Abstract

Skeletal muscle is the main tissue responsible for insulin-stimulated glucose uptake. Consumption of a high-fat diet rich in saturated fats (HFD) and obesity are associated with accumulation of intramuscular lipids that leads to several disorders, e.g. insulin resistance (IRes) and type 2 diabetes (T2D). The mechanism underlying the induction of IRes is still unknown. It was speculated that accumulation of intramuscular triacylglycerols (TAG) is linked to induction of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramides (Cer). It has been demonstrated that accumulation of each of the above-mentioned lipid classes negatively affects the insulin signaling pathway. It is not clear which of those lipids play the most important role in HFD-induced skeletal muscle IRes. The aim of the present work is to present the current knowledge of the role of adipose tissue and excess of fatty acids in the induction of insulin resistance.

References

• 1. Abumrad N., Harmon C., Ibrahimi A.: Membrane transport oflong-chain fatty acids: evidence for a facilitated process. J. LipidRes., 1998; 39: 2309-2318
  Google Scholar
• 2. Adams J.M., Pratipanawatr T., Berria R., Wang E., DeFronzo R.A.,Sullards M.C., Mandarino L.J.: Ceramide content is increased in skeletalmuscle from obese insulin-resistant humans. Diabetes, 2004;53: 25-31
  Google Scholar
• 3. Axelsson J., Heimbürger O., Lindholm B., Stenvinkel P.: Adiposetissue and its relation to inflammation: the role of adipokines. J. Ren.Nutr., 2005; 15: 131-136
  Google Scholar
• 4. Belfort R., Mandarino L., Kashyap S., Wirfel K., Pratipanawatr T.,Berria R., Defronzo R.A., Cusi K.: Dose-response effect of elevated plasmafree fatty acid on insulin signaling. Diabetes, 2005; 54: 1640-1648
  Google Scholar
• 5. Björntorp P.: Metabolic implications of body fat distribution.Diabetes Care, 1991; 14: 1132-1143
  Google Scholar
• 6. Błachnio-Zabielska A.U., Baranowski M., Hirnle T., Zabielski P.,Lewczuk A., Dmitruk I., Górski J.: Increased bioactive lipids contentin human subcutaneous and epicardial fat tissue correlates withinsulin resistance. Lipids, 2012; 47: 1131-1141
  Google Scholar
• 7. Blachnio-Zabielska A., Baranowski M., Zabielski P., Gorski J.: EffectPiśmiennictwoof high fat diet enriched with unsaturated and diet rich in saturatedfatty acids on sphingolipid metabolism in rat skeletal muscle. J.Cell.Physiol., 2010; 225: 786-791
  Google Scholar
• 8. Blachnio-Zabielska A.U., Koutsari C., Tchkonia T., Jensen M.D.:Sphingolipid content of human adipose tissue: relationship to adiponectinand insulin resistance. Obesity, 2012; 20: 2341-2347
  Google Scholar
• 9. Błachnio-Zabielska A.U., Pułka M., Baranowski M., Nikołajuk A.,Zabielski P., Górska M., Górski J.: Ceramide metabolism is affectedby obesity and diabetes in human adipose tissue. J. Cell. Physiol.,2012; 227: 550-557
  Google Scholar
• 10. Bonen A., Miskovic D., Kiens B.: Fatty acid transporters (FABPpm,FAT, FATP) in human muscle. Can. J. Appl. Physiol., 1999; 24: 515-523
  Google Scholar
• 11. Bonzón-Kulichenko E., Schwudke D., Gallardo N., Moltó E., Fernández-AgullóT., Shevchenko A., Andrés A.: Central leptin regulatestotal ceramide content and sterol regulatory element bindingprotein-1C proteolytic maturation in rat white adipose tissue. Endocrinology,2009; 150: 169-178
  Google Scholar
• 12. Bruce C.R., Anderson M.J., Carey A.L., Newman D.G., Bonen A.,Kriketos A.D., Cooney G.J., Hawley J.A.: Muscle oxidative capacityis a better predictor of insulin sensitivity than lipid status. J. Clin.Endocrinol. Metab., 2003; 88: 5444-5451
