1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Nutrition
  4. Volume 30, 2010
  5. Article

Annual Review of Nutrition

Volume 30, 2010

The Effect of Exercise and Nutrition on Intramuscular Fat Metabolism and Insulin Sensitivity

Abstract

Intramuscular triacylglycerol (IMTG) is both a dynamic fat-storage depot that can expand during periods of elevated lipid availability and a fatty acid source that can be utilized during periods of increased energy expenditure in active individuals. Although many studies have investigated the lifestyle determinants of IMTG content, the results are far from consistent, and studies attempting to unravel the mechanisms behind IMTG metabolism are in their infancy. The limited evidence available suggests that the enzymes responsible for skeletal muscle lipolysis and IMTG synthesis play an important role in determining the fate of fatty acids and therefore the concentration of lipid metabolites and insulin sensitivity of skeletal muscle. This review provides a summary of current knowledge on the effects of acute and chronic exercise as well as energy intake and macronutrient composition of the diet upon the metabolism of IMTG and the implications for metabolic health.

Keyword(s): diet, intramuscular triglyceride (IMTG), intramyocellular lipid (IMCL), lipolysis, skeletal muscle, triglyceride synthesis
Loading

Article metrics loading...

/content/journals/10.1146/annurev.nutr.012809.104817
2010-08-21
2025-03-24
Loading full text...

Full text loading...

/deliver/fulltext/nutr/30/1/annurev.nutr.012809.104817.html?itemId=/content/journals/10.1146/annurev.nutr.012809.104817&mimeType=html&fmt=ahah

Literature Cited

  1. Achten J, Gleeson M, Jeukendrup AE. 1.  2002. Determination of the exercise intensity that elicits maximal fat oxidation. Med. Sci. Sports Exerc. 34:92–97 [Google Scholar]
  2. Alsted TJ, Nybo L, Schweiger M, Fledelius C, Jacobsen P. 2.  et al. 2009. Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training. Am. J. Physiol. Endocrinol. Metab. 296:E445–53 [Google Scholar]
  3. Bachmann OP, Dahl DB, Brechtel K, Machann J, Haap M. 3.  et al. 2001. Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans. Diabetes 50:2579–84 [Google Scholar]
  4. Bergman BC, Butterfield GE, Wolfel EE, Casazza GA, Lopaschuk GD, Brooks GA. 4.  1999. Evaluation of exercise and training on muscle lipid metabolism. Am. J. Physiol. 276:E106–17 [Google Scholar]
  5. Bergstrom J, Hermansen L, Hultman E, Saltin B. 5.  1967. Diet, muscle glycogen and physical performance. Acta Physiol. Scand. 71:140–50 [Google Scholar]
  6. Blaak EE, Schiffelers SL, Saris WH, Mensink M, Kooi ME. 6.  2004. Impaired beta-adrenergically mediated lipolysis in skeletal muscle of obese subjects. Diabetologia 47:1462–68 [Google Scholar]
  7. Blaak EE, van Aggel-Leijssen DP, Wagenmakers AJ, Saris WH, van Baak MA. 7.  2000. Impaired oxidation of plasma-derived fatty acids in type 2 diabetic subjects during moderate-intensity exercise. Diabetes 49:2102–7 [Google Scholar]
  8. Blaak EE, Wagenmakers AJ, Glatz JF, Wolffenbuttel BH, Kemerink GJ. 8.  et al. 2000. Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle. Am. J. Physiol. Endocrinol. Metab. 279:E146–54 [Google Scholar]
  9. Bonen A, Parolin ML, Steinberg GR, Calles-Escandon J, Tandon NN. 9.  et al. 2004. 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. 18:1144–46 [Google Scholar]
  10. Bostrom P, Andersson L, Rutberg M, Perman J, Lidberg U. 10.  et al. 2007. SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity. Nat. Cell Biol. 9:1286–93 [Google Scholar]
  11. Bruce CR, Kriketos AD, Cooney GJ, Hawley JA. 11.  2004. Disassociation of muscle triglyceride content and insulin sensitivity after exercise training in patients with type 2 diabetes. Diabetologia 47:23–30 [Google Scholar]
