Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 302, Issue 3, 2012, Pages

  Hoshino, Daisuke ^a   Yoshida, Yuko ^b   Holloway, Graham P ^b   Lally, James ^b   Hatta, Hideo ^a   Bonen, Arend ^b  

^a UNIVERSITY OF TOKYO   (Japan)

^b UNIVERSITY OF GUELPH   (Canada)

Author keywords

Mitochondria; Oxidative capacity

Indexed keywords

3 HYDROXYACYL COENZYME A DEHYDROGENASE; CD36 ANTIGEN; CITRATE SYNTHASE; CLENBUTEROL; CYTOCHROME C OXIDASE; FATTY ACID; GLUCOSE TRANSPORTER 4; LACTATE DEHYDROGENASE; MONOCARBOXYLATE TRANSPORTER 1; PALMITIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PYRUVIC ACID; RECEPTOR INTERACTING PROTEIN 140;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; ENZYME ACTIVITY; FATTY ACID METABOLISM; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; GLUCOSE TRANSPORT; MALE; MITOCHONDRION; MUSCLE MASS; NONHUMAN; PRIORITY JOURNAL; RAT; SKELETAL MUSCLE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADRENERGIC BETA-2 RECEPTOR AGONISTS; ANIMALS; CLENBUTEROL; DOWN-REGULATION; FATTY ACIDS; MALE; MITOCHONDRIA, MUSCLE; MITOCHONDRIAL PROTEINS; MODELS, ANIMAL; MUSCLE PROTEINS; MUSCLE, SKELETAL; NUCLEAR PROTEINS; OXIDATION-REDUCTION; PALMITATES; PYRUVATES; RATS; RATS, SPRAGUE-DAWLEY; RNA-BINDING PROTEINS; TRANSCRIPTION FACTORS; UP-REGULATION;

EID: 84856995221     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00183.2011     Document Type: Article

References (70)