  Google Scholar
• 13. Bruce C.R., Brolin C., Turner N., Cleasby M.E., van der Leij F.R.,Cooney G.J., Kraegen E.W.: Overexpression of carnitine palmitoyltransferaseI in skeletal muscle in vivo increases fatty acid oxidationand reduces triacylglycerol esterification. Am. J. Physiol. Endocrinol.Metab., 2007; 292: E1231-E1237
  Google Scholar
• 14. Chang L., Chiang S.H., Saltiel A.R.: Insulin signaling and the regulationof glucose transport. Mol Med., 2004; 10: 65-71
  Google Scholar
• 15. Choi C.S., Savage D.B., Abu-Elheiga L., Liu Z.X., Kim S., KulkarniA., Distefano A., Hwang Y.J., Reznick R.M., Codella R., Zhang D., ClineG.W., Wakil S.J., Shulman G.I.: Continuous fat oxidation in acetyl-CoAcarboxylase 2 knockout mice increases total energy expenditure,reduces fat mass, and improves insulin sensitivity. Proc. Natl. Acad.Sci. USA, 2007; 104: 16480-16485
  Google Scholar
• 16. Consitt L.A., Bell J.A., Houmard J.A.: Intramuscular lipid metabolism,insulin action, and obesity. IUBMB Life, 2009; 61: 47-55
  Google Scholar
• 17. DeFronzo R.A., Jacot E., Jequier E., Maeder E., Wahren J., FelberJ.P.: The effect of insulin on the disposal of intravenous glucose.Results from indirect calorimetry and hepatic and femoral venouscatheterization. Diabetes, 1981; 30: 1000-1007
  Google Scholar
• 18. Dohm G.L., Tapscott E.B., Pories W.J., Dabbs D.J., FlickingerE.G., Meelheim D., Fushiki T., Atkinson S.M., Elton C.W., Caro J.F.:An in vitro human muscle preparation suitable for metabolic studies.Decreased insulin stimulation of glucose transport in musclefrom morbidly obese and diabetic subjects. J. Clin. Invest., 1988;82: 486-494
  Google Scholar
• 19. Ellis B.A., Poynten A., Lowy A.J., Furler S.M., Chisholm D.J., KraegenE.W., Cooney G.J.: Long-chain acyl-CoA esters as indicators oflipid metabolism and insulin sensitivity in rat and human muscle.Am. J. Physiol. Endocrinol. Metab., 2000; 279: E554-E560
  Google Scholar
• 20. Folli F., Saad M.J., Backer J.M., Kahn C.R.: Insulin stimulation ofphosphatidylinositol 3-kinase activity and association with insulinreceptor substrate 1 in liver and muscle of the intact rat. J. Biol.Chem., 1992; 267: 22171-22177
  Google Scholar
• 21. Frøsig C., Rose A.J., Treebak J.T., Kiens B., Richter E.A., WojtaszewskiJ.F.: Effects of endurance exercise training on insulin signalingin human skeletal muscle: interactions at the level of phosphatidylinositol3-kinase, Akt, and AS160. Diabetes, 2007; 56: 2093-2102
  Google Scholar
• 22. Goodpaster B.H., Kelley D.E.: Skeletal muscle triglyceride: markeror mediator of obesity-induced insulin resistance in type 2 diabetesmellitus? Curr. Diab. Rep., 2002; 2: 216-222
  Google Scholar
• 23. Hamilton J.A.: Fatty acid transport: difficult or easy? J. LipidRes., 1998; 39: 467-481
  Google Scholar
• 24. Hotamisligil G.S.: Molecular mechanisms of insulin resistanceand the role of the adipocyte. Int. J. Obes. Relat. Metab. Disord., 2000;4, 24 Suppl.: S23-S27
  Google Scholar
• 25. Hotamisligil G.S., Shargill N.S., Spiegelman B.M.: Adipose expressionof tumor necrosis factor-α: direct role in obesity-linked insulinresistance. Science, 1993; 259: 87-91
  Google Scholar
• 26. Ipavec-Levasseur S., Croci I., Choquette S., Byrne N.M., CowinG., O’Moore-Sullivan T.M., Prins J.B., Hickman I.J.: Effect of 1-h moderate-intensityaerobic exercise on intramyocellular lipids in obesemen before and after a lifestyle intervention. Appl. Physiol. Nutr.Metab., 2015; 40: 1262-1268
