PGC-1α's relationship with skeletal muscle palmitate oxidation is not present with obesity despite maintained PGC-1α and PGC-1β protein

American Journal of Physiology - Endocrinology and Metabolism

Volumn 294, Issue 6, 2008, Pages

  Holloway, Graham P ^a   Perry, Christopher G R ^a   Thrush, A Brianne ^a   Heigenhauser, George J F ^b   Dyck, David J ^a   Bonen, Arend ^a   Spriet, Lawrence L ^a  

^a UNIVERSITY OF GUELPH   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

Author keywords

Fatty acid oxidation; Mitochondria; Mitochondrial fusion fission; Transcription factors

Indexed keywords

CITRATE SYNTHASE; CYTOCHROME C OXIDASE; MITOFUSIN 1; MITOFUSIN 2; PALMITIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1BETA; CARRIER PROTEIN; DNA BINDING PROTEIN; DNM1L PROTEIN, HUMAN; GUANOSINE TRIPHOSPHATASE; HEAT SHOCK PROTEIN; MEMBRANE PROTEIN; MFN1 PROTEIN, HUMAN; MFN2 PROTEIN, HUMAN; MICROTUBULE ASSOCIATED PROTEIN; MITOCHONDRIAL PROTEIN; PALMITIC ACID DERIVATIVE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PPARGC1A PROTEIN, HUMAN; TFAM PROTEIN, HUMAN; TRANSCRIPTION FACTOR;

ADULT; ARTICLE; BODY MASS; CONTROLLED STUDY; FATTY ACID OXIDATION; FEMALE; HUMAN; HUMAN EXPERIMENT; INSULIN RESISTANCE; MUSCLE METABOLISM; MUSCLE MITOCHONDRION; NORMAL HUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; METABOLISM; MIDDLE AGED; REGRESSION ANALYSIS; SKELETAL MUSCLE; WESTERN BLOTTING;

BLOTTING, WESTERN; CITRATE (SI)-SYNTHASE; DNA-BINDING PROTEINS; FEMALE; GTP PHOSPHOHYDROLASES; HEAT-SHOCK PROTEINS; HUMANS; MEMBRANE PROTEINS; MEMBRANE TRANSPORT PROTEINS; MICROTUBULE-ASSOCIATED PROTEINS; MIDDLE AGED; MITOCHONDRIA, MUSCLE; MITOCHONDRIAL PROTEINS; MUSCLE, SKELETAL; OBESITY; PALMITATES; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; REGRESSION ANALYSIS; TRANSCRIPTION FACTORS;

EID: 47549098993     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00726.2007     Document Type: Article

References (50)

