle Scholar
  • 28 Langfort J, Donsmark M, Ploug T, Holm C, Galbo H. Hormone-sensitive lipase in skeletal muscle: regulatory mechanisms.  Acta Physiol Scand. 2003;  178 397-403
    CrossrefPubMedGoogle Scholar
  • 29 Laville M, Auboeuf D, Khalfallah Y, Vega N, Riou J P, Vidal H. Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle.  J Clin Invest. 1996;  98 43-49
    PubMedGoogle Scholar
  • 30 Levak-Frank S, Radner H, Walsh A, Stollberger R, Knipping G, Hoefler G, Sattler W, Weinstock P H, Breslow J L, Zechner R. Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice.  J Clin Invest. 1995;  96 976-986
    PubMedGoogle Scholar
  • 31 Martin 3rd W H. Effects of acute and chronic exercise on fat metabolism.  Exerc Sport Sci Rev. 1996;  24 203-231
    PubMedGoogle Scholar
  • 32 Millet L, Vidal H, Andreelli F, Larrouy D, Riou J P, Ricquier D, Laville M, Langin D. Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans.  J Clin Invest. 1997;  100 2665-2670
    CrossrefPubMedGoogle Scholar
  • 33 Oscai L B, Caruso R A, Wergeles A C. Lipoprotein lipase hydrolyzes endogenous triacylglycerols in muscle of exercised rats.  J Appl Physiol. 1982;  52 1059-1063
    PubMedGoogle Scholar
  • 34 Pan D A, Lillioja S, Kriketos A D, Milner M R, Baur L A, Bogardus C, Jenkins A B, Storlien L H. Skeletal muscle triglyceride levels are inversely related to insulin action.  Diabetes. 1997;  46 983-988
    PubMedGoogle Scholar
  • 35 Perdomo G, Commerford S R, Richard A M, Adams S H, Corkey B E, O'Doherty R M, Brown N F. Increased beta-oxidation in muscle cells enhances insulin-stimulated glucose metabolism and protects against fatty acid-induced insulin resistance despite intramyocellular lipid accumulation.  J Biol Chem. 2004;  279 27177-27186
    CrossrefPubMedGoogle Scholar
  • 36 Phillips S M, Han X X, Green H J, Bonen A. Increments in skeletal muscle GLUT‐1 and GLUT‐4 after endurance training in humans.  Am J Physiol. 1996;  270 E456-E462
    PubMedGoogle Scholar
  • 37 Richter E A, Jensen P, Kiens B, Kristiansen S. Sarcolemmal glucose transport and GLUT‐4 translocation during exercise are diminished by endurance training.  Am J Physiol. 1998;  274 E89-E95
    PubMedGoogle Scholar
  • 38 Schmitt B, Fluck M, Decombaz J, Kreis R, Boesch C, Wittwer M, Graber F, Vogt M, Howald H, Hoppeler H. Transcriptional adaptations of lipid metabolism in tibialis anterior muscle of endurance-trained athletes.  Physiol Genomics. 2003;  15 148-157
    PubMedGoogle Scholar
  • 39 Schrauwen P, van Aggel-Leijssen D P, Hul G, Wagenmakers A J, Vidal H, Saris W H, van Baak M A. The effect of a 3-month low-intensity endurance training program on fat oxidation and acetyl-CoA carboxylase-2 expression.  Diabetes. 2002;  51 2220-2226
    CrossrefPubMedGoogle Scholar
  • 40 Schrauwen-Hinderling V B, Schrauwen P, Hesselink M K, van Engelshoven J M, Nicolay K, Saris W H, Kessels A G, Kooi M E. The increase in intramyocellular lipid content is a very early response to training.  J Clin Endocrinol Metab. 2003;  88 1610-1616
    CrossrefPubMedGoogle Scholar
  • 41 Watt M J, Heigenhauser G J, O'Neill M, Spriet L L. Hormone-sensitive lipase activity and fatty acyl-CoA content in human skeletal muscle during prolonged exercise.  J Appl Physiol. 2003;  95 314-321
    PubMedGoogle Scholar

Vera B. Schrauwen-Hinderling

Department of Radiology, University Hospital Maastricht

P. O. Box 5800

6202 AZ Maastricht

The Netherlands

Phone: + 31433874951/10

Fax: + 31 4 33 87 69 09

Email: vhi@rdia.azm.nl

      >