  Google Scholar
• 27. Jeukendrup A.E.: Regulation of fat metabolism in skeletal muscle.Ann. N.Y. Acad. Sci., 2002; 967: 217-235
  Google Scholar
• 28. Kershaw E.E., Flier J.S.: Adipose tissue as an endocrine organ. J.Clin. Endocrinol. Metab., 2004; 89: 2548-2556
  Google Scholar
• 29. Kolak M., Westerbacka J., Velagapudi V.R., Wågsäter D., YetukuriL., Makkonen J., Rissanen A., Häkkinen A.M., Lindell M., BergholmR., Hamsten A., Eriksson P., Fisher R.M., Oresic M., Yki-Järvinen H.:Adipose tissue inflammation and increased ceramide content characterizesubjects with high liver fat content independent of obesity.Diabetes, 2007; 56: 1960-1968
  Google Scholar
• 30. Kolesnick R., Fuks Z.: Radiation and ceramide-induced apoptosis.Oncogene, 2003; 22: 5897-5906
  Google Scholar
• 31. Kramer H.F., Witczak C.A., Taylor E.B., Fujii N., Hirshman M.F.,Goodyear L.J.: AS160 regulates insulin- and contraction-stimulatedglucose uptake in mouse skeletal muscle. J. Biol. Chem., 2006; 281:31478-31485
  Google Scholar
• 32. Lanza I.R., Blachnio-Zabielska A., Johnson M.L., Schimke J.M.,Jakaitis D.R., Lebrasseur N.K., Jensen M.D., Nair K.S., Zabielski P.: Influenceof fish oil on skeletal muscle mitochondrial energetics andlipid metabolites during high-fat diet. Am. J. Physiol. Endocrinol.Metab., 2013; 304: E1391-E1403
  Google Scholar
• 33. Lefort N., Glancy B., Bowen B., Willis W.T., Bailowitz Z., De FilippisE.A., Brophy C., Meyer C., Højlund K., Yi Z., Mandarino L.J.:Increased reactive oxygen species production and lower abundanceof complex I subunits and carnitine palmitoyltransferase 1B proteindespite normal mitochondrial respiration in insulin-resistant humanskeletal muscle. Diabetes, 2010; 59: 2444-2452
  Google Scholar
• 34. Lin J., Choi Y.H., Hartzell D.L., Li C., Della-Fera M.A., Baile C.A.: CNSmelanocortin and leptin effects on stearoyl-CoA desaturase-1 and resistinexpression. Biochem. Biophys. Res. Commun., 2003; 311: 324-328
  Google Scholar
• 35. Long S.D., Pekala P.H.: Lipid mediators of insulin resistance:ceramide signalling down-regulates GLUT4 gene transcription in3T3-L1 adipocytes. Biochem. J., 1996; 319: 179-184
  Google Scholar
• 36. MacRae V.E., Burdon T., Ahmed S.F., Farquharson C.: Ceramideinhibition of chondrocyte proliferation and bone growth is IGF-Iindependent. J. Endocrinol., 2006; 191: 369-377
  Google Scholar
• 37. McGarry J.D., Brown N.F.: The mitochondrial carnitine palmitoyltransferasesystem. From concept to molecular analysis. Eur. J.Biochem., 1997; 244: 1-14
  Google Scholar
• 38. Oakes N.D., Bell K.S., Furler S.M., Camilleri S., Saha A.K., RudermanN.B., Chisholm D.J., Kraegen E.W.: Diet-induced muscle insulinresistance in rats is ameliorated by acute dietary lipid withdrawalor a single bout of exercise: parallel relationship between insulinstimulation of glucose uptake and suppression of long-chain fattyacyl-CoA. Diabetes, 1997; 46: 2022-2028
  Google Scholar
• 39. Oakes N.D., Kennedy C.J., Jenkins A.B., Laybutt D.R., ChisholmD.J., Kraegen E.W.: A new antidiabetic agent, BRL 49653, reduces lipidavailability and improves insulin action and glucoregulation inthe rat. Diabetes, 1994; 43: 1203-1210
  Google Scholar
• 40. Oh H.L., Seok J.Y., Kwon C.H., Kang S.K., Kim Y.K.: Role of MAPKin ceramide-induced cell death in primary cultured astrocytes frommouse embryonic brain. Neurotoxicology, 2006; 27: 31-38
  Google Scholar
