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

Abstract

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.

Comprehensive Plasma Metabolomic Analyses of Atherosclerotic Progression Reveal Alterations in Glycerophospholipid and Sphingolipid Metabolism in Apolipoprotein E-deficient Mice

“…These lipids are not only structural components of biological membranes, but also act as signaling molecules and bioactive mediators in important atherosclerosis-related cellular processes, including apoptosis, angiogenesis, inflammation and proliferation 18 19 20 21 22 . Disturbances in their metabolism have been previously observed in atherosclerosis-related diseases 23 24 25 ; however, to the best of our knowledge, we are the first group to identify the specific pathways within these metabolic systems that are associated with the specific stages of atherosclerotic progression.…”

Looking back into the future: 30 years of metabolomics at TNO

“…Effects of various ages of Ginseng root extracts were compared in a diabetic rat model (Hu et al, ). The APOE3 Leiden mouse model was used to test effects of Rimonabant and a Chinese herbal formula on lipid profiles (Hu et al, ; Wei et al, ). The Chinese formula was shown to reduce plasma cholesterol, cholesteryl ester transfer protein (CETP) levels, and CETP activity, and to increase high‐density lipoprotein (HDL) cholesterol.…”

“…Effects of various ages of Ginseng root extracts were compared in a diabetic rat model (Hu et al, 2011). The APOE3 Leiden mouse model was used to test effects of Rimonabant and a Chinese herbal formula on lipid profiles (Hu et al, 2011c;Wei et al, 2012a).…”

Clinical Implications

“…Diacylglycerols, in general, and the DG 16 diseases. [18][19][20][21][22] The advantages of this method are high resolution, accuracy, and associative information at the level of lipid species. 23,24 It is noteworthy that serum lipidomic studies have already offered critical insights in the pathogenesis of complex diseases, such as obesity and insulin resistance.…”