Correlation between BMI and sCD163 total and individual LPC species.

<p>*. Correlation is significant at the 0.05 level (2-tailed), and</p><p>**. Correlation is significant at the 0.01 level (2-tailed).</p><p>Correlation between BMI and sCD163 total and individual LPC species.</p

Characteristics of the study groups.

<p>BMI: Body Mass Index, LDL: low density lipoprotein, HDL: high density lipoprotein, VLDL: very low density lipoprotein.</p><p>*vs. control</p><p>* <i>p<</i>0.05</p><p>** <i>p<</i>0.001</p><p>*** <i>p<</i>0.0001</p><p>≠ vs. risk: ≠ <i>p<</i>0.05</p><p>≠ ≠ ≠ <i>p<</i>0.0001.</p><p>As expected, BMI, plasma glucose, triglycerides, HDL-cholesterol, VLDL-cholesterol and sCD163 are significantly different between healthy controls and MetS patients.</p

Correlation between BMI and sCD163 with S1P.

<p>*. Correlation is significant at the 0.05 level (2-tailed).</p><p>Correlation between BMI and sCD163 with S1P.</p

Plasma LPC species levels in controls and patient groups.

<p>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. * <i>p</i><0.05, statistically different with respect to control.</p

Plasma levels of SPC and S1P from controls and patient groups.

<p>(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. * <i>p</i><0.05, **<i>p</i><0.005, ***<i>p</i><0.0005 statistically different with respect to control.</p

Plasma levels of CE, PC, LPC, SM (A), and PE, PE P, PI, and Cer (B) from controls and patient groups.

<p>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. * <i>p</i><0.05, statistically different with respect to control.</p

Hypothetical scheme depicting SPC and S1P synthesis.

<p>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.</p

Mortality association of PC species (A), LPC species (B) and PC O species (C).

<p>EDTA plasma concentrations were determined by ESI-MS/MS. Species with significant association to CAD and total mortality are shown. Models were adjusted for age, gender, smoking, LDL, HDL, diabetes and hypertension. Bars represent the hazard ratio −1. Positive association with CAD is shown in grey and positive association with total mortality in black. Negative association with CAD is shown by a dashed white bar and negative association with total mortality in white. Species are named according to the number of carbon atoms and degree of desaturation. Besides their association the mean concentration and standard deviation are shown. PC and LPC species were annotated based on assumption of even numbered carbon chains only.</p

Increase of ceramide and decrease of LPC in chronic colitis by transfer of CD4⁺CD62L⁺ cells in RAG-1^−/− mice.

<p>(A,B) Lipid analysis of isolated colonic IEC by tandem mass spectrometry (control n = 3, CD4⁺CD62L⁺ n = 6). (A) Proportion of ceramide and LPC of analysed lipids. (B) Proportion of PC and FC of analysed lipids. (C) Histological score. (*p<0.05)</p

Anthropometric and clinical parameters of the examined cohort.

<p>BMI, body mass index; CAD, coronary artery disease; HDL, high density lipoprotein; LDL, low density lipoprotein.</p