The journal of nutrition, health & aging

, Volume 19, Issue 4, pp 389–396 | Cite as

Skeletal muscle ceramide species in men with abdominal obesity

  • Maria Pia de la MazaEmail author
  • J. M. Rodriguez
  • S. Hirsch
  • L. Leiva
  • G. Barrera
  • D. Bunout


Introduction: Background

Obesity is a risk factor for diabetes and its consequences, including accelerated ageing and mortality. The underlying factor could be accumulation of certain lipid moieties, such as ceramides (CER) and diacylgycerol (DAG) within muscle tissue, which are known to promote insulin resistance (IR), induce inflammation and oxidative injury, ultimately altering muscle function.


First, to study the relationship between body composition and age (independent variables) with skeletal muscle accumulation of lipid species, oxidative injury and strength. Second, to analyze the relationship between muscle tissue metabolites and insulin resistance, inflammation and lymphocyte telomere length, the latter as an indicator of ageing.


The sample included 56 healthy sedentary males, scheduled for inguinal hernia surgery, aged 27 to 80 y. Each individual was subject to anthropometric measurements, body composition assessment through radiologic densitometry (DEXA), measurement of handgrip and quadriceps strength, serum biochemical parameters (lipoproteins, creatinine, high sensitivity C reactive protein [hsCRP], fasting and post glucose insulin and glucose concentrations for calculation of IR through the Matsuda and HOMA-IR indexes), and extraction of peripheral leukocytes for measurement of telomere length. During the surgical procedure, a sample of muscle tissue was obtained (anterior abdominal oblique) in order to measure CER and DAG (and sub species according to chain length and saturation) by mass spectrometry, 4 hydroxy-2-nonenal adducts (4-HNE) using electron microscopy immunohistochemistry, and carboxymethyl-lisine (CML) by immunohistochemistry, the latter as indicators of oxidative stress (OS).Results: Body mass index (BMI) of twenty six individuals was > 25 k/m2, while BMI of 7 was > 30 k/m2. Overweight/obese individuals, did not exhibit differences in skeletal muscle lipid metabolites, however total CER and specific long chain CER sub-species (20 and 22 carbon) increased significantly among individuals with a central fat distribution (n = 14) as well as in glucose intolerant subjects (n =23). A negative association was found between mononuclear leukocyte telomere length and 20 and 22 carbon CER (rho = − 0.4 and −0.5 0 p < 0.05). Muscle strength was not associated with any of the measured muscle metabolites or markers of OS. A multiple regression analysis accepted central abdominal fat and telomere length as significant predictors of CER (R2 = 0.28).


An association was found between accumulation of specific ceramide species in muscle tissue and abdominal obesity, glucose intolerance and shortening of leukocyte telomeres, although not with muscle oxidative injury or dysfunction.

