Updating the effects of fatty acids on skeletal muscle

Journal of Cellular Physiology

Volumn 217, Issue 1, 2008, Pages 1-12

  Silveira, Leonardo R ^a   Fiamoncini, Jarlei ^a   Hirabara, Sandro M ^b   Procópio, Joaquim ^a   Cambiaghi, Tavane D ^a   Pinheiro, Carlos Hermano J ^a   Lopes, Lúcia R ^a   Curi, Rui ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b UNIVERSIDADE CRUZEIRO DO SUL   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

CERAMIDE; COENZYME A; DIACYLGLYCEROL; FATTY ACID; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN RECEPTOR SUBSTRATE 1; INSULIN RECEPTOR SUBSTRATE 2; LONG CHAIN ACYL COENZYME A; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE C; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; CITRIC ACID CYCLE; DYSLIPIDEMIA; FATTY ACID METABOLISM; FATTY ACID OXIDATION; FATTY ACID SYNTHESIS; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GLUCOSE OXIDATION; HUMAN; INFLAMMATION; INSULIN METABOLISM; INSULIN RESISTANCE; INSULIN RESPONSE; LIPID DIET; LIPOLYSIS; MUSCLE CELL; MUSCLE METABOLISM; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; ANIMAL; METABOLISM; PHYSIOLOGY;

ANIMALS; FATTY ACIDS; HUMANS; INSULIN RESISTANCE; MUSCLE, SKELETAL; OXIDATIVE STRESS;

EID: 49649090886     PISSN: 00219541     EISSN: None     Source Type: Journal    
DOI: 10.1002/jcp.21514     Document Type: Review

References (104)

1. Akira S, Sato S. 2003. Toll-like receptors and their signaling mechanisms. Scand J Infect Dis 35:555-562.
2. Alberici LC, Oliveira HC, Bighetti EJ, de Faria EC, Degaspari GR, Souza CT, Vercesi AE. 2003. Hypertriglyceridemia increases mitochondrial resting respiration and susceptibility to permeability transition. J Bioenerg Biomembr 35:451-457.
3. Alberici LC, Oliveira HC, Patricio PR, Kowaltowski AJ, Vercesi AE. 2006. Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K+ channel activity. Gastroenterology 131:1228-1234.
4. Andersson U, Leighton B, Young ME, Blomstrand E, Newsholme EA. 1998. Inactivation of aconitase and oxoglutarate dehydrogenase in skeletal muscle in vitro by superoxide anions and/or nitric oxide. Biochem Biophys Res Commun 249:512-516.
5. Arkinstall MJ, Tunstall RJ, Cameron-Smith D, Hawley JA. 2004. Regulation of metabolic genes in human skeletal muscle by short-term exercise and diet manipulation. Am J Physiol Endocrinol Metab 287:E25-E31.
6. Bernardi P, Penzo D, Wojtczak L. 2002. Mitochondrial energy dissipation by fatty acids. Mechanisms and implications for cell death. Vitam Horm 65:97-126.
7. Black PN, Faergeman NJ, DiRusso CC. 2000. Long-chain acyl-CoA-dependent regulation of gene expression in bacteria, yeast and mammals. J Nutr 130:305S-309S.
8. Boden G, Chen X. 1995. Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes. J Clin Invest 96:1261-1268.
9. Brunaldi K, Miranda MA, Abdulkader F, Curi R, Procopio J. 2004. Effects of palmitic acid and cholesterol on proton transport across black lipid membranes. Bioelectrochem 65:9-13.
10. Cabrero A, Alegret M, Sanchez RM, Adzet T, Laguna JC, Carrera MV. 2002. Increased reactive oxygen species production down-regulates peroxisome proliferator-activated alpha pathway in C2C12 skeletal muscle cells. J Biol Chem 277:10100-10107.
11. Cameron-Smith D, Burke LM, Angus DJ, Tunstall RJ, Cox GR, Bonen A, Hawley JA, Hargreaves MA. 2003. Short-term, high-fat diet up-regulates lipid metabolism and gene expression in human skeletal muscle. Am J Clin Nutr 77:313-318.
12. Cha BS, Ciaraldi TP, Carter L, Nikoulina SE, Mudaliar S, Mukherjee R, Paterniti JR Jr, Henry RR. 2001. Peroxisome proliferator-activated receptor (PPAR) gamma and retinoid X receptor (RXR) agonists have complementary effects on glucose and lipid metabolism in human skeletal muscle. Diabetologia 44:444-452.
