Plasma deoxysphingolipids: a novel class of biomarkers for the metabolic syndrome?

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  • Additional Information
    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0006777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0428 (Electronic) Linking ISSN: 0012186X NLM ISO Abbreviation: Diabetologia Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin Springer Verlag
    • Subject Terms:
      Biomarkers/*blood ; Diabetes Mellitus, Type 2/*blood ; Metabolic Syndrome/*blood ; Serine C-Palmitoyltransferase/*blood ; Sphingolipids/*blood; Aged ; Animals ; Biomarkers/metabolism ; Catalysis ; Cohort Studies ; Diabetes Mellitus, Type 2/diagnosis ; Disease Models, Animal ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Principal Component Analysis ; Rats ; Risk ; Streptozocin/pharmacology
    • Abstract:
      Aims/hypothesis: Sphingolipid synthesis is typically initiated by the conjugation of L-serine and palmitoyl-CoA, a reaction catalysed by serine palmitoyltransferase (SPT). SPT can also metabolise other acyl-CoAs (C(12) to C(18)) and other amino acids such as L-alanine and glycine, giving rise to a spectrum of atypical sphingolipids. Here, we aimed to identify changes in plasma levels of these atypical sphingolipids to explore their potential as biomarkers in the metabolic syndrome and diabetes.
      Methods: We compared the plasma profiles of ten sphingoid bases in healthy individuals with those of patients with the metabolic syndrome but not diabetes, and diabetic patients (n = 25 per group). The results were verified in a streptozotocin (STZ) rat model. Univariate and multivariate statistical analyses were used.
      Results: Deoxysphingolipids (dSLs) were significantly elevated (p = 5 × 10⁻⁶) in patients with the metabolic syndrome (0.11 ± 0.04 μmol/l) compared with controls (0.06 ± 0.02 μmol/l) but did not differ between the metabolic syndrome and diabetes groups. Levels of C(16)-sphingosine-based sphingolipids were significantly lowered in diabetic patients but not in patients with the metabolic syndrome but without diabetes (p = 0.008). Significantly elevated dSL levels were also found in the plasma and liver of STZ rats. A principal component analysis revealed a similar or even closer association of dSLs with diabetes and the metabolic syndrome in comparison with the established biomarkers.
      Conclusions/interpretation: We showed that dSLs are significantly elevated in patients with type 2 diabetes mellitus and non-diabetic metabolic syndrome compared with healthy controls. They may, therefore, be useful novel biomarkers to improve risk prediction and therapy monitoring in these patients.
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    • Accession Number:
      0 (Biomarkers)
      0 (Sphingolipids)
      5W494URQ81 (Streptozocin)
      EC 2.3.1.50 (Serine C-Palmitoyltransferase)
    • Publication Date:
      Date Created: 20111130 Date Completed: 20120619 Latest Revision: 20211021
    • Publication Date:
      20221213
    • Accession Number:
      10.1007/s00125-011-2384-1
    • Accession Number:
      22124606