  12. Bruce CR, Thrush AB, Mertz VA, Bezaire V, Chabowski A. 12.  et al. 2006. Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am. J. Physiol. Endocrinol. Metab. 291:E99–107 [Google Scholar]
  13. Budohoski L, Gorski J, Nazar K, Kaciuba-Uscilko H, Terjung RL. 13.  1996. Triacylglycerol synthesis in the different skeletal muscle fiber sections of the rat. Am. J. Physiol. 271:E574–81 [Google Scholar]
  14. Chalkley SM, Hettiarachchi M, Chisholm DJ, Kraegen EW. 14.  1998. Five-hour fatty acid elevation increases muscle lipids and impairs glycogen synthesis in the rat. Metabolism 47:1121–26 [Google Scholar]
  15. Chanarin I, Patel A, Slavin G, Wills EJ, Andrews TM, Stewart G. 15.  1975. Neutral-lipid storage disease: a new disorder of lipid metabolism. Br. Med. J. 1:553–55 [Google Scholar]
  16. Chatzinikolaou A, Fatouros I, Petridou A, Jamurtas A, Avloniti A. 16.  et al. 2008. Adipose tissue lipolysis is upregulated in lean and obese men during acute resistance exercise. Diabetes Care 31:1397–99 [Google Scholar]
  17. Chavez JA, Summers SA. 17.  2003. Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes. Arch. Biochem. Biophys. 419:101–9 [Google Scholar]
  18. Coggan AR, Coyle EF. 18.  1989. Metabolism and performance following carbohydrate ingestion late in exercise. Med. Sci. Sports Exerc. 21:59–65 [Google Scholar]
  19. Coggan AR, Raguso CA, Gastaldelli A, Sidossis LS, Yeckel CW. 19.  2000. Fat metabolism during high-intensity exercise in endurance-trained and untrained men. Metabolism 49:122–28 [Google Scholar]
  20. Coleman RA, Lee DP. 20.  2004. Enzymes of triacylglycerol synthesis and their regulation. Prog. Lipid Res. 43:134–76 [Google Scholar]
  21. Coll T, Eyre E, Rodriguez-Calvo R, Palomer X, Sánchez RM. 21.  et al. 2008. Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. J. Biol. Chem. 283:11107–16 [Google Scholar]
  22. Coyle EF, Jeukendrup AE, Wagenmakers AJ, Saris WH. 22.  1997. Fatty acid oxidation is directly regulated by carbohydrate metabolism during exercise. Am. J. Physiol. 273:E268–75 [Google Scholar]
  23. De BK, Dresselaers T, Kiens B, Richter EA, Van HP, Hespel P. 23.  2007. Evaluation of intramyocellular lipid breakdown during exercise by biochemical assay, NMR spectroscopy, and oil red O staining. Am. J. Physiol. Endocrinol. Metab. 293:E428–34 [Google Scholar]
  24. De BK, Richter EA, Russell AP, Eijnde BO, Derave W. 24.  et al. 2005. Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans. J. Physiol. 564:649–60 [Google Scholar]
  25. Decombaz J, Schmitt B, Ith M, Decarli B, Diem P. 25.  et al. 2001. Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects. Am. J. Physiol. Regul. Integr. Comp. Physiol. 281:R760–69 [Google Scholar]
  26. Dube JJ, Amati F, Stefanovic-Racic M, Toledo FG, Sauers SE, Goodpaster BH. 26.  2008. Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited. Am. J. Physiol. Endocrinol. Metab. 294:E882–88 [Google Scholar]
  27. Dyck DJ, Steinberg G, Bonen A. 27.  2001. Insulin increases FA uptake and esterification but reduces lipid utilization in isolated contracting muscle. Am. J. Physiol. Endocrinol. Metab. 281:E600–7 [Google Scholar]
  28. Egan JJ, Greenberg AS, Chang MK, Wek SA, Moos MC Jr, Londos C. 28.  1992. Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet. Proc. Natl. Acad. Sci. USA 89:8537–41 [Google Scholar]
  29. Ellis BA, Poynten A, Lowy AJ, Furler SM, Chisholm DJ. 29.  et al. 2000. Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle. Am. J. Physiol. Endocrinol. Metab. 279:E554–60 [Google Scholar]
  30. Enevoldsen LH, Stallknecht B, Langfort J, Petersen LN, Holm C. 30.  et al. 2001. The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle. J. Physiol. 536:871–77 [Google Scholar]
  31. Essen-Gustavsson B, Tesch PA. 31.  1990. Glycogen and triglyceride utilization in relation to muscle metabolic characteristics in men performing heavy-resistance exercise. Eur. J. Appl. Physiol. Occup. Physiol. 61:5–10 [Google Scholar]
