Skeletal intramyocellular lipid metabolism and insulin resistance

Yiran Li1,2, Shimeng Xu3,2, Xuelin Zhang4, Zhengfang Yi1, Simon Cichello5
1Department of Biological Science and Biotechnology, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
2National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
3University of Chinese Academy of Sciences, Beijing, China
4Capital University of Physical Education and Sport, Beijing, China
5School of Life Sciences, La Trobe University, Melbourne, Australia

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Adams JM, Pratipanawatr T, Berria R, Wang E, DeFronzo RA, Sullards MC, Mandarino LJ (2004) Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 53(1):25–31

Amati F, Dube JJ, Alvarez-Carnero E, Edreira MM, Chomentowski P, Coen PM, Switzer GE, Bickel PE, Stefanovic-Racic M, Toledo FG, Goodpaster BH (2010) Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes. Diabetes 60(10):2588–2597

Anastasiou CA, Kavouras SA, Lentzas Y, Gova A, Sidossis LS, Melidonis A (2009a) Diabetes mellitus is associated with increased intramyocellular triglyceride, but not diglyceride, content in obese humans. Metabolism 58(11):1636–1642

Anastasiou CA, Kavouras SA, Lentzas Y, Gova A, Sidossis LS, Melidonis A (2009b) Diabetes mellitus is associated with increased intramyocellular triglyceride, but not diglyceride, content in obese humans. Metabolism 58(11):1636–1642

Bachmann OP, Dahl DB, Brechtel K, Machann J, Haap M, Maier T, Loviscach M, Stumvoll M, Claussen CD, Schick F, Haring HU, Jacob S (2001) Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans. Diabetes 50(11):2579–2584

Badin PM, Louche K, Mairal A, Liebisch G, Schmitz G, Rustan AC, Smith SR, Langin D, Moro C (2012) Altered skeletal muscle lipase expression and activity contribute to insulin resistance in humans. Diabetes 60(6):1734–1742

Bergman BC, Hunerdosse DM, Kerege A, Playdon MC, Perreault L (2012) Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans. Diabetologia 55(4):1140–1150

Björnholm M, Zierath JR (2005) Insulin signal transduction in human skeletal muscle: identifying the defects in Type II diabetes. Biochem Soc Trans 33(2):354–357

Boni LT, Rando RR (1985) The nature of protein kinase C activation by physically defined phospholipid vesicles and diacylglycerols. J Biol Chem 260(19):10819–10825

Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV (1993) The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. New Engl J Med 328(4):238–244

Chavez JA, Summers SA (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(2):101–109

Chavez FP, Ryan J, Lluch-Cota SE, Ñiquen M (2003) From anchovies to sardines and back: multidecadal change in the Pacific Ocean. Science 299(5604):217–221

Chen HC, Smith SJ, Ladha Z, Jensen DR, Ferreira LD, Pulawa LK, McGuire JG, Pitas RE, Eckel RH, Farese RV (2002) Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Investig 109(8):1049–1055

Chen HC, Rao M, Sajan MP, Standaert M, Kanoh Y, Miura A, Farese RV, Farese RV (2004) Role of adipocyte-derived factors in enhancing insulin signaling in skeletal muscle and white adipose tissue of mice lacking Acyl CoA: diacylglycerol acyltransferase 1. Diabetes 53(6):1445–1451

Chibalin AV, Leng Y, Vieira E, Krook A, Bjornholm M, Long YC, Kotova O, Zhong Z, Sakane F, Steiler T, Nylen C, Wang J, Laakso M, Topham MK, Gilbert M, Wallberg-Henriksson H, Zierath JR (2008) Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance. Cell 132(3):375–386

Chow L, From A, Seaquist E (2012) Skeletal muscle insulin resistance: the interplay of local lipid excess and mitochondrial dysfunction. Meta Clin Exp 59(1):70–85

Coen PM, Goodpaster BH (2012) Role of intramyocellular lipids in human health. Trends Endocrinol Metab 23(8):391–398

Coen PM, Dube JJ, Amati F, Stefanovic-Racic M, Ferrell RE, Toledo FG, Goodpaster BH (2010a) Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes 59(1):80–88

Coen PM, Dubé JJ, Amati F, Stefanovic-Racic M, Ferrell RE, Toledo FG, Goodpaster BH (2010b) Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes 59(1):80–88

Coll T, Eyre E, Rodriguez-Calvo R, Palomer X, Sanchez RM, Merlos M, Laguna JC, Vazquez-Carrera M (2008a) Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. J Biol Chem 283(17):11107–11116

Coll T, Eyre E, Rodriguez-Calvo R, Palomer X, Sanchez RM, Merlos M, Laguna JC, Vazquez-Carrera M (2008b) Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. J Biol Chem 283(17):11107–11116