1. Andersen G, Wegner L, Yanagisawa K, Rose CS, Lin J, Glumer C, Drivsholm T, Borch-Johnsen K, Jorgensen T, Hansen T, Spiegelman BM, Pedersen O. Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity. J Med Genet 42: 402-407, 2005.
2. Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, Spiegelman BM. The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle. Cell Metab 5: 35-46, 2007.
3. Bach D, Naon D, Pich S, Soriano FX, Vega N, Rieusset J, Laville M, Guillet C, Boirie Y, Wallberg-Henriksson H, Manco M, Calvani M, Castagneto M, Palacin M, Mingrone G, Zierath JR, Vidal H, Zorzano A. Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6. Diabetes 54: 2685-2693, 2005.
4. Bach D, Pich S, Soriano FX, Vega N, Baumgartner B, Oriola J, Daugaard JR, Lloberas J, Camps M, Zierath JR, Rabasa-Lhoret R, Wallberg-Henriksson H, Laville M, Palacin M, Vidal H, Rivera F, Brand M, Zorzano A. Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem 278: 17190-17197, 2003.
5. Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM. Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes 55: 2277-2285, 2006.
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 SS, not IMF, mitochondria. J Biol Chem 283: 4228-4240, 2008.
7. Bonen A, Parolin ML, Steinberg GR, Calles-Escandon J, Tandon NN, Glatz JF, Luiken JJ, Heigenhauser GJ, Dyck DJ. Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36. FASEB J 18: 1144-1146, 2004.
8. Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsoe R, Dela F. Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50: 790-796, 2007.
9. Cecil JE, Watt P, Palmer CN, Hetherington M. Energy balance and food intake: the role of PPARgamma gene polymorphisms. Physiol Behav 88: 227-233, 2006.
10. De Filippis E, Alvarez G, Berria R, Cusi K, Everman S, Meyer C, Mandarino LJ. Insulin-resistant muscle is exercise resistant: evidence for reduced response of nuclear-encoded mitochondrial genes to exercise. Am J Physiol Endocrinol Metab 294: E607-E614, 2008.
11. Fan M, Rhee J, St-Pierre J, Handschin C, Puigserver P, Lin J, Jaeger S, Erdjument-Bromage H, Tempst P, Spiegelman BM. Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK. Genes Dev 18: 278-289, 2004.
12. Garcia-Roves P, Huss JM, Han DH, Hancock CR, Iglesias-Gutierrez E, Chen M, Holloszy JO. Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle. Proc Natl Acad Sci USA 104: 10709-10713, 2007.
13. Gleyzer N, Vercauteren K, Scarpulla RC. Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol 25: 1354-1366, 2005.
14. Holloway GP, Thrush AB, Heigenhauser GJ, Tandon NN, Dyck DJ, Bonen A, Spriet LL. Skeletal muscle mitochondrial FAT/CD36 content and palmitate oxidation are not decreased in obese women. Am J Physiol Endocrinol Metab 292: E1782-E1789, 2007.
15. Hostetler HA, Kier AB, Schroeder F. Very-long-chain and branched-chain fatty acyl-CoAs are high affinity ligands for the peroxisome proliferator-activated receptor alpha (PPARalpha). Biochemistry 45: 7669-7681, 2006.
16. Jäger S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104: 12017-12022, 2007.
17. Johannsson E, McCullagh KJ, Han XX, Fernando PK, Jensen J, Dahl HA, Bonen A. Effect of overexpressing GLUT-1 and GLUT-4 on insulin-and contraction-stimulated glucose transport in muscle. Am J Physiol Endocrinol Metab 271: E547-E555, 1996.
18. Kamei Y, Ohizumi H, Fujitani Y, Nemoto T, Tanaka T, Takahashi N, Kawada T, Miyoshi M, Ezaki O, Kakizuka A. PPARgamma coactivator 1beta/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. Proc Natl Acad Sci USA 100: 12378-12383, 2003.
19. Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51: 2944-2950, 2002.
20. Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18: 357-368, 2004.
21. Kim JY, Hickner RC, Cortright RL, Dohm GL, Houmard JA. Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab 279: E1039-E1044, 2000.
22. Koves TR, Li P, An J, Akimoto T, Slentz D, Ilkayeva O, Dohm GL, Yan Z, Newgard CB, Muoio DM. Peroxisome proliferator-activated receptor-gamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem 280: 33588-33598, 2005.
23. Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106: 847-856, 2000.
24. Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M, Wozniak DF, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy JO, Medeiros DM, Schmidt RE, Saffitz JE, Abel ED, Semenkovich CF, Kelly DP. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol 3: e101, 2005.
25. Li X, Monks B, Ge Q, Birnbaum MJ. Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature 447: 1012-1016, 2007.
26. 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.
27. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jäger 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.
28. Miura S, Kai Y, Ono M, Ezaki O. Overexpression of peroxisome proliferator-activated receptor gamma coactivator-1alpha down-regulates GLUT4 mRNA in skeletal muscles. J Biol Chem 278: 31385-31390, 2003.
29. Mogensen M, Sahlin K, Fernstrom M, Glintborg D, Vind BF, Beck-Nielsen H, Hojlund K. Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 56: 1592-1599, 2007.
30. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34: 267-273, 2003.
31. Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 115: 3587-3593, 2005.
32. Muoio DM, Way JM, Tanner CJ, Winegar DA, Kliewer SA, Houmard JA, Kraus WE, Dohm GL. Peroxisome proliferator-activated receptor-alpha regulates fatty acid utilization in primary human skeletal muscle cells. Diabetes 51: 901-909, 2002.
33. Ort T, Gerwien R, Lindborg KA, Diehl CJ, Lemieux AM, Eisen A, Henriksen EJ. Alterations in soleus muscle gene expression associated with a metabolic endpoint following exercise training by lean and obese Zucker rats. Physiol Genomics 29: 302-311, 2007.
34. 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 PGC-1 and NRF1. Proc Natl Acad Sci USA 100: 8466-8471, 2003.
35. Pich S, Bach D, Briones P, Liesa M, Camps M, Testar X, Palacin M, Zorzano A. The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet 14: 1405-1415, 2005.
36. Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM. Activation of PPARgamma coactivator-1 through transcription factor docking. Science 286: 1368-1371, 1999.
37. Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang CY, Krauss S, Mootha VK, Lowell BB, Spiegelman BM. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Mol Cell 8: 971-982, 2001.
38. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92: 829-839, 1998.
39. Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, Kelley DE. Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes 54: 8-14, 2005.
40. Scarpulla RC. Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta 1576: 1-14, 2002.
41. Smirnova E, Griparic L, Shurland DL, van der Bliek AM. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 12: 2245-2256, 2001.
42. Sookoian S, Garcia SI, Porto PI, Dieuzeide G, Gonzalez CD, Pirola CJ. Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents. J Mol Endocrinol 35: 373-380, 2005.
43. Stojanovski D, Koutsopoulos OS, Okamoto K, Ryan MT. Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology. J Cell Sci 117: 1201-1210, 2004.
44. Tanaka T, Yamamoto J, Iwasaki S, Asaba H, Hamura H, Ikeda Y, Watanabe M, Magoori K, Ioka RX, Tachibana K, Watanabe Y, Uchiyama Y, Sumi K, Iguchi H, Ito S, Doi T, Hamakubo T, Naito M, Auwerx J, Yanagisawa M, Kodama T, Sakai J. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome. Proc Natl Acad Sci USA 100: 15924-15929, 2003.
45. Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 144: 5159-5165, 2003.
46. Vianna CR, Huntgeburth M, Coppari R, Choi CS, Lin J, Krauss S, Barbatelli G, Tzameli I, Kim YB, Cinti S, Shulman GI, Spiegelman BM, Lowell BB. Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance. Cell Metab 4: 453-464, 2006.
47. Watt MJ, Southgate RJ, Holmes AG, Febbraio MA. Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) alpha and delta and PPAR coactivator 1alpha in human skeletal muscle, but not lipid regulatory genes. J Mol Endocrinol 33: 533-544, 2004.
48. Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem 282: 194-199, 2007.
49. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98: 115-124, 1999.
50. Zorzano A, Pich S. What is the biological significance of the two mitofusin proteins present in the outer mitochondrial membrane of mammalian cells? IUBMB Life 58: 441-443, 2006.