ArticleProceedings of the National Academy of Sciences of the United States of America2003
Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: evidence for an antiinflammatory role for lipoprotein lipase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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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.
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Who cites it
81 citing papers in PubMed, 250 citations in OpenAlex.
- Effect of omega-3 fatty acid ethyl esters on the oxylipin composition of lipoproteins in hypertriglyceridemic, statin-treated subjects.PloS one · 2014Trial
- The peroxisome proliferator-activated receptor-gamma agonist pioglitazone represses inflammation in a peroxisome proliferator-activated receptor-alpha-dependent manner in vitro and in vivo in mice.Journal of the American College of Cardiology · 2008Trial
- Identification of lipid metabolism-related genes in myocardial infarction: implications for diagnosis and therapy.Journal of cardiothoracic surgery · 2025Article
- Selective PPARα Modulator (SPPARMα) in the Era of the MASLD Pandemic: Current Insights and Future Prospects.Yonago acta medica · 2025Review
- Impact of Selective Peroxisome Proliferator-Activated Receptor (PPAR)-α Modulators and Fibrates on Microvascular Disease: Is There Still Room?Current atherosclerosis reports · 2025Review
- Anti-Inflammatory Effect of Dietary Pentadecanoic Fatty Acid Supplementation on Inflammatory Bowel Disease in SAMP1/YitFc Mice.Nutrients · 2024Article
- Cladosporols and PPARγ: Same Gun, Same Bullet, More Targets.Biomolecules · 2024Review
- Fat-tail allele-specific expression genes may affect fat deposition in tail of sheep.PloS one · 2024Article
- Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis.Nature communications · 2023Article
- Serum Levels of Lipoprotein Lipase Are Increased in Patients with Inflammatory Bowel Disease.International journal of molecular sciences · 2023Article
- Anti-Inflammatory, Antioxidant, and WAT/BAT-Conversion Stimulation Induced by Novel PPAR Ligands: Results from Ex Vivo and In Vitro Studies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The Role of PPARs in Breast Cancer.Cells · 2022Review
- Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice.PloS one · 2022Article
- Whole-body insulin resistance and energy expenditure indices, serum lipids, and skeletal muscle metabolome in a state of lipoprotein lipase overexpression.Metabolomics : Official journal of the Metabolomic Society · 2021Article
- The Glitazars Paradox: Cardiotoxicity of the Metabolically Beneficial Dual PPARα and PPARγ Activation.Journal of cardiovascular pharmacology · 2020Review
- Dual peroxisome-proliferator-activated-receptor-α/γ activation inhibits SIRT1-PGC1α axis and causes cardiac dysfunction.JCI insight · 2019Article
- The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.Cardiovascular diabetology · 2019Review
- Transcriptomics analysis reveals candidate genes and pathways for susceptibility or resistance to Singapore grouper iridovirus in orange-spotted grouper (Epinephelus coioides).Developmental and comparative immunology · 2019Article
- Article
- Maresin 1 attenuates pro-inflammatory reactions and ER stress in HUVECs via PPARα-mediated pathway.Molecular and cellular biochemistry · 2018Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Increased levels of triglyceride-rich lipoproteins provoke lipid accumulation in the artery wall, triggering early inflammatory responses central to atherosclerosis like endothelial adhesion molecule expression. The endogenous mechanisms limiting such reactions remain poorly defined. Lipoprotein lipase (LPL) plays a central role in lipid metabolism by hydrolyzing triglyceride rich lipoproteins and releasing fatty acids. We found that LPL treatment reversed tumor necrosis factor alpha and very low-density lipoprotein (VLDL)-stimulated endothelial vascular cell adhesion molecule 1 (VCAM1) induction and VCAM1 promoter responses, thus recapitulating effects reported with synthetic peroxisome proliferator-activated receptor (PPAR) agonists. In fact, these LPL effects on VCAM1 were absent in endothelial cells isolated from PPAR alpha-deficient mice. This finding suggests a novel antiinflammatory role for LPL. Further studies reveal specificity for PPAR activation through lipolysis in regards to lipoprotein substrate (VLDL >> LDL > HDL), PPAR isoform (PPAR alpha >> PPAR delta > PPAR gamma), and among fatty acid-releasing lipases. These PPAR responses required intact LPL catalytic activity. In vivo, transgenic mice overexpressing LPL had increased peroxisome proliferation, but not in the genetic absence of PPAR alpha. Although human plasma possesses minimal PPAR alpha activation despite containing abundant free fatty acids, marked PPAR alpha activation is seen with human plasma after LPL is added in vitro or systemically released in vivo. These data suggest a previously uncharacterized pathway in which the key lipolytic enzyme LPL can act on circulating lipoproteins to generate PPAR alpha ligands, providing a potentially important link between lipoprotein metabolism and distal PPAR alpha transcriptional effects.
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Registered trials
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.