  32. Fox AK, Kaufman AE, Horowitz JF. 32.  2004. Adding fat calories to meals after exercise does not alter glucose tolerance. J. Appl. Physiol. 97:11–16 [Google Scholar]
  33. Frangioudakis G, Ye JM, Cooney GJ. 33.  2005. Both saturated and n-6 polyunsaturated fat diets reduce phosphorylation of insulin receptor substrate-1 and protein kinase B in muscle during the initial stages of in vivo insulin stimulation. Endocrinology 146:5596–603 [Google Scholar]
  34. Gan SK, Kriketos AD, Ellis BA, Thompson CH, Kraegen EW, Chisholm DJ. 34.  2003. Changes in aerobic capacity and visceral fat but not myocyte lipid levels predict increased insulin action after exercise in overweight and obese men. Diabetes Care 26:1706–13 [Google Scholar]
  35. Giacco R, Clemente G, Busiello L, Lasorella G, Rivieccio AM. 35.  et al. 2004. Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight. Int. J. Obes. Relat. Metab. Disord. 28:342–48 [Google Scholar]
  36. Gonzalez-Baro MR, Lewin TM, Coleman RA. 36.  2007. Regulation of triglyceride metabolism II. Function of mitochondrial GPAT1 in the regulation of triacylglycerol biosynthesis and insulin action. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G1195–99 [Google Scholar]
  37. Goodpaster BH, He J, Watkins S, Kelley DE. 37.  2001. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J. Clin. Endocrinol. Metab. 86:5755–61 [Google Scholar]
  38. Goodpaster BH, Theriault R, Watkins SC, Kelley DE. 38.  2000. Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism 49:467–72 [Google Scholar]
  39. Granneman JG, Moore HP, Krishnamoorthy R, Rathod M. 39.  2009. Perilipin controls lipolysis by regulating the interactions of Ab-hydrolase containing 5 (Abhd5) and adipose trigylceride lipase (ATGL). J. Biol. Chem. 284:34538–44 [Google Scholar]
  40. Greco AV, Mingrone G, Giancaterini A, Manco M, Morroni M. 40.  et al. 2002. Insulin resistance in morbid obesity. Diabetes 51:144–51 [Google Scholar]
  41. Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C. 41.  1991. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets. J. Biol. Chem. 266:11341–46 [Google Scholar]
  42. Haemmerle G, Zimmermann R, Hayn M, Theussl C, Waeg G. 42.  et al. 2002. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J. Biol. Chem. 277:4806–15 [Google Scholar]
  43. Hammond LE, Neschen S, Romanelli AJ, Cline GW, Ilkayeva OR. 43.  et al. 2005. Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs. J. Biol. Chem. 280:25629–36 [Google Scholar]
  44. Harber MP, Crane JD, Douglass MD, Weindel KD, Trappe TA. 44.  et al. 2008. Resistance exercise reduces muscular substrates in women. Int. J. Sports Med. 29:719–25 [Google Scholar]
  45. He J, Goodpaster BH, Kelley DE. 45.  2004. Effects of weight loss and physical activity on muscle lipid content and droplet size. Obes. Res. 12:761–69 [Google Scholar]
  46. Helge JW, Biba TO, Galbo H, Gaster M, Donsmark M. 46.  2006. Muscle triacylglycerol and hormone-sensitive lipase activity in untrained and trained human muscles. Eur. J. Appl. Physiol. 97:566–72 [Google Scholar]
  47. Helge JW, Dela F. 47.  2003. Effect of training on muscle triacylglycerol and structural lipids: a relation to insulin sensitivity?. Diabetes 52:1881–87 [Google Scholar]
  48. Helge JW, Watt PW, Richter EA, Rennie MJ, Kiens B. 48.  2001. Fat utilization during exercise: adaptation to a fat-rich diet increases utilization of plasma fatty acids and very low density lipoprotein-triacylglycerol in humans. J. Physiol. 537:1009–20 [Google Scholar]
  49. Hirsch AH, Rosen OM. 49.  1984. Lipolytic stimulation modulates the subcellular distribution of hormone-sensitive lipase in 3T3-L1 cells. J. Lipid Res. 25:665–77 [Google Scholar]
  50. Hoppeler H. 50.  1999. Skeletal muscle substrate metabolism. Int. J. Obes. Relat. Metab. Disord. 23:Suppl. 3S7–10 [Google Scholar]
