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

Peter J. Meikle, Gerard Wong, Ricardo Tan, Philippe Giral, Paul Robillard, Alexina Orsoni, Neil Hounslow, Dianna J. Magliano, Jonathan E. Shaw, Joanne E. Curran, John Blangero, Bronwyn A. Kingwell, M. John Chapman

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20 Citations (Scopus)

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 ( ô 41%), remnant cholesterol ( ô 55%), and LDLcholesterol ( ô 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 alkyland 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.

Original languageEnglish
Pages (from-to)2381-2392
Number of pages12
JournalJournal of Lipid Research
Volume56
Issue number12
DOIs
Publication statusPublished - Dec 2015
Externally publishedYes

Keywords

  • Cholesterol
  • Lipidomics
  • Metabolic syndrome
  • Obesity
  • Omega-3 fatty acids
  • Pitavastatin
  • Plasmalogens

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