Skeletal muscle ceramide species in men with abdominal obesity
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 wordsCeramide DAG intramyocellular obesity ageing
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- 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.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
- 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
- 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
- 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
- 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
- 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
- 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
- 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