  51. Hulver MW, Berggren JR, Cortright RN, Dudek RW, Thompson RP. 51.  et al. 2003. Skeletal muscle lipid metabolism with obesity. Am. J. Physiol. Endocrinol. Metab. 284:E741–47 [Google Scholar]
  52. Hulver MW, Dohm GL. 52.  2004. The molecular mechanism linking muscle fat accumulation to insulin resistance. Proc. Nutr. Soc. 63:375–80 [Google Scholar]
  53. Hurley BF, Nemeth PM, Martin WH III, Hagberg JM, Dalsky GP, Holloszy JO. 53.  1986. Muscle triglyceride utilization during exercise: effect of training. J. Appl. Physiol. 60:562–67 [Google Scholar]
  54. Jeukendrup AE. 54.  2004. Carbohydrate intake during exercise and performance. Nutrition 20:669–77 [Google Scholar]
  55. Jocken JW, Blaak EE. 55.  2008. Catecholamine-induced lipolysis in adipose tissue and skeletal muscle in obesity. Physiol. Behav. 94:219–30 [Google Scholar]
  56. Jocken JW, Smit E, Goossens GH, Essers YP, van Baak MA. 56.  et al. 2008. Adipose triglyceride lipase (ATGL) expression in human skeletal muscle is type I (oxidative) fiber specific. Histochem. Cell Biol. 129:535–38 [Google Scholar]
  57. Johnson NA, Stannard SR, Rowlands DS, Chapman PG, Thompson CH. 57.  et al. 2006. Effect of short-term starvation versus high-fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men. Exp. Physiol. 91:693–703 [Google Scholar]
  58. Kelley DE, Simoneau JA. 58.  1994. Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. J. Clin. Invest. 94:2349–56 [Google Scholar]
  59. Kennedy A, Martinez K, Chuang CC, LaPoint K, McIntosh M. 59.  2009. Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J. Nutr. 139:1–4 [Google Scholar]
  60. Kienesberger PC, Lee D, Pulinilkunnil T, Brenner DS, Cai L. 60.  et al. 2009. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. J. Biol. Chem. 284:30218–29 [Google Scholar]
  61. Kiens B. 61.  2006. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol. Rev. 86:205–43 [Google Scholar]
  62. Kiens B, Essen-Gustavsson B, Christensen NJ, Saltin B. 62.  1993. Skeletal muscle substrate utilization during submaximal exercise in man: effect of endurance training. J. Physiol. 469:459–78 [Google Scholar]
  63. Klein S, Coyle EF, Wolfe RR. 63.  1994. Fat metabolism during low-intensity exercise in endurance-trained and untrained men. Am. J. Physiol. 267:E934–40 [Google Scholar]
  64. Koopman R, Manders RJ, Jonkers RA, Hul GB, Kuipers H, van Loon LJ. 64.  2006. Intramyocellular lipid and glycogen content are reduced following resistance exercise in untrained healthy males. Eur. J. Appl. Physiol. 96:525–34 [Google Scholar]
  65. Langfort J, Ploug T, Ihlemann J, Baranczuk E, Donsmark M. 65.  et al. 2003. Additivity of adrenaline and contractions on hormone-sensitive lipase, but not on glycogen phosphorylase, in rat muscle. Acta Physiol. Scand. 178:51–60 [Google Scholar]
  66. Langfort J, Ploug T, Ihlemann J, Enevoldsen LH, Stallknecht B. 66.  et al. 1998. Hormone-sensitive lipase (HSL) expression and regulation in skeletal muscle. Adv. Exp. Med. Biol. 441:219–28 [Google Scholar]
  67. Langfort J, Ploug T, Ihlemann J, Holm C, Galbo H. 67.  2000. Stimulation of hormone-sensitive lipase activity by contractions in rat skeletal muscle. Biochem. J. 351:207–14 [Google Scholar]
  68. Langfort J, Ploug T, Ihlemann J, Saldo M, Holm C, Galbo H. 68.  1999. Expression of hormone-sensitive lipase and its regulation by adrenaline in skeletal muscle. Biochem. J. 340:Pt. 2459–65 [Google Scholar]
  69. Lara-Castro C, Newcomer BR, Rowell J, Wallace P, Shaughnessy SM. 69.  et al. 2008. Effects of short-term very low-calorie diet on intramyocellular lipid and insulin sensitivity in nondiabetic and type 2 diabetic subjects. Metabolism 57:1–8 [Google Scholar]
  70. Larson-Meyer DE, Newcomer BR, Hunter GR. 70.  2002. Influence of endurance running and recovery diet on intramyocellular lipid content in women: a 1H NMR study. Am. J. Physiol. Endocrinol. Metab. 282:E95–106 [Google Scholar]