Corcoran MP, Lamon-Fava S, Fielding RA (2007) Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise. Am J Clin Nutr 85(3):662–677

Denton RM, Randle PJ (1967) Concentrations of glycerides and phospholipids in rat heart and gastrocnemius muscles—effects of alloxan-diabetes and perfusion. Biochem J 104(2):416–419

Dimopoulos N, Watson M, Sakamoto K, Hundal H (2006) Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells. Biochem J 399:473–481

Dube JJ, Amati F, Toledo FG, Stefanovic-Racic M, Rossi A, Coen P, Goodpaster BH (2011) Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia 54(5):1147–1156

Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365(9468):1415–1428

Erion DM, Shulman GI (2010) Diacylglycerol-mediated insulin resistance. Nat Med 16(4):400–402

Fleischman A, Kron M, Systrom DM, Hrovat M, Grinspoon SK (2009) Mitochondrial function and insulin resistance in overweight and normal-weight children. J Clin Endocrinol Metab 94(12):4923–4930

Fridlyand LE, Philipson LH (2006) Reactive species and early manifestation of insulin resistance in type 2 diabetes. Diabetes Obes Metab 8(2):136–145

Fritz IB, Davis DG, Holtrop RH, Dundee H (1958) Fatty acid oxidation by skeletal muscle during rest and activity. Am J Phys Leg Content 194(2):379–386

Gao Z, Wang Z, Zhang X, Butler AA, Zuberi A, Gawronska-Kozak B, Lefevre M, York D, Ravussin E, Berthoud HR, McGuinness O, Cefalu WT, Ye J (2007) Inactivation of PKC theta leads to increased susceptibility to obesity and dietary insulin resistance in mice. Am J Phys Endocrinol Metab 292(1):E84–E91

Gao D, Griffiths HR, Bailey CJ (2009) Oleate protects against palmitate-induced insulin resistance in L6 myotubes. Br J Nutr 102(11):1557–1563

Goodpaster BH, He J, Watkins S, Kelley DE (2001) Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 86(12):5755–5761

Hees AM, Jans A, Hul GB, Roche HM, Saris WH, Blaak EE (2001) Skeletal muscle fatty acid handling in insulin resistant men. Obesity 19(7):1350–1359

Helge JW, Dobrzyn A, Saltin B, Gorski J (2004) Exercise and training effects on ceramide metabolism in human skeletal muscle. Exp Phys 89(1):119–127

Hernandez-Alvarez MI, Thabit H, Burns N, Shah S, Brema I, Hatunic M, Finucane F, Liesa M, Chiellini C, Naon D, Zorzano A, Nolan JJ (2010) Subjects with early-onset type 2 diabetes show defective activation of the skeletal muscle PGC-1α/Mitofusin-2 regulatory pathway in response to physical activity. Diabetes Care 33(3):645–651

Himwich HE, Rose MI (1926) The respiratory quotient of exercising muscle. Exp Biol Med 24(2):169–170

Holland WL, Bikman BT, Wang LP, Yuguang G, Sargent KM, Bulchand S, Knotts TA, Shui G, Clegg DJ, Wenk MR, Pagliassotti MJ, Scherer PE, Summers SA (2012) Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Investig 121(5):1858–1870

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 Ikappa B-alpha. Diabetes 51(7):2005–2011

Jacob S, Machann J, Rett K, Brechtel K, Volk A, Renn W, Maerker E, Matthaei S, Schick F, Claussen CD (1998) Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes 48(5):1113–1119

James DE, Jenkins AB, Kraegen EW (1985) Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats. Am J Phys Endocrinol Metab 248(5):E567–E574

Jimenez-Caballero PE, Mollejo-Villanueva M, Alvarez-Tejerina A (2008) Mitochondrial encephalopathy due to complex I deficiency. Brain tissue biopsy findings and clinical course following pharmacological. Revi de neur 47(1):27–30

Kelley DE, He J, Menshikova EV, Ritov VB (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51(10):2944–2950

Kern M, Wells JA, Stephens JM, Elton CW, Friedman JE, Tapscott EB, Pekala PH, Dohm GL (1990) Insulin responsiveness in skeletal muscle is determined by glucose transporter [Glut4] protein level. Biochem J 270:397–400

Kim JK, Fillmore JJ, Sunshine MJ, Albrecht B, Higashimori T, Kim DW, Liu ZX, Soos TJ, Cline GW, O’Brien WR, Littman DR, Shulman GI (2004) PKC-theta knockout mice are protected from fat-induced insulin resistance. J Clin Investig 114(6):823–827

