title: Association of Plasma Ceramides and Sphingomyelin With VLDL apoB-100 Fractional Catabolic Rate Before and After Rosuvastatin Treatment.
abstract: BACKGROUND
  The objective of the study was to examine post hoc associations between plasma sphingolipids and lipoprotein kinetics in men with the metabolic syndrome after rosuvastatin treatment.
  
  
  METHODS
  Plasma sphingolipid profiling, determined by tandem mass spectrometry, was performed in a randomized, double-blind, triple-crossover trial (n = 12) of 5-week treatment periods with placebo or rosuvastatin (10 or 40 mg/d) with 2-week washouts between treatments.
  
  
  CONCLUSIONS
  Baseline plasma ceramides were associated with very low-density lipoprotein (VLDL) apolipoprotein (apo)-B-100 concentration (r = 0.58, P < .05) and inversely with VLDL apoB-100 fractional catabolic rate (FCR; r = -0.67, P = .02). Posttreatment changes with rosuvastatin (40 mg/d) in plasma ceramides were inversely associated with VLDL apoB-100 FCR (r = -0.62, P = .03) independent of changes in plasma triglycerides, cholesterol, and low-density lipoprotein-cholesterol. By contrast, baseline and postrosuvastatin treatment plasma sphingomyelin levels were not associated with apoB-100 kinetics. Plasma ceramides and sphingomyelin were not associated with the kinetics or concentrations of high-density lipoprotein apoA-I, and low-density lipoprotein apoB. In the metabolic syndrome, the ability of rosuvastatin to increase VLDL apoB-100 FCR may reflect ceramide-specific mechanistic actions and/or sphingolipid exchange.
authors: Metabolic Research Centre (T.W.K.N., E.M.M.O., G.F.W., D.C.C., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia and Lipid Disorders Clinic (G.F.W.), Department of Cardiovascular Medicine, Royal Perth Hospital, Faculty of Engineering, Computing, and Mathematics (P.H.R.B.), University of Western Australia, Perth, Western Australia 6847, Australia; and Metabolomics Laboratory (T.W.K.N., P.J.M.), Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors: Theodore W K
authors: TW
authors: Ng
authors: Metabolic Research Centre (T.W.K.N., E.M.M.O., G.F.W., D.C.C., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia and Lipid Disorders Clinic (G.F.W.), Department of Cardiovascular Medicine, Royal Perth Hospital, Faculty of Engineering, Computing, and Mathematics (P.H.R.B.), University of Western Australia, Perth, Western Australia 6847, Australia; and Metabolomics Laboratory (T.W.K.N., P.J.M.), Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors: Esther M M
authors: EM
authors: Ooi
authors: Metabolic Research Centre (T.W.K.N., E.M.M.O., G.F.W., D.C.C., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia and Lipid Disorders Clinic (G.F.W.), Department of Cardiovascular Medicine, Royal Perth Hospital, Faculty of Engineering, Computing, and Mathematics (P.H.R.B.), University of Western Australia, Perth, Western Australia 6847, Australia; and Metabolomics Laboratory (T.W.K.N., P.J.M.), Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors: Gerald F
authors: GF
authors: Watts
authors: Metabolic Research Centre (T.W.K.N., E.M.M.O., G.F.W., D.C.C., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia and Lipid Disorders Clinic (G.F.W.), Department of Cardiovascular Medicine, Royal Perth Hospital, Faculty of Engineering, Computing, and Mathematics (P.H.R.B.), University of Western Australia, Perth, Western Australia 6847, Australia; and Metabolomics Laboratory (T.W.K.N., P.J.M.), Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors: Dick C
authors: DC
authors: Chan
authors: Metabolic Research Centre (T.W.K.N., E.M.M.O., G.F.W., D.C.C., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia and Lipid Disorders Clinic (G.F.W.), Department of Cardiovascular Medicine, Royal Perth Hospital, Faculty of Engineering, Computing, and Mathematics (P.H.R.B.), University of Western Australia, Perth, Western Australia 6847, Australia; and Metabolomics Laboratory (T.W.K.N., P.J.M.), Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors: Peter J
authors: PJ
authors: Meikle
authors: Metabolic Research Centre (T.W.K.N., E.M.M.O., G.F.W., D.C.C., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia and Lipid Disorders Clinic (G.F.W.), Department of Cardiovascular Medicine, Royal Perth Hospital, Faculty of Engineering, Computing, and Mathematics (P.H.R.B.), University of Western Australia, Perth, Western Australia 6847, Australia; and Metabolomics Laboratory (T.W.K.N., P.J.M.), Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors: P Hugh R
authors: PH
authors: Barrett
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053299:Apolipoprotein B-100 / Q000097:blood* / Q000737:chemistry; D002518:Ceramides / Q000097:blood*; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008660:Metabolism / Q000187:drug effects; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000150:complications / Q000188:drug therapy; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013109:Sphingomyelins / Q000097:blood*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D002518:Ceramides; D005464:Fluorobenzenes; D008079:Lipoproteins, VLDL; D011743:Pyrimidines; D013109:Sphingomyelins; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium