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

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. © 2011 Springer-Verlag.