13. Chevillotte E, Rieusset J, Roques M, Desage M, Vidal H. 2001. The regulation of uncoupling protein-2 gene expression by omega-6 polyunsaturated fatty acids in human skeletal muscle cells involves multiple pathways, including the nuclear receptor peroxisome proliferator-activated receptor beta. J Biol Chem 276:10853-10860.
14. Christon R, Drouin O, Marette A. 2005. Redox modulation of insulin signalingand endothelial function. Antioxid Redox Signal 7:1062-1070.
15. Civitarese AE, Hesselink MK, Russell AP, Ravussin E, Schrauwen P. 2005. Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes. Am J Physiol Endocrinol Metab 289:E1023-E1029.
16. Coyle EF. 1999. Fat oxidation during exercise: Role of lipolysis, FFA availability, and glycolytic flux. In: Hargreaves XM, Thompson M, editors. Biochemistry of exercise X. Champaign, IL: Human Kinetics. pp 263-273.
17. Coyle EF, Jeukendrup AE, Wagenmakers AJM, Saris WHM. 1997. Fatty acid oxidation is directly regulated by carbohydrate metabolim during exercise. Am J Physiol Endocrinol Metab 273:E268-E275.
18. Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, Shulman GI. 1999. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 103:253-259.
19. Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD. 2002. Superoxide activates mitochondrial uncoupling proteins. Nature 415:96-99.
20. Eckel J, Asskamp B, Reinauer H. 1991. Induction of insulin resistance in primary cultured adult cardiac myocytes. Endocrinology 129:345-352.
21. Fabris R, Nisoli E, Lombardi AM, Tonello C, Serra R, Granzotto M, Cusin I, Rohner-Jeanrenaud F, Federspil G, Carruba MO, Vettor R. 2001. Preferential channeling of energy fuels toward fat rather than muscle during high free fatty acid availability in rats. Diabetes 50:601-608.
22. Gardner PR, Fridovich I. 1992. Inactivation-reactivation of aconitase in Escherichia coli. J Biol Chem 13:8757-8763.
23. Gilde AJ, Van Bilsen M. 2003. Peroxisome proliferator-activated receptors (PPARS): Regulators of gene expression in heart and skeletal muscle. Acta Physiol Scand 178:425-434.
24. Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI. 1999. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signalingcascade. Diabetes 48:1270-1274.
25. Hajduch E, Balendran A, Batty IH, Litherland GJ, Blair AS, Downes CP, Hundal HS. 2001. Ceramide impairs the insulin-dependent membrane recruitment of protein kinase B leading to a loss in downstream signalling in L6 skeletal muscle cells. Diabetologia 44:173-183.
26. Hansson O, Donsmark M, Ling C, Nevsten P, Danfelter M, Andersen JL, Galbo H, Holm C. 2005. Transcriptome and proteome analysis of soleus muscle of hormone-sensitive lipase-null mice. J Lipid Res 46:2614-2623.
27. Harper JA, Stuart JA, Jekabsons MB, Roussel D, Brindle KM, Dickinson K, Jones RB, Brand MD. 2002. Artifactual uncoupling by uncoupling protein 3 in yeast mitochondria at the concentrations found in mouse and rat skeletal-muscle mitochondria. Biochem J 361:49-56.
28. Hatanaka E, Levada-Pires AC, Pithon-Curi TC, Curi R. 2006. Systematic study on ROS production induced by oleic, linoleic, and gamma-linolenic acids in human and rat neutrophils. Free Radic Biol Med 41:1124-1132.
29. Hawley JA. 1994. Nutritional strategies to enhance fat oxidation during aerobic exercise. In: Burke L, Deakin V, editors. Clinical sports nutrition. Sydney, Australia: McGraw-Hill. pp 428-454.
30. Hawley JA, Burke LM, Angus DJ, Fallon KE, Martin DT, Febbraio MA. 2000. Effect of altering substrate availability on metabolism and performance during intense exercise. Br J Nutr 84:829-838.
31. Hawley JA, Hargreaves M, Zierath JR. 2006. Signalling mechanisms in skeletal muscle: Role in substrate selection and muscle adaptation. Essays Biochem 42:1-12.
32. Hirabara SM, Silveira LR, Abdulkader F, Carvalho CR, Procopio J, Curi R. 2007. Time-dependent effects of fatty acids on skeletal muscle metabolism. J Cell Physiol 210:7-15.
33. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. 2002. A central role for JNK in obesity and insulin resistance. Nature 420:333-336.
34. Houstis N, Rosen ED, Lander ES. 2006. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944-948.
35. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. 2000. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49:1939-1945.
36. Itani SI, Ruderman NB, Schmieder F, Boden G. 2002. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 51:2005-2011.
37. Jarmuszkiewicz W, Navet R, Alberici LC, Douette P, Sluse-Goffart CM, Sluse FE, Vercesi EA. 2004. Redox state of endogenous coenzyme Q modulates the inhibition of linoleic acid-induced uncoupling by guanosine triphosphate in isolated skeletal muscle mitochondria. J Bioenerg Biomembr 36:493-502.
38. Jenkins AB, Storlien LH, Chisholm DJ, Kraegen EW. 1998. Effects of nonesterified fatty acid availability on tissue-specific glucose utilization in rats in vivo. J Clin Invest 82:293-299.
39. Johnson AB, Argyraki M, Thow JC, Cooper BG, Fulcher G, Taylor R. 1992. Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man. Clin Sci 82:219-226.
40. Kadenbach B. 2003. Intrinsic and extrinsic uncoupling of oxidative phosphorylation. Biochim Biophys Acta 1604:77-94.
41. Kamp F, Zakim D, Zhang F, Noy N, Hamilton JA. 1995. Fatty acid flip-flop in phospholipid bylayers is extremely fast. Biochemistry 34:11928-11937.
42. Kelley DE, Mandarino LJ. 2000. Fuel selection in human skeletal muscle in insulin resistance: A reexamination. Diabetes 49:677-683.
43. Kiens B, Roeman THM, Van der Vusse GJ. 1999. Muscular long-chain fatty acid content during graded exercise in humans. Am J Physiol Endocrinol Metab 276:E352-E357.
44. Kim JK. 2006. Fat uses a TOLL-road to connect inflammation and diabetes. Cell Metab 4:417-419.
45. Lawrence L, Dyck DJ. 1994. The glucose-fatty acid cycle in skeletal muscle at rest and during exercise. In: Maughan RJ, Shirreffs SM, editors. Biochemistry of exercise IX. Champaign, IL: Human Kinetics. pp 127-155.
46. Mattern HM, Hardin CD. 2007. Vascular metabolic dysfunction and lipotoxicity. Physiol Res 56:149-158.
47. McFarlin BK, Flynn MG, Campbell WW, Craig BA, Robinson JP, Stewart LK, Timmerman KL, Coen PM. 2006. Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. J Gerontol A Biol Sci Med Sci 61:388-393.
48. 2+-activated mitochondrial pores. J Bioenerg Biomembr 33:319-331.
49. 2+ cycle mediated by the palmitate-activated cyclosporin A-insensitive pore. J Bioenerg Biomembr 39:167-174.
50. Mitchell P. 1961. Coupling of phosphorylation to electron and hydrogen transfer by a chemiosmotic type of mechanism. Nature 191:144-148.
51. Miyata KS, McCaw SE, Meertens LM, Patel HV, Rachubinski RA, Capone JP. 1998. Receptor-interacting protein 140 interacts with and inhibits trans activation by, peroxisome proliferator-activated receptor alpha and liver-X-receptor alpha. Mol Cell Endocrinol 146:69-76.
52. Muoio DM, MacLean PS, Lang DB, Li S, Houmard JA, Way JM, Winegar DA, Corton JC, Dohm GL, Kraus WE. 2002. Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) alpha knock-out mice. Evidence for compensatory regulation by PPAR delta. J Biol Chem 277:26089-26097.
53. Newsholme EA, Start C. 1973. Adipose tissue and the regulation of fat Metabolism. In: Regulation in metabolism. Oxford, England: John Wiley & Sons. pp 195-243.
54. Pégorier JP, Le May C, Girard J. 2004. Control of gene expression by fatty acids. J Nutr 134:2444S-2449S.
55. Penzo D, Tagliapietra C, Colonna R, Petronilli V, Bernardi P. 2002. Effects of fatty acids on mitochondria: Implications for cell death. Biochim Biophys Acta 1555:160-165.
56. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. 2004. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664-671.
57. Piatti PM, Monti LD, Davis SN, Conti M, Brown MD, Pozza G, Alberti KG. 1996. Effects of an acute decrease in non-esterified fatty acid levels on muscle glucose utilization and forearm indirect calorimetry in lean NIDDM patients. Diabetologia 39:103-112.
