Int J Sports Med 2015; 36(13): e24-e30
DOI: 10.1055/s-0035-1559715
Genetics & Molecular Biology
© Georg Thieme Verlag KG Stuttgart · New York

Exercise Training Improves Whole Body Insulin Resistance via Adiponectin Receptor 1

J.-K. Cho
1   School of Sport Science, Sungkyunkwan University, Suwon, Republic of Korea
,
S.-U. Kim
2   College of Engineering, Sangmyung University, Cheonan, Republic of Korea
,
H.-R. Hong
1   School of Sport Science, Sungkyunkwan University, Suwon, Republic of Korea
,
J.-H. Yoon
3   Department of Sports Science, Hannam University, Daejeon, Republic of Korea
,
H.-S. Kang
4   College of Sport Science, Sungkyunkwan University, Suwon, Republic of Korea
› Author Affiliations
Further Information

Publication History



accepted after revision 01 July 2015

Publication Date:
03 November 2015 (online)

Abstract

Little is known regarding whether adiponectin receptors mediate high-intensity interval training (HIT)-induced improvement of insulin resistance associated with obesity. This study investigated the effect of HIT on whole body insulin resistance in high-fat diet-induced obese mice. 5-week-old male mice (N=30) were randomly assigned to standard chow (SC) (n=10) or HFD (n=20) for 23 weeks. After 15 weeks of dietary treatment, the HFD mice were further assigned to HFD (n=10) or HFD plus HIT (HFD+HIT, n=10). The HFD+HIT mice were subjected to HIT during the last 8 weeks of the 23-week HFD course. HFD resulted in whole body insulin resistance, hypoadiponectinemia, suppressed expression of adiponectin receptor 1(AdipoR1) and 2 (AdipoR2), suppressed expression of phosphorylated AMP-activated protein kinase (p-AMPK) and NAD-dependent deacetylase sirtuin-1 (SIRT1), and decreased mRNAs of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferase I (CPT1), and acyl CoA oxidase (ACO) in skeletal muscle. In contrast, HIT alleviated whole body insulin resistance and prevented decreased levels of total adiponectin in both serum and adipose tissue. HIT also prevented the down-regulation of AdipoR1 and AMPK/SIRT1 proteins and the down-regulation of PPARα, CPT1, and ACO mRNAs. The current findings show that HIT alleviates whole body insulin resistance due to HFD-induced obesity via the AdipoR1 and AMPK/SIRT1 mediated-signaling pathway in skeletal muscle, implying the potential role of HIT to combat this metabolic condition.

