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    Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia

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    Author
    Meikle, PJ; Wong, G; Tan, R; Giral, P; Robillard, P; Orsoni, A; Hounslow, N; Magliano, DJ; Shaw, JE; Curran, JE; ...
    Date
    2015-12-01
    Source Title
    Journal of Lipid Research
    Publisher
    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
    University of Melbourne Author/s
    Meikle, Peter; Kingwell, Bronwyn; Magliano, Dianna
    Affiliation
    Bio21
    Physiology
    Melbourne School of Population and Global Health
    Metadata
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    Document Type
    Journal Article
    Citations
    Meikle, P. J., Wong, G., Tan, R., Giral, P., Robillard, P., Orsoni, A., Hounslow, N., Magliano, D. J., Shaw, J. E., Curran, J. E., Blangero, J., Kingwell, B. A. & Chapman, M. J. (2015). Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia. JOURNAL OF LIPID RESEARCH, 56 (12), pp.2381-2392. https://doi.org/10.1194/jlr.P061143.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256697
    DOI
    10.1194/jlr.P061143
    Abstract
    The impact of statin treatment on the abnormal plasma lipidome of mixed dyslipidemic patients with metabolic syndrome (MetS), a group at increased risk of developing diabetes, was evaluated. Insulin-resistant hypertriglyceridemic hypertensive obese males (n = 12) displaying MetS were treated with pitavastatin (4 mg/day) for 180 days; healthy normolipidemic age-matched nonobese males (n = 12) acted as controls. Statin treatment substantially normalized triglyceride (-41%), remnant cholesterol (-55%), and LDL-cholesterol (-39%), with minor effect on HDL-cholesterol (+4%). Lipidomic analysis, normalized to nonHDL-cholesterol in order to probe statin-induced differences in molecular composition independently of reduction in plasma cholesterol, revealed increment in 132 of 138 lipid species that were subnormal at baseline and significantly shifted toward the control group on statin treatment. Increment in alkyl- and alkenylphospholipids (plasmalogens) was prominent, and consistent with significant statin-induced increase in plasma polyunsaturated fatty acid levels. Comparison of the statin-mediated lipidomic changes in MetS with the abnormal plasma lipidomic profile characteristic of prediabetes and T2D in the Australian Diabetes, Obesity, and Lifestyle Study and San Antonio Family Heart Study cohorts by hypergeometric analysis revealed a significant shift toward the lipid profile of controls, indicative of a marked trend toward a normolipidemic phenotype. Pitavastatin attenuated the abnormal plasma lipidome of MetS patients typical of prediabetes and T2D.

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