Plasma ceramides are elevated in female children and adolescents with type 2 diabetes
-
Ximena Lopez
,
Allison B. Goldfine
Abstract
Accumulation of ceramides within tissues induces insulin resistance. Moreover, adiponectin exerts its beneficial metabolic effects at least partially through ceramide catabolism. We hypothesized that specific plasma ceramide subspecies are elevated in obese children and adolescents with type 2 diabetes (T2D), and that they inversely correlate with adiponectin and measures of insulin sensitivity. This was a cross-sectional study. Participants included 14 obese female subjects with T2D, ages 10–17, and 14 lean healthy controls of the same age and gender. Fasting plasma ceramide subspecies were measured by quantitative tandem mass spectrometry. Subjects with T2D had higher concentrations of C22:0 and C20:0 ceramides, with a 2-fold increase in C18:0 ceramide and C24:1 dihydroceramide (p<0.05). C22:0, C20:0 and C18:0 ceramide correlated with decreased adiponectin concentrations, increased HOMA-IR, BMI Z-score, triglyceride and fasting blood glucose concentrations (p<0.05). Plasma levels of C18:0, C20:0 and C22:0 ceramide, as well as C24:1 dihydroceramide, were elevated in obese female children and adolescents with T2D. This may be a reflection of tissue insulin resistance and could be a result of low adiponectin levels.
References
1. Holland WL, Summers SA. Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev 2008;29:381–402.10.1210/er.2007-0025Search in Google Scholar PubMed PubMed Central
2. Adams JM 2nd, Pratipanawatr T, Berria R, Wang E, DeFronzo RA, et al. Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 2004;53:25–31.10.2337/diabetes.53.1.25Search in Google Scholar PubMed
3. Holland WL, Bikman BT, Wang LP, Yuguang G, Sargent KM, et al. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Invest 2011;121:1858–70.10.1172/JCI43378Search in Google Scholar PubMed PubMed Central
4. Schmitz-Peiffer C, Craig DL, Biden TJ. 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 1999;274:24202–10.10.1074/jbc.274.34.24202Search in Google Scholar PubMed
5. Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med 2011;17: 55–63.10.1038/nm.2277Search in Google Scholar PubMed PubMed Central
6. Haus JM, Kashyap SR, Kasumov T, Zhang R, Kelly KR, et al. Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 2009;58:337–43.10.2337/db08-1228Search in Google Scholar PubMed PubMed Central
7. Błachnio-Zabielska AU, Pułka M, Baranowski M, Nikołajuk A, Zabielski P, et al. Ceramide metabolism is affected by obesity and diabetes in human adipose tissue. J Cell Physiol 2012;227:550–7.10.1002/jcp.22745Search in Google Scholar PubMed
8. Majumdar I, Mastrandrea LD. Serum sphingolipids and inflammatory mediators in adolescents at risk for metabolic syndrome. Endocrine 2012;41:442–9.10.1007/s12020-011-9589-4Search in Google Scholar PubMed
9. Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 2007;5:167–79.10.1016/j.cmet.2007.01.002Search in Google Scholar PubMed
10. Boini KM, Zhang C, Xia M, Poklis JL, Li PL. Role of sphingolipid mediator ceramide in obesity and renal injury in mice fed a high-fat diet. J Pharmacol Exp Ther 2010;334:839–46.10.1124/jpet.110.168815Search in Google Scholar PubMed PubMed Central
11. Langeveld M, Aerts JM. Glycosphingolipids and insulin resistance. Prog Lipid Res 2009;48:196–205.10.1016/j.plipres.2009.03.002Search in Google Scholar PubMed
12. Böttner A, Kratzsch J, Müller G, Kapellen TM, Blüher S, et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 2004;89:4053–61.10.1210/jc.2004-0303Search in Google Scholar PubMed
©2013 by Walter de Gruyter Berlin Boston
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