1. Au DH, Lemaitre RN, Curtis JR, Smith NL, Psaty BM. The risk of myocardial infarction associated with inhaled beta-adrenoceptor agonists. Am J Respir Crit Care Med 161: 827-830, 2000.
2. Benson DW, Foley-Nelson T, Chance WT, Zhang FS, James JH, Fischer JE. Decreased myofibrillar protein breakdown following treatment with clenbuterol. J Surg Res 50: 1-5, 1991.
3. Benton CR, Campbell SE, Tonouchi M, Hatta H, Bonen A. Monocarboxylate transporters in subsarcolemmal and intermyofibrillar mitochondria. Biochem Biophys Res Commun 323: 249-253, 2004.
4. Benton CR, Holloway GP, Campbell SE, Yoshida Y, Tandon NN, Glatz JF, Luiken JJ, Spriet LL, Bonen A. Rosiglitazone increases fatty acid oxidation and fatty acid translocase (FAT/CD36) but not carnitine palmitoyltransferase I in rat muscle mitochondria. J Physiol 586: 1755-1766, 2008.
5. Benton CR, Holloway GP, Han XX, Yoshida Y, Snook LA, Lally J, Glatz JF, Luiken JJ, Chabowski A, Bonen A. Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1alpha) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats. Diabetologia 53: 2008-2019, 2010.
6. Benton CR, Nickerson JG, Lally J, Han XX, Holloway GP, Glatz JF, Luiken JJ, Graham TE, Heikkila JJ, Bonen A. Modest PGC-1alpha overexpression in muscle in vivo is sufficient to increase insulin sensitivity and palmitate oxidation in subsarcolemmal, not intermyofibrillar, mitochondria. J Biol Chem 283: 4228-4240, 2008.
7. Benton CR, Yoshida Y, Lally J, Han XX, Hatta H, Bonen A. PGC-1alpha increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4. Physiol Genomics 35: 45-54, 2008.
8. Bergmeyer HU. Methods in Enzymatic Analysis. New York: Verlag Chemie Weinheim, 1974.
9. Bizeau ME, Willis WT, Hazel JR. Differential responses to endurance training in subsarcolemmal and intermyofibrillar mitochondria. J Appl Physiol 85: 1279-1284, 1998.
10. Bonen A. The expression of lactate transporters (MCT1 and MCT4) in heart and muscle. Eur J Appl Physiol 86: 6-11, 2001.
11. Bonen A, Miskovic D, Tonouchi M, Lemieux K, Wilson MC, Marette A, Halestrap AP. Abundance and subcellular distribution of MCT1 and MCT4 in heart and fast-twitch skeletal muscles. Am J Physiol Endocrinol Metab 278: E1067-E1077, 2000.
12. Bonnet N, Benhamou CL, Brunet-Imbault B, Arlettaz A, Horcajada MN, Richard O, Vico L, Collomp K, Courteix D. Severe bone alterations under beta2 agonist treatments: bone mass, microarchitecture and strength analyses in female rats. Bone 37: 622-633, 2005.
13. Campbell SE, Tandon NN, Woldegiorgis G, Luiken JJ, Glatz JF, Bonen A. A novel function for fatty acid translocase (FAT)/CD36: involvement in long chain fatty acid transfer into the mitochondria. J Biol Chem 279: 36235-36241, 2004.
14. Castle A, Yaspelkis BB, 3rd Kuo CH, Ivy JL. Attenuation of insulin resistance by chronic beta2-adrenergic agonist treatment possible muscle specific contributions. Life Sci 69: 599-611, 2001.
15. Dimmer KS, Friedrich B, Lang F, Deitmer JW, Broer S. The lowaffinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J 350: 219-227, 2000.
16. Duncan ND, Williams DA, Lynch GS. Deleterious effects of chronic clenbuterol treatment on endurance and sprint exercise performance in rats. Clin Sci (Lond) 98: 339-347, 2000.
17. Fritah A, Christian M, Parker MG. The metabolic coregulator RIP140: an update. Am J Physiol Endocrinol Metab 299: E335-E340, 2010.
18. Glatz JF, Jacobs AE, Veerkamp JH. Fatty acid oxidation in human and rat heart. Comparison of cell-free and cellular systems. Biochim Biophys Acta 794: 454-465, 1984.
19. Goncalves DA, Lira EC, Baviera AM, Cao P, Zanon NM, Arany Z, Bedard N, Tanksale P, Wing SS, Lecker SH, Kettelhut IC, Navegantes LC. Mechanisms involved in 3=,5=-cyclic adenosine monophosphatemediated inhibition of the ubiquitin-proteasome system in skeletal muscle. Endocrinology 150: 5395-5404, 2009.
20. Gurd BJ, Perry CG, Heigenhauser GJ, Spriet LL, Bonen A. Highintensity interval training increases SIRT1 activity in human skeletal muscle. Appl Physiol Nutr Metab 35: 350-357, 2010.
21. Hallberg M, Morganstein DL, Kiskinis E, Shah K, Kralli A, Dilworth SM, White R, Parker MG, Christian M. A functional interaction between RIP140 and PGC-1alpha regulates the expression of the lipid droplet protein CIDEA. Mol Cell Biol 28: 6785-6795, 2008.
22. Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK, Yan Z, Spiegelman BM. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J Biol Chem 282: 30014-30021, 2007.
23. Handschin C, Rhee J, Lin J, Tarr PT, Spiegelman BM. An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proc Natl Acad Sci USA 100: 7111-7116, 2003.
24. Higashida K, Higuchi M, Terada S. Potential role of lipin-1 in exerciseinduced mitochondrial biogenesis. Biochem Biophys Res Commun 374: 587-591, 2008.