  71. Lee JS, Pinnamaneni SK, Eo SJ, Cho IH, Pyo JH. 71.  et al. 2006. Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J. Appl. Physiol. 100:1467–74 [Google Scholar]
  72. Linden D, William-Olsson L, Rhedin M, Asztely AK, Clapham JC, Schreyer S. 72.  2004. Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis. J. Lipid Res. 45:1279–88 [Google Scholar]
  73. Liu L, Zhang Y, Chen N, Shi X, Tsang B, Yu YH. 73.  2007. Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J. Clin. Invest. 117:1679–89 [Google Scholar]
  74. Liu L, Shi X, Bharadwaj KG, Ikeda S, Yamashita H. 74.  et al. 2009. DGAT1 expression increases heart triglyceride content but ameliorates lipotoxicity. J. Biol. Chem. 284:36312–23 [Google Scholar]
  75. Martin WH III, Dalsky GP, Hurley BF, Matthews DE, Bier DM. 75.  et al. 1993. Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise. Am. J. Physiol. 265:E708–14 [Google Scholar]
  76. Meex RCR, Schrauwen P, Hesselink MKC. 76.  2009. Modulation of myocellular fat stores: lipid droplet dynamics in health and disease. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297:R913–24 [Google Scholar]
  77. Moberg E, Sjoberg S, Hagstrom-Toft E, Bolinder J. 77.  2002. No apparent suppression by insulin of in vivo skeletal muscle lipolysis in nonobese women. Am. J. Physiol. Endocrinol. Metab. 283:E295–301 [Google Scholar]
  78. Moro C, Bajpeyi S, Smith SR. 78.  2008. Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity. Am. J. Physiol. Endocrinol. Metab. 294:E203–13 [Google Scholar]
  79. Moro C, Galgani JE, Luu L, Pasarica M, Mairal A. 79.  et al. 2009. Influence of gender, obesity, and muscle lipase activity on intramyocellular lipids in sedentary individuals. J. Clin. Endocrinol. Metab. 94:3440–47 [Google Scholar]
  80. Muoio DM, Dohm GL, Tapscott EB, Coleman RA. 80.  1999. Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob/ob mice. Am. J. Physiol. Endocrinol. Metab. 276:E913–21 [Google Scholar]
  81. Olofsson SO, Boström P, Andersson L, Rutberg M, Perman J, Borén J. 81.  2009. Lipid droplets as dynamic organelles connecting storage and efflux of lipids. Biochim. Biophys. Acta 1791:448–58 [Google Scholar]
  82. Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA. 82.  et al. 1997. Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46:983–88 [Google Scholar]
  83. Pehleman TL, Peters SJ, Heigenhauser GJ, Spriet LL. 83.  2005. Enzymatic regulation of glucose disposal in human skeletal muscle after a high-fat, low-carbohydrate diet. J. Appl. Physiol. 98:100–7 [Google Scholar]
  84. Peters SJ, Harris RA, Wu P, Pehleman TL, Heigenhauser GJ, Spriet LL. 84.  2001. Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet. Am. J. Physiol. Endocrinol. Metab. 281:E1151–58 [Google Scholar]
  85. Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. 85.  2005. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 54:603–8 [Google Scholar]
  86. Phillips DI, Caddy S, Ilic V, Fielding BA, Frayn KN. 86.  et al. 1996. Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. Metabolism 45:947–50 [Google Scholar]
  87. Phillips SM, Green HJ, Tarnopolsky MA, Heigenhauser GF, Hill RE, Grant SM. 87.  1996. Effects of training duration on substrate turnover and oxidation during exercise. J. Appl. Physiol. 81:2182–91 [Google Scholar]
  88. Prats C, Donsmark M, Qvortrup K, Londos C, Sztalryd C. 88.  et al. 2006. Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine. J. Lipid Res. 47:2392–99 [Google Scholar]
  89. Pruchnic R, Katsiaras A, He J, Kelley DE, Winters C, Goodpaster BH. 89.  2004. Exercise training increases intramyocellular lipid and oxidative capacity in older adults. Am. J. Physiol. Endocrinol. Metab. 287:E857–62 [Google Scholar]
