Publication Date:
2012-08-16
Description:
Objective— Peroxisome proliferator-activated receptor-–induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins. Methods and Results— GW501516 (2.5, 5.0, or 10.0 mg) or placebo was given for 12 weeks to patients (n=268) with high-density lipoprotein (HDL) cholesterol 〈1.16 mmol/L. Fasting lipids/apolipoproteins (apos), insulin, glucose, and free fatty acid were measured; changes from baseline were calculated and assessed. A second smaller exploratory study (n=37) in a similar population was conducted using a sequence of 5 and 10 mg dosing for the assessment of lipoprotein particle concentration. GW501516 demonstrated HDL cholesterol increases up to 16.9% (10 mg) and apoA-I increases up to 6.6%. Reductions were observed in low-density lipoprotein (LDL) cholesterol (–7.3%), triglycerides (–16.9%), apoB (–14.9%), and free fatty acids (–19.4%). The exploratory study showed significant reductions in the concentration of very LDL (–19%), intermediate-density lipoprotein (–52%), and LDL (–14%, predominantly a reduction in small particles), whereas the number of HDL particles increased (+10%; predominantly medium and large HDL). Conclusion— GW501516 produced significant changes in HDL cholesterol, LDL cholesterol, apoA1, and apoB. Fewer very LDL and larger LDL support a transition toward less atherogenic lipoprotein profiles. These data are consistent with peroxisome proliferator-activated receptor- being a potentially important target for providing cardiovascular protection in metabolic syndrome-like patients.
Keywords:
Lipid and lipoprotein metabolism
Print ISSN:
1079-5642
Electronic ISSN:
1524-4636
Topics:
Medicine
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