58. Pilegaard H, Ordway GA, Saltin B, Neufer PD. 2000. Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise. Am J Physiol Endocrinol Metab 279:E806-E814.
59. Powell DJ, Turban S, Gray A, Hajduch E, Hundal HS. 2004. Intracellular ceramide synthesis and protein kinase Czeta activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells. Biochem J 382:619-629.
60. Rachek LI, Musiyenko SI, LeDoux SP, Wilson GL. 2007. Palmitate induced mitochondrial deoxyribonucleic acid damage and apoptosis in L6 rat skeletal muscle cells. Endocrinology 148:293-299.
61. Randle PJ. 1998. Regulatory interactions between lipids and carbohydrates: The glucose fatty acid cycle after 35 years. Diabetes Metab Rev 14:263-283.
62. Randle PJ, Garland PB, Hales CN, Newsholme EA. 1963. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1 13:78S-789.
63. Richardson DK, Kashyap S, Bajaj M, Cusi K, Mandarino SJ, Finlayson J, DeFronzo RA, Jenkinson CP, Mandarino LJ. 2005. Lipid infusion decreases the expression of nuclear encoded mitochondrial genes and increases the expression of extracellular matrix genes in human skeletal muscle. J Biol Chem 280:10290-10297.
64. Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, Shulman GI. 1996. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 97:2859-2865.
65. Rolo AP, Palmeira CM. 2006. Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 212:167-178.
66. Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E, Wolfe RR. 1993. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol Endocrinol Metab 265:E380-E391.
67. Ruderman NB, Saha AK, Vavas D, Witters LA. 1999. Malonyl-CoA, fuel sensing, and insulin resistance. Am J Physiol 276:E1-E18.
68. Russell AP. 2004. Lipotoxicity: The obese and endurance-trained paradox. Int J Obes Relat Metab Disord 28:S66-S71.
69. Sahlin K, Katz A, Broberg S. 1990. Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise. Am J Physol Cell Physiol 259:C834-C841.
70. Sampath H, Ntambi JM. 2005. Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu Rev Nutr 2S:317-340.
71. Savage DB, Petersen KF, Shulman GI. 2007. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 87:507-520.
72. Schmid GM, Converset V, Walter N, Sennitt MV, Leung KY, Byers H, Ward M, Hochstrasser DF, Cawthorne MA, Sanchez JC. 2004. Effect of high-fat diet on the expression of proteins in muscle, adipose tissues, and liver of C57BL/6 mice. Proteomics 4:2270-2282.
73. Schonfeld P, Schlüter T, Schüttig R, Bohnensack R. 2001. Activation of ion-conducting pathways in the inner mitochondrial membrane - An unrecognized activity of fatty acid? FEBS Lett 491:45-49.
74. Schonfeld P, Gerke S, Bohnensack R, Wojtczak L. 2003. Stimulation of potassium cycling in mitochondria by long-chain fatty acids. Biochim Biophys Acta 1604:125-133.
75. Schrauwen P, Hesselink MK. 2001. An alternative function for human uncoupling protein 3: Protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix. FASEB J 15:2497-2502.
76. Schrauwen P, Hoeks J, Schaart G, Kornips E, Binas B, Van De Vusse GJ, Van Bilsen M, Luiken JJ, Coort SL, Glatz JF, Saris WH, Hesselink MK. 2003. Uncoupling protein 3 as a mitochondrial fatty acid anion exporter. FASEB J 17:2272-2274.
77. Senn JJ. 2006. Toll-like receptor-2 is essential for the development of palmitate-induced insulin resistance in myotubes. J Biol Chem 281:26865-26875.
78. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. 2006. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116:3015-3025.
79. Silveira LR, Pereira-da-Silva L, Juel C, Hellsten Y. 2003. Formation of hydrogen peroxide and nitric oxide in rat skeletal muscle cells during contactions. Free Rad Biol Med 35:455-464.
80. Silveira LR, Pilegaard H, Kushuara K, Curi R, Hellsten Y. 2006. The contraction induced increase in gene expression of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator I -alpha (PGC-1α), mitochondrial uncoupling protein 3 (UCP3) and hexokinase II (HKII) in primary rat skeletal muscle cells is dependent on reactive oxygen species. Biochim Biophys Acta 1763:969-976.
