Similarities and differences in lipidomics profiles among healthy monozygotic twin pairs.

Differences in genetic background and/or environmental exposure among individuals are expected to give rise to differences in measurable characteristics, or phenotypes. Consequently, genetic resemblance and similarities in environment should manifest as similarities in phenotypes. The metabolome reflects many of the system properties, and is therefore an important part of the phenotype. Nevertheless, it has not yet been examined to what extent individuals sharing part of their genome and/or environment indeed have similar metabolomes. Here we present the results of hierarchical clustering of blood plasma lipid profile data obtained by liquid chromatographymass spectrometry from 23 healthy, 18-year-old twin pairs, of which 21 pairs were monozygotic, and 8 of their siblings. For 13 monozygotic twin pairs, within-pair similarities in relative concentrations of the detected lipids were indeed larger than the similarities with any other study participant. We demonstrate such high coclustering to be unexpected on basis of chance. The similarities between dizygotic twins and between nontwin siblings, as well as between nonfamilial participants, were less pronounced. In a number of twin pairs, within-pair dissimilarity of lipid profiles positively correlated with increased blood plasma concentrations of C-reactive protein in one twin. In conclusion, this study demonstrates that in healthy individuals, the individual genetic background contributes to the blood plasma lipid profile. Furthermore, lipid profiling may prove useful in monitoring health status, for example, in the context of personalized medicine. © 2008 Mary Ann Liebert, Inc. Chemicals / CAS: C-Reactive Protein, 9007-41-4; Lipid

Lipidomics Reveals Multiple Pathway Effects of a Multi-Components Preparation on Lipid Biochemistry in ApoE*3Leiden.CETP Mice

Background: Causes and consequences of the complex changes in lipids occurring in the metabolic syndrome are only partly understood. Several interconnected processes are deteriorating, which implies that multi-target approaches might be more successful than strategies based on a limited number of surrogate markers. Preparations from Chinese Medicine (CM) systems have been handed down with documented clinical features similar as metabolic syndrome, which might help developing new intervention for metabolic syndrome. The progress in systems biology and specific animal models created possibilities to assess the effects of such preparations. Here we report the plasma and liver lipidomics results of the intervention effects of a preparation SUB885C in apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) mice. SUB885C was developed according to the principles of CM for treatment of metabolic syndrome. The cannabinoid receptor type 1 blocker rimonabant was included as a general control for the evaluation of weight and metabolic responses. Methodology/Principal Findings: ApoE*3Leiden.CETP mice with mild hypercholesterolemia were divided into SUB885C-, rimonabant- and non-treated control groups. SUB885C caused no weight loss, but significantly reduced plasma cholesterol (-49%, p <0.001), CETP levels (-31%,

Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: investigating differential effects among statins

Objective: Lipid profiling (lipidomics) may be useful in revealing detailed information with regard to the effects on lipid metabolism, the cardiovascular risk and to differentiate between therapies. The aims of the present study were to: (1) analyze in depth the lipid changes induced by rosuvastatin and atorvastatin at different dosages; (2) compare differences between the two drugs with respect to the lipid profile change; (3) relate the findings with meaningful pathological mechanisms of coronary artery disease. Research design and methods: Liquid chromatography-mass spectrometry was applied to obtain the metabolite profiles of plasma samples taken from a prospectively defined subset (n = 80) of participants in the RADAR study where a randomly assigned treatment with rosuvastatin or atorvastatin in increasing dosages was administered during an 18-week period. Results: A number of sphingomyelins (SPMs) and phosphatidylcholines (PCs) correlate with the different effects of the two statins on the LDL-C/HDL-C ratio. Rosuvastatin increased the plasma concentration of PCs after 6 and 18 weeks, while atorvastatin reduced the plasma concentrations of PCs at both timepoints and dosages (p <0.01 for between-treatment comparison). Both atorvastatin and rosuvastatin lowered plasma SPMs concentrations, but atorvastatin demonstrated a more pronounced effect with the highest dose (p = 0.03). Rosuvastatin resulted in a significantly more effective lowering of the [SPMs/(SPMs + PCs)] ratio than atorvastatin at any close/timepoint (p <0.05), a ratio reported to be of clinical importance in coronary artery disease. Conclusions: The lipidomic technique has revealed that statins are different with regards to the effect on detailed lipid profile. The observed difference in lipids may be connected with different clinical outcomes as suggested by the [SPMs/(SPMs + PCs)] rati

Significantly changed lipids in each lipid class.

<p>Significantly changed lipids in each lipid class.</p

Effects on some lipid parameters of SUB885C and existing drugs in the ApoE^*3Leiden.CETP female mice model.

<p>Basic diet for ApoE*3Leiden.CETP female mice during run-in and study period: Western type diet with 15% w/w fat plus different content of cholesterol.</p><p>NS: no significance.</p><p>*Dependent on different doses of Niacin.</p

Food intake and body weight.

<p>(A) Food intake (per cage) and (B) body weight (per mouse) were recorded and measured at day 0, 2, 3, 4, 9, 11, 14, 21 and 28 for SUB885C-treated mice and control (*<i>p</i><0.05 vs. control).</p

The summary of SUB885C effects.

<p>The effects of SUB885C were illustrated both in vitro and in ApoE*3Leiden.CETP mice with biochemical and lipidomics measurements. The improvement for insulin sensitivity was result from Wang et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030332#pone.0030332-Wang1" target="_blank">[7]</a>.</p