title: Plasma deoxysphingolipids: a novel class of biomarkers for the metabolic syndrome?
abstract: OBJECTIVE
  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
  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.
authors: Institute for Clinical Chemistry, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors: A
authors: A
authors: Othman
authors: M F
authors: MF
authors: Rütti
authors: D
authors: D
authors: Ernst
authors: C H
authors: CH
authors: Saely
authors: P
authors: P
authors: Rein
authors: H
authors: H
authors: Drexel
authors: C
authors: C
authors: Porretta-Serapiglia
authors: G
authors: G
authors: Lauria
authors: R
authors: R
authors: Bianchi
authors: A
authors: A
authors: von Eckardstein
authors: T
authors: T
authors: Hornemann
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D002384:Catalysis; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D051381:Rats; D012306:Risk; D051102:Serine C-Palmitoyltransferase / Q000097:blood*; D013107:Sphingolipids / Q000097:blood*; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D013107:Sphingolipids; D013311:Streptozocin; D051102:Serine C-Palmitoyltransferase