  90. Rabol R, Svendsen PF, Skovbro M, Boushel R, Haugaard SB. 90.  et al. 2009. Reduced skeletal muscle mitochondrial respiration and improved glucose metabolism in nondiabetic obese women during a very low calorie dietary intervention leading to rapid weight loss. Metabolism 58:1145–52 [Google Scholar]
  91. Randle PJ, Garland PB, Hales CN, Newsholme EA. 91.  1963. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–89 [Google Scholar]
  92. Roepstorff C, Donsmark M, Thiele M, Vistisen B, Stewart G. 92.  et al. 2006. Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise. Am. J. Physiol. Endocrinol. Metab. 291:E1106–14 [Google Scholar]
  93. Roepstorff C, Vistisen B, Donsmark M, Nielsen JN, Galbo H. 93.  et al. 2004. Regulation of hormone-sensitive lipase activity and Ser563 and Ser565 phosphorylation in human skeletal muscle during exercise. J. Physiol. 560:551–62 [Google Scholar]
  94. Sacchetti M, Saltin B, Osada T, van HG. 94.  2002. Intramuscular fatty acid metabolism in contracting and non-contracting human skeletal muscle. J. Physiol. 540:387–95 [Google Scholar]
  95. Schenk S, Horowitz JF. 95.  2007. Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J. Clin. Invest. 117:1690–98 [Google Scholar]
  96. Schenk S, Saberi M, Olefsky JM. 96.  2008. Insulin sensitivity: modulation by nutrients and inflammation. J. Clin. Invest. 118:2992–3002 [Google Scholar]
  97. Schmitz-Peiffer C, Craig DL, Biden TJ. 97.  1999. Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J. Biol. Chem. 274:24202–10 [Google Scholar]
  98. Schrauwen P, van Aggel-Leijssen DPC, Hul G, Wagenmakers AJM, Vidal H. 98.  et al. 2002. The effect of a 3-month low-intensity endurance training program on fat oxidation and acetyl-CoA carboxylase-2 expression. Diabetes 51:2220–26 [Google Scholar]
  99. Schrauwen-Hinderling VB, Schrauwen P, Hesselink MKC, van Engelshoven JMA, Nicolay K. 99.  et al. 2003. The increase in intramyocellular lipid content is a very early response to training. J. Clin. Endocrinol. Metab. 88:1610–16 [Google Scholar]
  100. Schrauwen-Hinderling VB, van Loon LJ, Koopman R, Nicolay K, Saris WH, Kooi ME. 100.  2003. Intramyocellular lipid content is increased after exercise in nonexercising human skeletal muscle. J. Appl. Physiol. 95:2328–32 [Google Scholar]
  101. Schrauwen-Hinderling VB, Kooi ME, Hesselink MKC, Moonen-Kornips E, Schaart G. 101.  et al. 2005. Intramyocellular lipid content and molecular adaptations in response to a 1-week high-fat diet. Obesity 13:2088–94 [Google Scholar]
  102. Shaw CS, Jones DA, Wagenmakers AJ. 102.  2008. Network distribution of mitochondria and lipid droplets in human muscle fibres. Histochem. Cell Biol. 129:65–72 [Google Scholar]
  103. Shaw CS, Sherlock M, Stewart PM, Wagenmakers AJ. 103.  2009. Adipophilin distribution and colocalization with lipid droplets in skeletal muscle. Histochem. Cell Biol. 131:575–81 [Google Scholar]
  104. Shulman GI. 104.  2000. Cellular mechanisms of insulin resistance. J. Clin. Invest. 106:171–76 [Google Scholar]
  105. Sollner TH. 105.  2007. Lipid droplets highjack SNAREs. Nat. Cell Biol. 9:1219–20 [Google Scholar]
  106. Solomon TP, Sistrun SN, Krishnan RK, Del Aguila LF, Marchetti CM. 106.  et al. 2008. Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults. J. Appl. Physiol. 104:1313–19 [Google Scholar]
  107. Stannard SR, Thompson MW, Fairbairn K, Huard B, Sachinwalla T, Thompson CH. 107.  2002. Fasting for 72 h increases intramyocellular lipid content in nondiabetic, physically fit men. Am. J. Physiol. Endocrinol. Metab. 283:E1185–91 [Google Scholar]
  108. Starling RD, Trappe TA, Parcell AC, Kerr CG, Fink WJ, Costill DL. 108.  1997. Effects of diet on muscle triglyceride and endurance performance. J. Appl. Physiol. 82:1185–89 [Google Scholar]
  109. Steffensen CH, Roepstorff C, Madsen M, Kiens B. 109.  2002. Myocellular triacylglycerol breakdown in females but not in males during exercise. Am. J. Physiol. Endocrinol. Metab. 282:E634–42 [Google Scholar]
