Table 1.
Characteristics of the study groups.
As expected, BMI, plasma glucose, triglycerides, HDL-cholesterol, VLDL-cholesterol and sCD163 are significantly different between healthy controls and MetS patients.
Fig 1.
Plasma levels of CE, PC, LPC, SM (A), and PE, PE P, PI, and Cer (B) from controls and patient groups.
From all the major lipid classes analyzed only changes in LPC levels reached significance in MetS patients ((n = 12 (Control), n = 19 (Risk), and n = 33 (MetS)) (A). Lipid species were analyzed either by LC-MS/MS or ESI-MS/MS, as described in Methods, and are expressed in μmol/l of plasma. Data presented as mean ± SEM. * p<0.05, statistically different with respect to control.
Fig 2.
Plasma levels of SPC and S1P from controls and patient groups.
(A): Total SPC; (B): SPC-species; (C): S1P. SPC levels were significantly increased in MS patients but not in those at risk for diabesity (A). SPC increase was due to an increase in all three main subspecies (B). MetS patients have significant lower levels of S1P (C). S1P and SPC-species (n = 8 (Control), n = 8 (Risk), and n = 9 (MetS) were analyzed by LC-MS/MS and are expressed in μmol/l of plasma. Data presented as mean ± SEM. * p<0.05, **p<0.005, ***p<0.0005 statistically different with respect to control.
Fig 3.
Plasma LPC species levels in controls and patient groups.
A significant decrease in specific LPC species plasma levels was observed in MetS patients but not in patients at risk for diabesity ((n = 12 (Control), n = 19 (Risk), and n = 33 (MetS)). LPC-species were analyzed by ESI-MS/MS and are expressed in μmol/l of plasma. Data presented as mean ± SEM. * p<0.05, statistically different with respect to control.
Table 2.
Correlation between BMI, sCD163 and triglycerides with total and individual SPC species.
Table 3.
Correlation between BMI and sCD163 with S1P.
Table 4.
Correlation between BMI and sCD163 total and individual LPC species.
Fig 4.
Hypothetical scheme depicting SPC and S1P synthesis.
Ceramides (Cer) are generated from the sphingomyelinase pathway and other pathways such as the salvage pathway and the de novo synthesis pathway (not shown in this scheme). Sphingosine (SPH) which can be formed from the degradation and recycling of complex sphingolipids and glycosphingolipids in an acidic environment (salvage pathway) may also contribute to Cer metabolism. SPH is phosphorylated by SPH kinase to sphingosine-1-phosphate (S1P), a bioactive lipid intermediates with several effects. In addition to Cer, SPC is another biologically active lipid metabolite generated from sphingomyelin (SM) under the action of a SM-deacylase. Secreted SPC is likely a substrate for autotaxin (ATX), an exoenzyme with lysophospholipase D activity, which leads to S1P generation. Alternatively, S1P can be converted from SPC by ectonucleotide pyrophosphatase/phosphodiesterases (ENPPs). SPC and S1P can both induce their effects through binding to G-protein coupled receptors present on different cell types. It cannot be excluded that an intracellular SPC—> S1P conversion also occurs by a yet unidentified SPC-ase, and not SPC but rather S1P is secreted from cells predominantly. Extracellular S1P might be converted back to SPC through not yet identified enzyme(s). Substantial amounts of extracellular SPC and S1P are loaded to preβ-HDL particles and therefore they may contribute to the composition and/or maturation of α-HDL lipoproteins. UC: unesterified cholesterol, PC: phosphatidylcholine, LPC: lysophosphatidylcholine, PM: plasma membrane.