Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia.
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.
Baker IDI Heart and Diabetes Institute, Melbourne, Australia peter.meikle@bakeridi.edu.au.
Peter J
PJ
Meikle
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Gerard
G
Wong
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Ricardo
R
Tan
Dyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, and University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, Paris, France.
Philippe
P
Giral
Dyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, and University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, Paris, France.
Paul
P
Robillard
Dyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, and University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, Paris, France.
Alexina
A
Orsoni
Kowa Research Europe Ltd., Wokingham, United Kingdom.
Neil
N
Hounslow
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Dianna J
DJ
Magliano
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Jonathan E
JE
Shaw
South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio, Harlingen, TX.
Joanne E
JE
Curran
South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio, Harlingen, TX.
John
J
Blangero
Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Bronwyn A
BA
Kingwell
Dyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, and University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, Paris, France.
M John
MJ
Chapman
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy*; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D050171:Dyslipidemias / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D044882:Glucose Metabolism Disorders / Q000097:blood* / Q000139:chemically induced; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008074:Lipoproteins; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000188:drug therapy*; D008875:Middle Aged; D014280:Triglycerides
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol
cholesterol; lipidomics; metabolic syndrome; obesity; omega-3 fatty acids; pitavastatin; plasmalogens