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J Lipid Res. 2015 Dec;56(12):2381-92. doi: 10.1194/jlr.P061143. Epub 2015 Oct 20.

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

Author information

1
Baker IDI Heart and Diabetes Institute, Melbourne, Australia peter.meikle@bakeridi.edu.au.
2
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
3
Dyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, and University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, Paris, France.
4
Kowa Research Europe Ltd., Wokingham, United Kingdom.
5
South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio, Harlingen, TX.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01595828.

KEYWORDS:

cholesterol; lipidomics; metabolic syndrome; obesity; omega-3 fatty acids; pitavastatin; plasmalogens

PMID:
26486974
PMCID:
PMC4655992
DOI:
10.1194/jlr.P061143
[Indexed for MEDLINE]
Free PMC Article

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