  110. Stellingwerff T, Boon H, Gijsen AP, Stegen JH, Kuipers H, van Loon LJ. 110.  2007. Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use. Pflugers Arch. 454:635–47 [Google Scholar]
  111. Stellingwerff T, Boon H, Jonkers RA, Senden JM, Spriet LL. 111.  et al. 2007. Significant intramyocellular lipid use during prolonged cycling in endurance-trained males as assessed by three different methodologies. Am. J. Physiol. Endocrinol. Metab. 292:E1715–23 [Google Scholar]
  112. Stettler R, Ith M, Acheson KJ, Decombaz J, Boesch C. 112.  et al. 2005. Interaction between dietary lipids and physical inactivity on insulin sensitivity and on intramyocellular lipids in healthy men. Diabetes Care 28:1404–9 [Google Scholar]
  113. Stevenson EJ, Thelwall PE, Thomas K, Smith F, Brand-Miller J, Trenell MI. 113.  2009. Dietary glycemic index influences lipid oxidation but not muscle or liver glycogen oxidation during exercise. Am. J. Physiol. Endocrinol. Metab. 296:E1140–47 [Google Scholar]
  114. Sztalryd C, Xu G, Dorward H, Tansey JT, Contreras JA. 114.  et al. 2003. Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation. J. Cell Biol. 161:1093–103 [Google Scholar]
  115. Takeuchi K, Reue K. 115.  2009. Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am. J. Physiol. Endocrinol. Metab. 296:E1195–209 [Google Scholar]
  116. Tamura Y, Tanaka Y, Sato F, Choi JB, Watada H. 116.  et al. 2005. Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J. Clin. Endocrinol. Metab. 90:3191–96 [Google Scholar]
  117. Tarnopolsky MA, Rennie CD, Robertshaw HA, Fedak-Tarnopolsky SN, Devries MC, Hamadeh MJ. 117.  2007. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292:R1271–78 [Google Scholar]
  118. Thrush AB, Brindley DN, Chabowski A, Heigenhauser GJ, Dyck DJ. 118.  2009. Skeletal muscle lipogenic protein expression is not different between lean and obese individuals; a potential factor in ceramide accumulation. J. Clin. Endocrinol. Metab. 94:5053–61 [Google Scholar]
  119. Trenell MI, Stevenson E, Stockmann K, Brand-Miller J. 119.  2008. Effect of high and low glycaemic index recovery diets on intramuscular lipid oxidation during aerobic exercise. Br. J. Nutr. 99:326–32 [Google Scholar]
  120. van Loon LJ. 120.  2004. Use of intramuscular triacylglycerol as a substrate source during exercise in humans. J. Appl. Physiol. 97:1170–87 [Google Scholar]
  121. van Loon LJ, Greenhaff PL, Constantin-Teodosiu D, Saris WH, Wagenmakers AJ. 121.  2001. The effects of increasing exercise intensity on muscle fuel utilisation in humans. J. Physiol. 536:295–304 [Google Scholar]
  122. van Loon LJ, Koopman R, Manders R, van der Weegen W, van Kranenburg GP, Keizer HA. 122.  2004. Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes. Am. J. Physiol. Endocrinol. Metab. 287:E558–65 [Google Scholar]
  123. van Loon LJ, Koopman R, Stegen JH, Wagenmakers AJ, Keizer HA, Saris WH. 123.  2003. Intramyocellular lipids form an important substrate source during moderate intensity exercise in endurance-trained males in a fasted state. J. Physiol. 553:611–25 [Google Scholar]
  124. van Loon LJ, Manders RJ, Koopman R, Kaastra B, Stegen JH. 124.  et al. 2005. Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients. Diabetologia 48:2097–107 [Google Scholar]
  125. van Loon LJ, Schrauwen-Hinderling VB, Koopman R, Wagenmakers AJ, Hesselink MK. 125.  et al. 2003. Influence of prolonged endurance cycling and recovery diet on intramuscular triglyceride content in trained males. Am. J. Physiol. Endocrinol. Metab. 285:E804–11 [Google Scholar]
  126. van Loon LJ, Thomason-Hughes M, Constantin-Teodosiu D, Koopman R, Greenhaff PL. 126.  et al. 2005. Inhibition of adipose tissue lipolysis increases intramuscular lipid and glycogen use in vivo in humans. Am. J. Physiol. Endocrinol. Metab. 289:E482–93 [Google Scholar]