Key words

Ceramide DAG intramyocellular obesity ageing 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Timmers S, Schrauwen P, de Vogel J. Muscular diacylglycerol metabolism and insulin resistance. Physiol Behav 2008;94:242–51.CrossRefPubMedGoogle Scholar
  2. 2.
    Eckardt K, Taube A, Eckel J. Obesity-associated insulin resistance in skeletal muscle: Role of lipid accumulation and physical inactivity. Rev Endocr Metab Disord 2011;12:163–172.CrossRefPubMedGoogle Scholar
  3. 3.
    Medina-Gomez G, Gray S, Vidal-Puig A. Adipogenesis and lipotoxicity: role of peroxisome proliferator activated receptor gamma (PPAR gamma? and PPAR gamma? coactivator-1 (PGC1). Public Health Nutr 2007;10:1132–1137.CrossRefPubMedGoogle Scholar
  4. 4.
    Hwang JH, Stein DT, Barzilai N, Cui MH, Tonelli J, Kishore P, Hawkins M. Increased intrahepatic triglyceride is associated with peripheral insulin resistance: in vivo MR imaging and spectroscopy studies. Am J Physiol Endocrinol Metab 2007;293:E1663–9.CrossRefGoogle Scholar
  5. 5.
    Schrauwen-Hinderling VB, Schrauwen P, Hesselink MK, van Engelshoven JM, Nicolay K, Saris WH, Kessels AG, Kooi ME. The increase in intramyocellular lipid content is a very early response to training. J Clin Endocrinol Metab 2003;88:1610–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 2001;86:5755–61.CrossRefPubMedGoogle Scholar
  7. 7.
    Bosma M, Kersten S, Hesselink MKC, Schrauwen P. Re-evaluating lipotoxic triggers in skeletal muscle: Relating intramyocellular lipid metabolism to insulin sensitivity. ProgLip Res 2012;51:36–49.Google Scholar
  8. 8.
    Brands M, Van Raalte DH, Ferraz MJ, Sauerwein HP, Verhoeven AJ, Aerts JMFG, Diamant M, Serlie MJ. No Difference in Glycosphingolipid Metabolism and Mitochondrial Function in Glucocorticoid-Induced Insulin Resistance in Healthy Men. J Clin Endocrinol Metab 2013;98:1219–1225.CrossRefPubMedGoogle Scholar
  9. 9.
    Saddoughi SA, Song P, Ogretmen B. Roles of Bioactive Sphingolipids in Cancer Biology and Therapeutics. Subcell Biochem 2008;49:413–440PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Coen PM, Dubé JJ, Amati F, Stefanovic-Racic M, Ferrell RE, Toledo FGS, Goodpaster BH. Insulin Resistance Is Associated With Higher Intramyocellular Triglycerides in Type I but Not Type II Myocytes Concomitant With Higher Ceramide Content. Diabetes 2010;59:80–88.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Adams JM, Pratipanawatr T, Berria R, Wang E, DeFronzo RA, Sullards MC, Mandarino LJ. Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 2004;53:25–31.CrossRefPubMedGoogle Scholar
  12. 12.
    Straczkowski M, Kowalska I, Baranowski M, Nikolajuk A, Otziomek E, Zabielski P, Adamska A, Blachnio A, Gorski J, Gorska M. Increased skeletal muscle ceramide level in men at risk of developing type 2 diabetes. Diabetologia 2007;50:2366–2373.CrossRefPubMedGoogle Scholar
  13. 13.
    Boon J, Hoy AJ, Stark R, Brown RD, Meex RC, Henstridge DC, Schenk S, Meikle PJ, Horowitz JF, Kingwell BA, Bruce CR, Watt MJ. Ceramides Contained in LDL Are Elevated in Type 2 Diabetes and Promote Inflammation and Skeletal Muscle Insulin Resistance. Diabetes 2013;62:401–410.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Haus JM, Kashyap SR, Kasumov T, Zhang R, Kelly KR, DeFronzo RA, Kirwan JP. Plasma Ceramides Are Elevated in Obese Subjects With Type 2 Diabetes and Correlate With the Severity of Insulin Resistance. Diabetes 2009;58:337–343.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Skovbro M, Baranowski M, Skov-Jensen C, Flint A, Dela F, Gorski J, Helge JW. Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity. Diabetologia 2008;51:1253–1260.CrossRefPubMedGoogle Scholar
  16. 16.
