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An update on oxysterol biochemistry: New discoveries in lipidomics.

ABSTRACT: Oxysterols are oxidised derivatives of cholesterol or its precursors post lanosterol. They are intermediates in the biosynthesis of bile acids, steroid hormones and 1,25-dihydroxyvitamin D3. Although often considered as metabolic intermediates there is a growing body of evidence that many oxysterols are bioactive and their absence or excess may be part of the cause of a disease phenotype. Using global lipidomics approaches oxysterols are underrepresented encouraging the development of targeted approaches. In this article, we discuss recent discoveries important in oxysterol biochemistry and some of the targeted lipidomic approaches used to make these discoveries.

SUBMITTER: Griffiths WJ

PROVIDER: S-EPMC6381446 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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An update on oxysterol biochemistry: New discoveries in lipidomics.

Griffiths William J WJ Wang Yuqin Y

Biochemical and biophysical research communications 20180205 3

Oxysterols are oxidised derivatives of cholesterol or its precursors post lanosterol. They are intermediates in the biosynthesis of bile acids, steroid hormones and 1,25-dihydroxyvitamin D<sub>3.</sub> Although often considered as metabolic intermediates there is a growing body of evidence that many oxysterols are bioactive and their absence or excess may be part of the cause of a disease phenotype. Using global lipidomics approaches oxysterols are underrepresented encouraging the development of ...[more]

PMID: 29421651

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Project description:BackgroundCauses 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 findingsApoE*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%, p<0.001), CETP activity (-74%, p<0.001) and increased HDL-C (39%, p<0.05). It influenced lipidomics classes of cholesterol esters and triglycerides the most. Rimonabant induced a weight loss (-9%, p<0.05), but only a moderate improvement of lipid profiles. In vitro, SUB885C extract caused adipolysis stimulation and adipogenesis inhibition in 3T3-L1 cells.ConclusionsSUB885C, a multi-components preparation, is able to produce anti-atherogenic changes in lipids of the ApoE*3Leiden.CETP mice, which are comparable to those obtained with compounds belonging to known drugs (e.g. rimonabant, atorvastatin, niacin). This study successfully illustrated the power of lipidomics in unraveling intervention effects and to help finding new targets or ingredients for lifestyle-related metabolic abnormality.

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An update on oxysterol biochemistry: New discoveries in lipidomics.

Publications

An update on oxysterol biochemistry: New discoveries in lipidomics.

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