Kirwan JP (2013) Plasma ceramides target skeletal muscle in type 2 diabetes. Diabetes 62(2):352–354

Krogh A, Lindhard J (1920) The relative value of fat and carbohydrate as sources of muscular energy: with appendices on the correlation between standard metabolism and the respiratory quotient during rest and work. Biochem J 14(3–4):290

Lee JS, Pinnamaneni SK, Eo SJ, Cho IH, Pyo JH, Kim CK, Sinclair AJ, Febbraio MA, Watt MJ (2006) Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol 100(5):1467–1474

Levin MC, Monetti M, Watt MJ, Sajan MP, Stevens RD, Bain JR, Newgard CB, Farese RV, Farese RV (2007) Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic [type II] muscle. Am J Phys Endocrinol Metab 293(6):E1772–E1781

Listenberger LL, Han X, Lewis SE, Cases S, Farese RV, Ory DS, Schaffer JE (2003) Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci USA 100(6):3077–3082

Liu L, Zhang Y, Chen N, Shi X, Tsang B, Yu YH (2007) Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J Clin Investig 117(6):1679–1689

Lowell BB, Shulman GI (2005) Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. Diabetes 307(10):384–387

Marshall J, Bessesen D, Hamman R (1997) High saturated fat and low starch and fibre are associated with hyperinsulinaemia in a non-diabetic population: the San Luis Valley Diabetes Study. Diabetologia 40(4):430–438

Meex RC, Schrauwen-Hinderling VB, Moonen-Kornips E, Schaart G, Mensink M, Phielix E, van de Weijer T, Sels JP, Schrauwen P, Hesselink MK (2010) Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity. Diabetes 59(3):572–579

Moro C, Galgani JE, Luu L, Pasarica M, Mairal A, Bajpeyi S, Schmitz G, Langin D, Liebisch G, Smith SR (2009) Influence of gender, obesity, and muscle lipase activity on intramyocellular lipids in sedentary individuals. J Clin Endocrinol Metab 94(9):3440–3447

Pan DA, Lillioja S, Milner MR, Kriketos AD, Baur LA, Bogardus C, Storlien LH (1995) Skeletal muscle membrane lipid composition is related to adiposity and insulin action. J Clin Investig 96(6):2802–2808

Peng G, Li L, Liu Y, Pu J, Zhang S, Yu J, Zhao J, Liu P (2012) Oleate blocks palmitate-induced abnormal lipid distribution, endoplasmic reticulum expansion and stress, and insulin resistance in skeletal muscle. Endocrinology 152(6):2206–2218

Pette D, Peuker H, Staron R (1999) The impact of biochemical methods for single muscle fibre analysis. Acta Phys Scand 166(4):261–277

Pickersgill L, Litherland GJ, Greenberg AS, Walker M, Yeaman SJ (2007) Key role for ceramides in mediating insulin resistance in human muscle cells. J Biol Chem 282(17):12583–12589

Raben A, Mygind E, Astrup A (1998) Lower activity of oxidative key enzymes and smaller fiber areas in skeletal muscle of postobese women. Am J Phys Endocrinol Metab 275(3):E487–E494

Randle P, Garland P, Hales C, Newsholme E (1963) The glucose fatty-acid cycle its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 281(7285):785–789

Russell AP, Gastaldi G, Bobbioni-Harsch E, Arboit P, Gobelet C, Deriaz O, Golay A, Witztum JL, Giacobino JP (2003) Lipid peroxidation in skeletal muscle of obese as compared to endurance-trained humans: a case of good vs. bad lipids? FEBS 551(1):104–106

Saltiel AR (2000) Series introduction: the molecular and physiological basis of insulin resistance: emerging implications for metabolic and cardiovascular diseases. J Clin Investig 106(2):163–164

Salvado L, Coll T, Gomez-Foix AM, Salmeron E, Barroso E, Palomer X, Vazquez-Carrera M (2013) Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism. Diabetologia 56(6):1372–1382

Samuel VT, Shulman GI (2012) Mechanisms for insulin resistance: common threads and missing links. Cell 148(5):852–871

Sawada K, Kawabata K, Yamashita T, Kawasaki K, Yamamoto N, Ashida H (2012) Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells. Lipids Health Dis 11:36

Schenk S, Horowitz JF (2007) Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J Clin Investig 117(6):1690–1698

Schmitz-Peiffer C, Craig DL, Biden TJ (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(34):24202–24210

Schrauwen P, Hesselink MK (2004) Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. Diabetes 53(6):1412–1417

Schrauwen P, Schrauwen-Hinderling V, Hoeks J, Hesselink ML (2010) Mitochondrial dysfunction and lipotoxicity. Biochem Biophys Acta 1801(3):266–271