    Straczkowski M, Kowalska I. The Role of Skeletal Muscle Sphingolipids in the Development of Insulin Resistance. Rev Diabet Stud 2008;5:13–24PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Yang G, Badeanlou L, Bielawski J, Roberts AJ, Yusuf A, Samad H, Samad F. Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome. Am J Physiol Endocrinol Metab 2009;297:E211–E224.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Ussher JR, Koves TR, Cadete VJJ, Zhang L, Jaswal JS, Swyrd SJ, Lopaschuk DG, Proctor SD, Keung W, Muoio DM, Lopaschuk GD. Inhibition of De Novo Ceramide Synthesis Reverses Diet-Induced Insulin Resistance and Enhances Whole-Body Oxygen Consumption. Diabetes 2010;59:2453–2464.PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Bruce CR, Thrush AB, Mertz VA, Bezaire V, Chabowski A, Heigenhauser GJ, Dyck DJ. Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am J Physiol Endocrinol Metab 2006;291:E99–E107.CrossRefPubMedGoogle Scholar
  20. 20.
    Dube JJ, Amati F, Stefanovic-Racic M, Toledo FG, Sauers SE, Goodpaster BH. Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete’s paradox revisited. Am J Physiol Endocrinol Metab 2008;294:E882–E888.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 2002;51:2005–11.CrossRefPubMedGoogle Scholar
  22. 22.
    De la Maza MP, Olivares D, Hirsch S, Sierralta W, Gattas V, Barrera G, Bunout D, Leiva L, Fernandez M. Weight increase and overweight are associated with DNA oxidative damage in skeletal muscle. Clin Nutr 2006;25:968–76.CrossRefPubMedGoogle Scholar
  23. 23.
    De la Maza MP, Uribarri J, Olivares D, Hirsch S, Leiva L, Barrera G, Bunout D. Weight Increase Is Associated with Skeletal Muscle Immunostaining for Advanced Glycation End Products, Receptor for Advanced Glycation End Products, and Oxidation Injury. Rejuvenation Res 2008;11:1041–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Zainal TA, Oberley TD, Allison DB, Szweda LI, Weindruch R. Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle. FASEB J.; 2000;14:1825–36.CrossRefPubMedGoogle Scholar
  25. 25.
    Vlassara H, Cai W, Chen X, Serrano EJ, Shobha MS, Uribarri J, Woodward M, Striker GE. Managing chronic inflammation in the aging diabetic patient with CKD by diet or sevelamer carbonate: a modern paradigm shift. J Gerontol A BiolSci Med Sci. 2012;67:1410–6.CrossRefGoogle Scholar
  26. 26.
    Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ. Abdominal fat and insulin resistance in normal and overweight women. Diabetes 1996;45:633–638.CrossRefPubMedGoogle Scholar
  27. 27.
    Stern SE, Williams K, Ferrannini E, DeFronzo RA, Bogardus C, Stern MP. Identification of individuals with insulin resistance using routine clinical measurements. Diabetes 2005;54:333–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462–70.CrossRefPubMedGoogle Scholar
  29. 29.
    Bunout D, Backhouse C, Leiva L, Barrera G, Sierralta W, de la Maza MP, Hirsch S. Relationship between protein and mitochondrial DNA oxidative injury and telomere length and muscle loss in healthy elderly subjects. Arch Gerontol Geriatr 2009;48:335–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Cawthon R.M. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002;30:e47CrossRefGoogle Scholar
  31. 31.
    Bunout D, Barrera G, Leiva L, Gattas V, de la Maza MP, Avendaño M, Hirsch S. Effects of vitamin D supplementation and exercise training on physical performance in Chilean vitamin D deficient elderly subjects. Exp Gerontol 2006;41:746–52CrossRefPubMedGoogle Scholar
  32. 32.
    Mielke MM, Bandaru VV, Haughey NJ, Xia J, Fried LP, Yasar S, Albert M, Varma V, Harris G, Schneider EB, Rabins PV, Bandeen-Roche K, Lyketsos CG, Carlson MC. Serum ceramides increase the risk of Alzheimer disease: the Women’s Health and Aging Study II. Neurology 2012;79:633–41.PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Varman TS, Shulman GI. Mechanisms for Insulin Resistance: Common Threads and Missing Links. Cell 2012;148:852–871.CrossRefGoogle Scholar
  34. 34.
    Cree MG, Newcomer BR, Katsanos CS, Sheffield-Moore M, Chinkes D, Aarsland A, Urban R, Wolfe RR. Intramuscular and liver triglycerides are increased in the elderly. J Clin Endocrinol Metab 2004;89:3864–3871.CrossRefPubMedGoogle Scholar
  35. 35.