• 41. Perdomo G., Commerford S.R., Richard A.M., Adams S.H., CorkeyB.E., O’Doherty R.M., Brown N.F.: Increased β-oxidation in musclecells enhances insulin-stimulated glucose metabolism and protectsagainst fatty acid-induced insulin resistance despite intramyocellularlipid accumulation. J. Biol. Chem., 2004; 279: 27177-27186
  Google Scholar
• 42. Ramsay R.R., Zammit V.A.: Carnitine acyltransferases and theirinfluence on CoA pools in health and disease. Mol. Aspects Med.,2004; 25: 475-493
  Google Scholar
• 43. Roepstorff C., Helge J.W., Vistisen B., Kiens B.: Studies of plasmamembrane fatty acid-binding protein and other lipid-binding proteinsin human skeletal muscle. Proc. Nutr. Soc., 2004; 63: 239-244
  Google Scholar
• 44. Samad F., Badeanlou L., Shah C., Yang G.: Adipose tissue and ceramidebiosynthesis in the pathogenesis of obesity. Adv. Exp. Med.Biol., 2011; 721: 67-86
  Google Scholar
• 45. Samad F., Hester K.D., Yang G., Hannun Y.A., Bielawski J.: Alteredadipose and plasma sphingolipid metabolism in obesity: a potentialmechanism for cardiovascular and metabolic risk. Diabetes,2006; 55: 2579-2587
  Google Scholar
• 46. Samad F., Loskutoff D.J.: Tissue distribution and regulation ofplasminogen activator inhibitor-1 in obese mice. Mol. Med., 1996;2: 568-582
  Google Scholar
• 47. Savage D.B., Petersen K.F., Shulman G.I.: Disordered lipid metabolismand the pathogenesis of insulin resistance. Physiol. Rev.,2007; 87: 507-520
  Google Scholar
• 48. Schmitz-Peiffer C.: Protein kinase C and lipid-induced insulinresistance in skeletal muscle. Ann. N.Y. Acad. Sci., 2002;967: 146-157
  Google Scholar
• 49. Schmitz-Peiffer C., Browne C.L., Oakes N.D., Watkinson A., ChisholmD.J., Kraegen E.W., Biden T.J.: Alterations in the expressionand cellular localization of protein kinase C isozymes ε and θ areassociated with insulin resistance in skeletal muscle of the high-fat–fed rat. Diabetes, 1997; 46: 169-178
  Google Scholar
• 50. Schwieterman W., Sorrentino D., Potter B.J., Rand J., Kiang C.L.,Stump D., Berk P.D.: Uptake of oleate by isolated rat adipocytes ismediated by a 40-kDa plasma membrane fatty acid binding proteinclosely related to that in liver and gut. Proc. Natl. Acad. Sci. USA,1988; 85: 359-363
  Google Scholar
• 51. Seufert J.: Leptin effects on pancreatic β-cell gene expressionand function. Diabetes, 2004; 53, Suppl. 1: S152-S158
  Google Scholar
• 52. Simoneau J.A., Veerkamp J.H., Turcotte L.P., Kelley D.E.: Markersof capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. FASEBJ., 1999; 13: 2051-2060
  Google Scholar
• 53. Straczkowski M., Kowalska I., Nikolajuk A., Dzienis-StraczkowskaS., Kinalska I., Baranowski M., Zendzian-Piotrowska M., Brzezinska Z.,Gorski J.: Relationship between insulin sensitivity and sphingomyelin signalingpathway in human skeletal muscle. Diabetes, 2004; 53: 1215-1221
  Google Scholar
• 54. Timmers S., Schrauwen P., de Vogel J.: Muscular diacylglycerolmetabolism and insulin resistance. Physiol. Behav., 2008; 94: 242-251
  Google Scholar
• 55. Turinsky J., O’Sullivan D.M., Bayly B.P.: 1,2-Diacylglycerol andceramide levels in insulin-resistant tissues of the rat in vivo. J. Biol.Chem., 1990; 265: 16880-16885
  Google Scholar
• 56. Yu C., Chen Y., Cline G.W., Zhang D., Zong H., Wang Y., BergeronR., Kim J.K., Cushman S.W., Cooney G.J., Atcheson B., White M.F.,Kraegen E.W., Shulman G.I.: Mechanism by which fatty acids inhibitinsulin activation of insulin receptor substrate-1 (IRS-1)-associatedphosphatidylinositol 3-kinase activity in muscle. J. Biol. Chem., 2002;277: 50230-50236
  Google Scholar

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