25. Holloway GP, Benton CR, Mullen KL, Yoshida Y, Snook LA, Han XX, Glatz JF, Luiken JJ, Lally J, Dyck DJ, Bonen A. In obese rat muscle transport of palmitate is increased and is channeled to triacylglycerol storage despite an increase in mitochondrial palmitate oxidation. Am J Physiol Endocrinol Metab 296: E738-E747, 2009.
26. Holloway GP, Gurd BJ, Snook LA, Lally J, Bonen A. Compensatory increases in nuclear PGC1alpha protein are primarily associated with subsarcolemmal mitochondrial adaptations in ZDF rats. Diabetes 59: 819-828, 2010.
27. Holloway GP, Jain SS, Bezaire V, Han XX, Glatz JF, Luiken JJ, Harper ME, Bonen A. FAT/CD36-null mice reveal that mitochondrial FAT/CD36 is required to upregulate mitochondrial fatty acid oxidation in contracting muscle. Am J Physiol Regul Integr Comp Physiol 297: R960-R967, 2009.
28. Holloway GP, Lally J, Nickerson JG, Alkhateeb H, Snook LA, Heigenhauser GJ, Calles-Escandon J, Glatz JF, Luiken JJ, Spriet LL, Bonen A. Fatty acid binding protein facilitates sarcolemmal fatty acid transport but not mitochondrial oxidation in rat and human skeletal muscle. J Physiol 582: 393-405, 2007.
29. Holloway GP, Luiken JJ, Glatz JF, Spriet LL, Bonen A. Contribution of FAT/CD36 to the regulation of skeletal muscle fatty acid oxidation: an overview. Acta Physiol (Oxf) 194: 293-309, 2008.
30. Holloway GP, Snook LA, Harris RJ, Glatz JF, Luiken JJ, Bonen A. In obese Zucker rats, lipids accumulate in the heart despite normal mitochondrial content, morphology and long-chain fatty acid oxidation. J Physiol 589: 169-180, 2011.
31. Hood DA. Contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 90: 1137-1157, 2001.
32. Ingalls CP, Barnes WS, Smith SB. Interaction between clenbuterol and run training: effects on exercise performance and MLC isoform content. J Appl Physiol 80: 795-801, 1996.
33. Joubert R, Metayer Coustard S, Swennen Q, Sibut V, Crochet S, Cailleau-Audouin E, Buyse J, Decuypere E, Wrutniak-Cabello C, Cabello G, Tesseraud S, Collin A. The beta-adrenergic system is involved in the regulation of the expression of avian uncoupling protein in the chicken. Domest Anim Endocrinol 38: 115-125, 2010.
34. Kiilerich K, Adser H, Jakobsen AH, Pedersen PA, Hardie DG, Wojtaszewski JF, Pilegaard H. PGC-1α increases PDH content but does not change acute PDH regulation in mouse skeletal muscle. Am J Physiol Regul Integr Comp Physiol 299: R1350-R1359, 2010.
35. Kitaura T, Tsunekawa N, Hatta H. Decreased monocarboxylate transporter 1 in rat soleus and EDL muscles exposed to clenbuterol. J Appl Physiol 91: 85-90, 2001.
36. Koonen DP, Benton CR, Arumugam Y, Tandon NN, Calles-Escandon J, Glatz JF, Luiken JJ, Bonen A. Different mechanisms can alter fatty acid transport when muscle contractile activity is chronically altered. Am J Physiol Endocrinol Metab 286: E1042-E1049, 2004.
37. Koves TR, Noland RC, Bates AL, Henes ST, Muoio DM, Cortright RN. Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism. Am J Physiol Cell Physiol 288: C1074-C1082, 2005.
38. Kuo CH, Ding Z, Ivy JL. Interaction of exercise training and clenbuterol on GLUT-4 protein in muscle of obese Zucker rats. Am J Physiol Endocrinol Metab 271: E847-E854, 1996.
39. Lee WJ, Kim M, Park HS, Kim HS, Jeon MJ, Oh KS, Koh EH, Won JC, Kim MS, Oh GT, Yoon M, Lee KU, Park JY. AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochem Biophys Res Commun 340: 291-295, 2006.
40. Lehman JJ, Boudina S, Banke NH, Sambandam N, Han X, Young DM, Leone TC, Gross RW, Lewandowski ED, Abel ED, Kelly DP. The transcriptional coactivator PGC-1alpha is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis. Am J Physiol Heart Circ Physiol 295: H185-H196, 2008.
41. Leonardsson G, Steel JH, Christian M, Pocock V, Milligan S, Bell J, So PW, Medina-Gomez G, Vidal-Puig A, White R, Parker MG. Nuclear receptor corepressor RIP140 regulates fat accumulation. Proc Natl Acad Sci USA 101: 8437-8442, 2004.
42. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1: 361-370, 2005.
43. Lin J, Tarr PT, Yang R, Rhee J, Puigserver P, Newgard CB, Spiegelman BM. PGC-1beta in the regulation of hepatic glucose and energy metabolism. J Biol Chem 278: 30843-30848, 2003.
44. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S, Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC, Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 119: 121-135, 2004.
45. Lira VA, Benton CR, Yan Z, Bonen A. PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol Endocrinol Metab 299: E145-E161, 2010.
46. Lynch GS, Ryall JG. Role of beta-adrenoceptor signaling in skeletal muscle: implications for muscle wasting and disease. Physiol Rev 88: 729-767, 2008.
47. Miura S, Kai Y, Kamei Y, Ezaki O. Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise. Endocrinology 149: 4527-4533, 2008.
