Trial reportArteriosclerosis, thrombosis, and vascular biology2009
Potent and selective PPAR-alpha agonist LY518674 upregulates both ApoA-I production and catabolism in human subjects with the metabolic syndrome.
Trial report in Arteriosclerosis, thrombosis, and vascular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 42 citations in OpenAlex.
- ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2021Trial
- Potent peroxisome proliferator-activated receptor-α agonist treatment increases cholesterol efflux capacity in humans with the metabolic syndrome.European heart journal · 2015Trial
- Calculated Excess-Triglyceride Based on the Friedewald Formula is a Possible Surrogate Marker for the Production of Large Very-Low Density Lipoprotein, A Post-Hoc Analysis of the PROUD48 Study.Journal of atherosclerosis and thrombosis · 2026Article
- Functional interaction between immune checkpoints and lipid metabolism in the development of arteriosclerosis obliterans.Frontiers in immunology · 2025Review
- Effectiveness of One-Year Pemafibrate Therapy on Non-Alcoholic Fatty Liver Disease Refractory to Long-Term Sodium Glucose Cotransporter-2 Inhibitor Therapy: A Pilot Study.Life (Basel, Switzerland) · 2023Article
- Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease.Molecules (Basel, Switzerland) · 2021Article
- Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARMα) in the Metabolic Syndrome: Is Pemafibrate Light at the End of the Tunnel?Current atherosclerosis reports · 2021Review
- ApoA-I-Directed Therapies for the Management of Atherosclerosis.Current atherosclerosis reports · 2015Review
- Quantitation of [5-14CH3]-(2R, 4'R, 8'R)-α-tocopherol in humans.The Journal of nutrition · 2011Article
- Peroxisome proliferator-activated receptor-α activation promotes macrophage reverse cholesterol transport through a liver X receptor-dependent pathway.Arteriosclerosis, thrombosis, and vascular biology · 2011Article
- Review
- Future therapeutic directions in reverse cholesterol transport.Current atherosclerosis reports · 2010Review
- Update on strategies to increase HDL quantity and function.Nature reviews. Cardiology · 2009Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe study of PPAR-alpha activation on apoA-I production in humans has been limited to fibrates, relatively weak PPAR-alpha agonists that may have other molecular effects. We sought to determine the effect of a potent and highly specific PPAR-alpha agonist, LY518674, on apoA-I, apoA-II, and apoB-100 kinetics in humans with metabolic syndrome and low levels of HDL cholesterol (C). METHODS AND
resultsSubjects were randomized to receive LY518674 (100 microg) once daily (n=13) or placebo (n=15) for 8 weeks. Subjects underwent a kinetic study using a deuterated leucine tracer to measure apolipoprotein production and fractional catabolic rates (FCR) at baseline and after treatment. LY518674 significantly reduced VLDL-C (-38%, P=0.002) and triglyceride (-23%, P=0.002) levels whereas LDL-C and HDL-C levels were unchanged. LY518674 significantly reduced VLDL apoB-100 (-12%, P=0.01) levels, attributable to an increased VLDL apoB-100 FCR with no change in VLDL apoB-100 production. IDL and LDL apoB-100 kinetics were unchanged. LY518674 significantly increased the apoA-I production rate by 31% (P<0.0001), but this was accompanied by a 33% increase in the apoA-I FCR (P=0.002), resulting in no change in plasma apoA-I. There was a 71% increase in the apoA-II production rate (P<0.0001) accompanied by a 25% increase in the FCR (P<0.0001), resulting in a significant increase in plasma apoA-II.
conclusionsActivation of PPAR-alpha with LY518674 (100 microg) in subjects with metabolic syndrome and low HDL-C increased the VLDL apoB-100 FCR consistent with enhanced lipolysis of plasma triglyceride. Significant increases in the apoA-I and apoA-II production rates were accompanied by increased FCRs resulting in no change in HDL-C levels. These data indicate a major effect of LY518674 on the production and clearance of apoA-I and HDL despite no change in the plasma concentration. The effect of these changes on reverse cholesterol transport remains to be determined.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.