    Sinha R, Dufour S, Petersen KF, LeBon V, Enoksson S, Ma YZ, Savoye M, Rothman DL, Shulman GI, Caprio S. Assessment of Skeletal Muscle Triglyceride Content by 1H Nuclear Magnetic Resonance Spectroscopy in Lean and Obese Adolescents. Relationships to Insulin Sensitivity, Total Body Fat, and Central Adiposity. Diabetes 2002;51:1022–1027.PubMedGoogle Scholar
  36. 36.
    Bosma M, Kersten S, Hesselink MKC, Schrauwen P (2012) Re-evaluating lipotoxic triggers in skeletal muscle: Relating intramyocellular lipid metabolism to insulin sensitivity. Progress in Lipid Research 2012;51:36–49.CrossRefPubMedGoogle Scholar
  37. 37.
    Moro C, Galgani JE, Lu LC, Pasarica M, Mairal A, Bajpeyi S, Schmitz G, Langin D, Liebisch G, Smith SR. Influence of Gender, Obesity, and Muscle Lipase Activity on Intramyocellular Lipids in Sedentary Individuals. J Clin Endocrinol Metab 2009;94:3440–7.PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic Differences in Hepatic Steatosis: An insulin resistance paradox? Hepatology 2009;49:791–801.PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Thrush AB, Brindley DN, Chabowski A, Heigenhauser GJ, Dyck DJ. Skeletal muscle lipogenic protein expression is not different between lean and obese individuals: a potential factor in ceramide accumulation. J Clin Endocrinol Metab 2009;94:5053–61.CrossRefPubMedGoogle Scholar
  40. 40.
    Stults-Kolehmainen MA, Stanforth PR, Bartholomew JB, Lu T, Abolt CJ, Sinha R. DXA estimates of fat in abdominal, trunk and hip regions varies by ethnicity in men. Nutr Diabetes 2013;18:e64.CrossRefGoogle Scholar
  41. 41.
    Gaster M, Rustan AC, Beck-Nielsen H. Differential utilization of saturated palmitate and unsaturated oleate: evidence from cultured myotubes. Diabetes 2005;54:648–656.CrossRefPubMedGoogle Scholar
  42. 42.
    Rivas DA, Morris EP, Haran PH, Pasha EP, Da Silva Morais M, Dolnikowski GG, Phillips EM, Fielding RA. Increased ceramide content and NFB signaling may contribute to the attenuation of anabolic signaling after resistance exercise in aged males. J Appl Physiol 2012;113:1727–1736.PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Galgani JE, Vasquez K, Watkins G, Dupuy A, Bertrand-Michel J, Levade T, Moro C. Enhanced Skeletal Muscle Lipid Oxidative Efficiency in Insulin-Resistant vs Insulin-Sensitive Nondiabetic, Nonobese Humans. J Clin Endocrinol Metab 2013;98:E646–E653.CrossRefPubMedGoogle Scholar
  44. 44.
    Coen PM, Goodpaster BH. Role of intramyocelluar lipids in human health. Trends in Endocrinology and Metabolism 2012;23:391–398CrossRefPubMedGoogle Scholar
  45. 45.
    Powers SK, Smuder AJ, Judge AR. Oxidative stress and disuse muscle atrophy: cause or consequence? Curr Opin Clin Nutr Metab Care 2012;15:240–5.PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Ahmad S, Heraclides A, Sun Q, Elgzyri T, Ronn T, Ling C, Isomaa B, Eriksson KF, Groop L, Franks PW, Hansson O. Telomere length in blood and skeletal muscle in relation to measures of glycaemia and insulinaemia. Diabet. Med 2012;29:e377–e381.PubMedCentralCrossRefPubMedGoogle Scholar
  47. 47.
    Zhao J, Zhu Y, Lin J. Short leukocyte telomere length predicts risk of diabetes in American Indians: the Strong Heart Family Study. Diabetes 2014;63:354–62.PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Blachnio-Zabielska AU, Koutsaria C, Tchkoniab T, Jensena MD. Sphingolipid content of human adipose tissue: relationship to adiponectin and insulin resistance. Obesity (Silver Spring) 2012;20: 2341–2347.CrossRefGoogle Scholar
  49. 49.
    Bergman BC, Hunerdosse DM, Kerege A, Playdon MC, Perreault L. Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans. Diabetologia 2012;55:1140–1150.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Serdi and Springer-Verlag France 2014

Authors and Affiliations

  • Maria Pia de la Maza
    • 1
    Email author
  • J. M. Rodriguez
    • 1
  • S. Hirsch
    • 1
  • L. Leiva
    • 1
  • G. Barrera
    • 1
  • D. Bunout
    • 1
  1. 1.Institute of Nutrition and Food TechnologyUniversity of ChileSantiagoChile

Personalised recommendations