48. Miura S, Kawanaka K, Kai Y, Tamura M, Goto M, Shiuchi T, Minokoshi Y, Ezaki O. An increase in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by beta-adrenergic receptor activation. Endocrinology 148: 3441-3448, 2007.
49. Mounier R, Cavalie H, Lac G, Clottes E. Molecular impact of clenbuterol and isometric strength training on rat EDL muscles. Pflügers Arch 453: 497-507, 2007.
50. Oishi Y, Imoto K, Ogata T, Taniguchi K, Matsumoto H, Fukuoka Y, Roy RR. Calcineurin and heat-shock proteins modulation in clenbuterolinduced hypertrophied rat skeletal muscles. Pflügers Arch 448: 114-122, 2004.
51. Oishi Y, Imoto K, Ogata T, Taniguchi K, Matsumoto H, Roy RR. Clenbuterol induces expression of multiple myosin heavy chain isoforms in rat soleus fibres. Acta Physiol Scand 176: 311-318, 2002.
52. Pan SJ, Hancock J, Ding Z, Fogt D, Lee M, Ivy JL. Effects of clenbuterol on insulin resistance in conscious obese Zucker rats. Am J Physiol Endocrinol Metab 280: E554-E561, 2001.
53. Pellegrino MA, D'Antona G, Bortolotto S, Boschi F, Pastoris O, Bottinelli R, Polla B, Reggiani C. Clenbuterol antagonizes glucocorticoid-induced atrophy and fibre type transformation in mice. Exp Physiol 89: 89-100, 2004.
54. Ricart-Firinga C, Stevens L, Canu MH, Nemirovskaya TL, Mounier Y. Effects of beta(2)-agonist clenbuterol on biochemical and contractile properties of unloaded soleus fibers of rat. Am J Physiol Cell Physiol 278: C582-C588, 2000.
55. Seth A, Steel JH, Nichol D, Pocock V, Kumaran MK, Fritah A, Mobberley M, Ryder TA, Rowlerson A, Scott J, Poutanen M, White R, Parker M. The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle. Cell Metab 6: 236-245, 2007.
56. Shi H, Zeng C, Ricome A, Hannon KM, Grant AL, Gerrard DE. Extracellular signal-regulated kinase pathway is differentially involved in beta-agonist-induced hypertrophy in slow and fast muscles. Am J Physiol Cell Physiol 292: C1681-C1689, 2007.
57. Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci USA 102: 5618-5623, 2005.
58. Soppa GK, Smolenski RT, Latif N, Yuen AH, Malik A, Karbowska J, Kochan Z, Terracciano CM, Yacoub MH. Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle. Am J Physiol Heart Circ Physiol 288: H1468-H1476, 2005.
59. Srere P. Citrate synthase. In: Methods in Enzymology, edited by Lowenstein J. New York: Academic Press, 1969, p. 3-5.
60. Steinberg GR, Dyck DJ, Calles-Escandon J, Tandon NN, Luiken JJ, Glatz JF, Bonen A. Chronic leptin administration decreases fatty acid uptake and fatty acid transporters in rat skeletal muscle. J Biol Chem 277: 8854-8860, 2002.
61. Stevens L, Firinga C, Gohlsch B, Bastide B, Mounier Y, Pette D. Effects of unweighting and clenbuterol on myosin light and heavy chains in fast and slow muscles of rat. Am J Physiol Cell Physiol 279: C1558-C1563, 2000.
62. Sundal S, Sharma S. Ultrastructural findings for the mitochondrial subpopulation of mice skeletal muscle after adrenergic stimulation by clenbuterol. J Physiol Sci 57: 7-14, 2007.
63. Terada S, Tabata I. Effects of acute bouts of running and swimming exercise on PGC-1alpha protein expression in rat epitrochlearis and soleus muscle. Am J Physiol Endocrinol Metab 286: E208-E216, 2004.
64. Torgan CE, Brozinick JT Jr, Banks EA, Cortez MY, Wilcox RE, and Ivy JL. Exercise training and clenbuterol reduce insulin resistance of obese Zucker rats. Am J Physiol Endocrinol Metab 264: E373-E379, 1993.
65. Torgan CE, Etgen GJ Jr, Brozinick JT Jr, Wilcox RE, Ivy JL. Interaction of aerobic exercise training and clenbuterol: effects on insulinresistant muscle. J Appl Physiol 75: 1471-1476, 1993.
66. Torgan CE, Etgen GJ Jr, Kang HY, Ivy JL. Fiber type-specific effects of clenbuterol and exercise training on insulin-resistant muscle. J Appl Physiol 79: 163-167, 1995.
67. Wilson MC, Jackson VN, Heddle C, Price NT, Pilegaard H, Juel C, Bonen A, Montgomery I, Hutter OF, Halestrap AP. Lactic acid efflux from white skeletal muscle is catalyzed by the monocarboxylate transporter isoform MCT3. J Biol Chem 273: 15920-15926, 1998.
68. Yajid F, Mercier JG, Mercier BM, Dubouchaud H, Prefaut C. Effects of 4 wk of hindlimb suspension on skeletal muscle mitochondrial respiration in rats. J Appl Physiol 84: 479-485, 1998.
69. Yoshida Y, Bonen A. Electrotransfection of RIP140 into rat soleus muscle increases its glycolytic profile while reducing its oxidative profile and fatty acid metabolism. Appl Physiol Nutr Metab 34: 1165, 2009.
70. Yoshida Y, Holloway GP, Ljubicic V, Hatta H, Spriet LL, Hood DA, Bonen A. Negligible direct lactate oxidation in subsarcolemmal and intermyofibrillar mitochondria obtained from red and white rat skeletal muscle. J Physiol 582: 1317-1335, 2007.