81. Silveira LR, Hirabara SM, Alberici LC, Lambertucci RH, Peres CM, Takahashi HK, Pettri A, Alba-Loureiro T, Luchessi AD, Cury-Boaventura MF, Vercesi AE, Curi R. 2007. Effect of lipid infusion on metabolism and force of rat skeletal muscles during intense contractions. Cell Physiol Biochem 20:213-226.
82. Skulachev VP. 1998. Uncoupling: New approaches to an old problem of bioenergetics. Biochim Biophys Acta 1363:100-124.
83. Sparks LM, Xie H, Koza RA, Mynatt R, Hulver MW, Bray GA, Smith SR. 2005. A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Diabetes 54:1926-1933.
84. Spriet LL. 2002. Regulation of skeletal muscle fat oxidation during exercise in humans. Med Sci Sports Exer 34:1477-1484.
85. Sugden MC. 2007. In appreciation of Sir Philip Randle: The glucose-fatty acid cycle. Br J Nutr 97:809-813.
86. Sultan A, Sokolove PM. 2001. Palmitic acid opens a novel cyclosporin A-insensitive pore in the inner mitochondrial membrane. Arch Biochem Biophys 86:37-51.
87. Summers SA, Garza LA, Zhou H, Birnbaum MJ. 1998. Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide. Mol Cell Biol 18:5457-5464.
88. Takeda K, Akira S. 2001. Regulation of innate immune responses by Toll-like receptors. Jpn J Infect Dis 54:209-219.
89. Talbot DA, Brand MD. 2005. Uncoupling protein 3 protects aconitase against inactivation in isolated skeletal muscle mitochondria. Biochim Biophys Acta 1709:150-156.
90. Talbot DA, Lambert AJ, Brand MD. 2004. Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3. FEBS Lett 556:111-115.
91. Tremblay F, Brule S, Hee Um S, Li Y, Masuda K, Roden M, Sun XJ, Krebs M, Polakiewicz RD, Thomas G, Marette A. 2007. Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient-and obesity-induced insulin resistance. Proc Natl Acad Sci USA 104:14056-14061.
92. Tretter L, Adam-vizi V. 2000. Inhibition of Krebs cycle enzymes by hydrogen peroxide: A key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. J Neurosci 20:8972-8979.
93. Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, Araújo EP, Vassallo J, Curi R, Velloso LA, Saad MJ. 2007. Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56:1986-1988.
94. Tunstall RJ, Cameron-Smith D. 2005. Effect of elevated lipid concentrations on human skeletal muscle gene expression. Metabolism 54:952-959.
95. Tunstall RJ, Mehan KA, Hargreaves M, Spriet LL, Cameron-Smith D. 2002. Fasting activates the gene expression of UCP3 independent of genes necessary for lipid transport and oxidation in skeletal muscle. Biochem Biophys Res Commun 294:301-308.
96. Tunstall RJ, McAinch AJ, Hargreaves M, van Loon LJ, Cameron-Smith D. 2007. Reduced plasma free fatty acid availability during exercise: Effect on gene expression. Eur J Appl Physiol 99:485-493.
97. Turpin SM, Lancaster GI, Darby I, Febbraio MA, Watt MJ. 2006. Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance. Am J Physiol Endocrinol Metab 291:E1341-E1350.
98. Ueno M, Carvalheira JB, Tambascia RC, Bezerra RM, Amaral ME, Carneiro EM, Folli F, Franchini KG, Saad MJ. 2005. Regulation of insulin signalling by hyperinsulinaemia: Role of IRS-1/2 serine phosphorylation and the mTOR/p70 S6K pathway. Diabetologia 48:506-518.
99. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. 1997. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389:610-614.
100. van Loon LJ, Goodpaster BH. 2006. Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state. Pflugers Arch 451:606-616.
101. Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V, Cortright R, Muoio DM, Lowell BB. 2000. Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem 275:16258-16266.
102. Watanabe K, Fujii H, Takahashi T, Kodama M, Aizawa Y, Ohta Y, Ono T, Hasegawa G, Naito M, Nakajima T, Kamijo Y, Gonzalez FJ, Aoyama T. 2000. Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age-dependent cardiac toxicity. J Biol Chem 275:22293-22299.
103. Willis WT, Jackman MR. 1994. Mitochondrial function during heavy exercise. Med Sci Sports Exerc 26:1347-1353.
104. Young ME, Guthrie PH, Razeghi P, Leighton B, Abbasi S, Patil S, Youker KA, Taegtmeyer H. 2002. Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes 51:2587-2595.