 
  • References

  • 1 Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001; 7: 947-953
  • 2 Bergeron R, Ren JM, Cadman KS, Moore IK, Perret P, Pypaert M, Young LH, Semenkovich CF, Shulman GI. Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol 2001; 281: E1340-E1346
  • 3 Bruce CR, Thrush AB, Mertz VA, Bezaire V, Chabowski A, Heigenhauser GJ, Dyck DJ. Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am J Physiol 2006; 291: E99-E107
  • 4 Bruce CR, Hoy AJ, Turner N, Watt MJ, Allen TL, Carpenter K, Cooney GJ, Febbraio MA, Kraegen EW. Overexpression of carnitine palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance. Diabetes 2009; 58: 550-558
  • 5 Burgomaster KA, Cermak NM, Phillips SM, Benton CR, Bonen A, Gibala MJ. Divergent response of metabolite transport proteins in human skeletal muscle after sprint interval training and detraining. Am J Physiol 2007; 292: R1970-R1976
  • 6 Burgomaster KA, Howarth KR, Phillips SM, Rakobowchuk M, Macdonald MJ, McGee SL, Gibala MJ. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J Physiol 2008; 586: 151-160
  • 7 Ceddia RB, Somwar R, Maida A, Fang X, Bikopoulos G, Sweeney G. Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells. Diabetologia 2005; 48: 132-139
  • 8 Chang SP, Chen YH, Chang WC, Liu IM, Cheng JT. Increase of adiponectin receptor gene expression by physical exercise in soleus muscle of obese Zucker rats. Eur J Appl Physiol 2006; 97: 189-195
  • 9 Cho J, Kim S, Lee S, Kang H. Effect of Training Intensity on Nonalcoholic Fatty Liver Disease. Med Sci Sports Exerc 2014 Dec 23 [Epub ahead of print]
  • 10 Corton JM, Gillespie JG, Hardie DG. Role of the AMP-activated protein kinase in the cellular stress response. Curr Biol 1994; 4: 315-324
  • 11 Farias JM, Maggi RM, Tromm CB, Silva LA, Luciano TF, Marques SO, Lira FS, de Souza CT, Pinho RA. Exercise training performed simultaneously to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in mice. Lipids Health Dis 2012; 11: 134
  • 12 Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, Milne JC, Lambert PD, Mataki C, Elliott PJ, Auwerx J. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab 2008; 8: 347-358
  • 13 Felder TK, Hahne P, Soyal SM, Miller K, Höffinger H, Oberkofler H, Krempler F, Patsch W. Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans. Int J Obes (Lond) 2010; 34: 846-851
  • 14 Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98: 2005-2010
  • 15 Fujii N, Hayashi T, Hirshman MF, Smith JT, Habinowski SA, Kaijser L, Mu J, Ljungqvist O, Birnbaum MJ, Witters LA, Thorell A, Goodyear LJ. Exercise induces isoform-specific increase in 5’AMP-activated protein kinase activity in human skeletal muscle. Biochem Biophys Res Commun 2000; 273: 1150-1155
  • 16 Hafstad AD, Boardman NT, Lund J, Hagve M, Khalid AM, Wisløff U, Larsen TS, Aasum E. High intensity interval training alters substrate utilization and reduces oxygen consumption in the heart. J Appl Physiol 2011; 111: 1235-41
  • 17 Harriss DJ, Atkinson G. Ethical standards in sports and exercise science research: 2014 update. Int J Sports Med 2013; 34: 1025-1102
  • 18 Hawley JA, Lessard SJ. Exercise training-induced improvements in insulin action. Acta Physiol (Oxf) 2008; 192: 127-135
  • 19 Huang H, Iida KT, Sone H, Yokoo T, Yamada N, Ajisaka R. The effect of exercise training on adiponectin receptor expression in KKAy obese/diabetic mice. J Endocrinol 2006; 189: 643-653
  • 20 Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, Yamaguchi M, Namiki S, Nakayama R, Tabata M, Ogata H, Kubota N, Takamoto I, Hayashi YK, Yamauchi N, Waki H, Fukayama M, Nishino I, Tokuyama K, Ueki K, Oike Y, Ishii S, Hirose K, Shimizu T, Touhara K, Kadowaki T. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2 +) and AMPK/SIRT1. Nature 2010; 464: 1313-1319
  • 21 Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005; 26: 439-451
  • 22 Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006; 116: 1784-1792
  • 23 Kriketos AD, Gan SK, Poynten AM, Furler SM, Chisholm DJ, Campbell LV. Exercise increases adiponectin levels and insulin sensitivity in humans. Diabetes Care 2004; 27: 629-630
  • 24 Li G, Wang J, Ye J, Zhang Y, Zhang Y. PPARα protein expression was increased by four weeks of intermittent hypoxic training via AMPKα2-dependent manner in mouse skeletal muscle. PLoS One 2015; 10: e0122593
  • 25 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 1996; 221: 286-289
  • 26 Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002; 8: 731-737
  • 27 Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 2007; 450: 712-716
  • 28 Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem 1996; 120: 803-812
  • 29 Park DR, Park KH, Kim BJ, Yoon CS, Kim UH. Exercise ameliorates insulin resistance via Ca2+ signals distinct from those of insulin for GLUT4 translocation in skeletal muscles. Diabetes 2015; 64: 1224-1234
  • 30 Simpson KA, Singh MA. Effects of exercise on adiponectin: a systematic review. Obesity (Silver Spring) 2008; 16: 241-256
  • 31 Stutts WC. Physical activity determinants in adults. Perceived benefits, barriers, and self efficacy. AAOHN J 2002; 50: 499-507
  • 32 Weigert J, Neumeier M, Wanninger J, Wurm S, Kopp A, Schober F, Filarsky M, Schäffler A, Zeitoun M, Aslanidis C, Buechler C. Reduced response to adiponectin and lower abundance of adiponectin receptor proteins in type 2 diabetic monocytes. FEBS Lett 2008; 582: 1777-1782
  • 33 Whyte LJ, Gill JM, Cathcart AJ. Effect of 2 weeks of sprint interval training on health-related outcomes in sedentary overweight/obese men. Metabolism 2010; 59: 1421-1428
  • 34 Winder WW, Hardie DG. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol 1996; 270: E299-E304
  • 35 Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M, Holloszy JO. Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol 2000; 88: 2219-2226
  • 36 Wojtaszewski JF, Nielsen P, Hansen BF, Richter EA, Kiens B. Isoform-specific and exercise intensity-dependent activation of 5′-AMP-activated protein kinase in human skeletal muscle. J Physiol 2000; 528: 221-226
  • 37 Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423: 762-769
  • 38 Yamauchi T, Kadowaki T. Adiponectin receptor as a key player in healthy longevity and obesity-related diseases. Cell Metab 2013; 17: 185-196
  • 39 Yoon MJ, Lee GY, Chung JJ, Ahn YH, Hong SH, Kim JB. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor alpha. Diabetes 2006; 55: 2562-2570
  • 40 Zhang HH, Qin GJ, Li XL, Zhang YH, Du PJ, Zhang PY, Zhao YY, Wu J. SIRT1 overexpression in skeletal muscle in vivo induces increased insulin sensitivity and enhanced complex I but not complex II-V functions in individual subsarcolemmal and intermyofibrillar mitochondria. J Physiol Biochem 2015; 71: 177-190