  127. Varma V, Yao-Borengasser A, Rasouli N, Nolen GT, Phanavanh B. 127.  et al. 2009. Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action. Am. J. Physiol. Endocrinol. Metab. 296:E1300–10 [Google Scholar]
  128. Vessby B, Unsitupa M, Hermansen K, Riccardi G, Rivellese AA. 128.  et al. 2001. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU Study. Diabetologia 44:312–19 [Google Scholar]
  129. Vogt M, Puntschart A, Howald H, Mueller B, Mannhart C. 129.  et al. 2003. Effects of dietary fat on muscle substrates, metabolism, and performance in athletes. Med. Sci. Sports Exerc. 35:952–60 [Google Scholar]
  130. Walther TC, Farese J. 130.  2009. The life of lipid droplets. Biochim. Biophys. Acta 1791:459–66 [Google Scholar]
  131. Watt MJ. 131.  2009. Storing up trouble: Does accumulation of intramyocellular triglyceride protect skeletal muscle from insulin resistance?. Clin. Exp. Pharmacol. Physiol. 36:5–11 [Google Scholar]
  132. Watt MJ, Heigenhauser GJ, Dyck DJ, Spriet LL. 132.  2002. Intramuscular triacylglycerol, glycogen and acetyl group metabolism during 4 h of moderate exercise in man. J. Physiol. 541:969–78 [Google Scholar]
  133. Watt MJ, Heigenhauser GJ, O'Neill M, Spriet LL. 133.  2003. Hormone-sensitive lipase activity and fatty acyl-CoA content in human skeletal muscle during prolonged exercise. J. Appl. Physiol. 95:314–21 [Google Scholar]
  134. Watt MJ, Heigenhauser GJ, Spriet LL. 134.  2002. Intramuscular triacylglycerol utilization in human skeletal muscle during exercise: Is there a controversy?. J. Appl. Physiol. 93:1185–95 [Google Scholar]
  135. Watt MJ, Heigenhauser GJ, Spriet LL. 135.  2003. Effects of dynamic exercise intensity on the activation of hormone-sensitive lipase in human skeletal muscle. J. Physiol. 547:301–8 [Google Scholar]
  136. Watt MJ, Holmes AG, Pinnamaneni SK, Garnham AP, Steinberg GR. 136.  et al. 2006. Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue. Am. J. Physiol. Endocrinol. Metab. 290:E500–8 [Google Scholar]
  137. Watt MJ, Holmes AG, Steinberg GR, Mesa JL, Kemp BE, Febbraio MA. 137.  2004. Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 287:E120–27 [Google Scholar]
  138. Watt MJ, Krustrup P, Secher NH, Saltin B, Pedersen BK, Febbraio MA. 138.  2004. Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 286:E144–50 [Google Scholar]
  139. Watt MJ, Steinberg GR, Chan S, Garnham A, Kemp BE, Febbraio MA. 139.  2004. Beta-adrenergic stimulation of skeletal muscle HSL can be overridden by AMPK signaling. FASEB J. 18:1445–46 [Google Scholar]
  140. Wendel AA, Lewin TM, Coleman RA. 140.  2009. Glycerol-3-phosphate acyltransferases: rate limiting enzymes of triacylglycerol biosynthesis. Biochim. Biophys. Acta 1791:501–6 [Google Scholar]
  141. Wolins NE, Brasaemle DL, Bickel PE. 141.  2006. A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Lett. 580:5484–91 [Google Scholar]
  142. Yu C, Chen Y, Cline GW, Zhang D, Zong H. 142.  et al. 2002. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J. Biol. Chem. 277:50230–36 [Google Scholar]
  143. Zderic TW, Davidson CJ, Schenk S, Byerley LO, Coyle EF. 143.  2004. High-fat diet elevates resting intramuscular triglyceride concentration and whole body lipolysis during exercise. Am. J. Physiol. Endocrinol. Metab. 286:E217–25 [Google Scholar]
  144. Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R. 144.  et al. 2004. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306:1383–86 [Google Scholar]
/content/journals/10.1146/annurev.nutr.012809.104817
Loading
The Effect of Exercise and Nutrition on Intramuscular Fat Metabolism and Insulin Sensitivity
Annual Review of Nutrition 30, 13 (2010); https://doi.org/10.1146/annurev.nutr.012809.104817
/content/journals/10.1146/annurev.nutr.012809.104817
/content/journals/10.1146/annurev.nutr.012809.104817
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error