title: Lipidomics reveals multiple pathway effects of a multi-components preparation on lipid biochemistry in ApoE*3Leiden.CETP mice.
abstract: 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.
  
  
  RESULTS
  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%, 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.
  
  
  CONCLUSIONS
  SUB885C, 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.
authors.affiliation: Department of Earth, Environmental and Life Science, TNO, Zeist, The Netherlands.
authors.forename: Heng
authors.initials: H
authors.lastname: Wei
authors.forename: Chunxiu
authors.initials: C
authors.lastname: Hu
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Anita M
authors.initials: AM
authors.lastname: van den Hoek
authors.forename: Theo H
authors.initials: TH
authors.lastname: Reijmers
authors.forename: Suzan
authors.initials: S
authors.lastname: Wopereis
authors.forename: Jildau
authors.initials: J
authors.lastname: Bouwman
authors.forename: Raymond
authors.initials: R
authors.lastname: Ramaker
authors.forename: Henrie A A J
authors.initials: HA
authors.lastname: Korthout
authors.forename: Marco
authors.initials: M
authors.lastname: Vennik
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Renger F
authors.initials: RF
authors.lastname: Witkamp
authors.forename: Elwin R
authors.initials: ER
authors.lastname: Verheij
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D053318:Apolipoprotein E3 / Q000235:genetics* / Q000378:metabolism; D001671:Biochemistry; D001835:Body Weight / Q000187:drug effects; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D008055:Lipids / Q000032:analysis* / Q000737:chemistry; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D000077285:Rimonabant
chemical_list: D000924:Anticholesteremic Agents; D053318:Apolipoprotein E3; D053480:Cholesterol Ester Transfer Proteins; D004365:Drugs, Chinese Herbal; D008055:Lipids; D010880:Piperidines; D011720:Pyrazoles; C572441:SUB885C; D000077285:Rimonabant