Serra C, Federici M, Buongiorno A, Senni MI, Morelli S, Segratella E, Pascuccio M, Tiveron C, Mattei E, Tatangelo L, Lauro R, Molinaro M, Giaccari A, Bouche M (2003) Transgenic mice with dominant negative PKC-theta in skeletal muscle: a new model of insulin resistance and obesity. J Cell Phys 196(1):89–97

Shaw CS, Shepherd SO, Wagenmakers AJ, Hansen D, Dendale P, van Loon LJ (2012) Prolonged exercise training increases intramuscular lipid content and perilipin 2 expression in type I muscle fibers of patients with type 2 diabetes. Am J Phys Endocrinol Metab 303(9):E1158–E1165

Skovbro M, Baranowski M, Skov-Jensen C, Flint A, Dela F, Gorski J, Helge JW (2008) Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity. Diabetologia 51(7):1253–1260

Smith ME, Tippetts TS, Brassfield ES, Tucker BJ, Ockey A, Swensen AC, Anthonymuthu TS, Washburn TS, Kane DA, Prince JT, and Bikman BT (2013) Mitochondrial fission mediates ceramide-induced metabolic disruption in skeletal muscle. Biochem J:135–140

Soriguer F, Esteva I, Rojo-Martinez G, de Adana MR, Dobarganes M, Garcia-Almeida J, Tinahones F, Beltran M, Gonzalez-Romero S, Olveira G (2004) Oleic acid from cooking oils is associated with lower insulin resistance in the general population [Pizarra study]. Eur J Endocrinol 150(1):33–39

Storlien LH, Jenkins AB, Chisholm DJ, Pascoe WS, Khouri S, Kraegen EW (1991) Influence of dietary fat composition on development of insulin resistance in rats: relationship to muscle triglyceride and ω-3 fatty acids in muscle phospholipid. Diabetes 40(2):280–289

Storlien L, Pan D, Kriketos A, O’Connor J, Caterson I, Cooney G, Jenkins A, Baur L (1996) Skeletal muscle membrane lipids and insulin resistance. Lipids 31(1):S261–S265

Storlien LH, Hulbert AJ, Else PL (1998) Polyunsaturated fatty acids, membrane function and metabolic diseases such as diabetes and obesity. Curr Opin Clin Nutr Metab Care 1(6):559–563

Storlien LH, Higgins J, Thomas T, Brown MA, Wang H, Huang XF, Else P (2002) Diet composition and insulin action in animal models. Br J Nutr 83(s1):S85–S90

Stratford S, Hoehn KL, Liu F, Summers SA (2004) Regulation of insulin action by ceramide dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. J Biol Chem 279(35):36608–36615

Thrush AB, Harasim E, Chabowski A, Gulli R, Stefanyk L, Dyck DJ (2010) A single prior bout of exercise protects against palmitate-induced insulin resistance despite an increase in total ceramide content. Am J Phys Regu Integr Comp Phys 300(5):R1200–R1208

Timmers S, Schrauwen P, de Vogel J (2008) Muscular diacylglycerol metabolism and insulin resistance. Physiol Behav 94(2):242–251

Timmers S, de Vogel-van den Bosch J, Hesselink MK, van Beurden D, Schaart G, Ferraz MJ, Losen M, Martinez-Martinez P, De Baets MH, Aerts JM (2010) Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. Plos one 6(1):14500–14503

Turinsky J, O’Sullivan DM, Bayly BP (1990) 1, 2-Diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo. J Biol Chem 265(28):16880–16885

Ussher JR, Koves TR, Cadete VJ, Zhang L, Jaswal JS, Swyrd SJ, Lopaschuk DG, Proctor SD, Keung W, Muoio DM, Lopaschuk GD (2010) Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption. Diabetes 59(10):2453–2464

Van Loon LJ (2004) Use of intramuscular triacylglycerol as a substrate source during exercise in humans. J Appl Phys 97(4):1170–1187

Watt MJ (2009) Storing up trouble: does accumulation of intramyocellular triglyceride protect skeletal muscle from insulin resistance. Clin Exp Pharmcol Phys 36(1):5–11

White LJ, Ferguson MA, McCoy SC, Kim H (2003) Intramyocellular lipid changes in men and women during aerobic exercise: a [1]H-magnetic resonance spectroscopy study. J Clin Endocrinol Metab 88(12):5638–5643

Yuzefovych L, Wilson G, Rachek L (2010) Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress. Am J Phys Endocinol Metab 299(E):1096–1105

Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, Madeo G (2012) Fat signals-lipases and lipolysis in lipid metabolism and signaling. Cell Metab 15(3):279–291