PPARδ is a very low-density lipoprotein sensor in macrophages
Open accessAbstract
Although triglyceride-rich particles, such as very low-density lipoprotein (VLDL), contribute significantly to human atherogenesis, the molecular basis for lipoprotein-driven pathogenicity is poorly understood. We demonstrate that in macrophages, VLDL functions as a transcriptional regulator via the activation of the nuclear receptor peroxisome proliferator-activated receptor δ. The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein lipase. Generation of peroxisome proliferator-activated receptor δ null macrophages verifies the absolute requirement of this transcription factor in mediating the VLDL response. Thus, our data reveal a pathway through which dietary triglycerides and VLDL can directly regulate gene expression in atherosclerotic lesions.
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Prior studies report that PPARδ contributes to PLIN2 and CD36 expression.
“These findings are in line with studies reporting the contribution of PPARd to PLIN2 (Chawla et al., 2003;Fan et al., 2009) and CD36 (Li et al., 2004;Bojic et al., 2012) expression.”
PPARd selectively responds to different stimuli of lipid metabolism; VLDL reliably activates PPARd, whereas HDL and LDL do not.
“Furthermore, PPARd selectively responds to different”
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Cites
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- Authors
- Chawla, A., Lee, C.-H., Barak, Y., He, W., Rosenfeld, J., Liao, D., Han, J., Kang, H., & Evans, R. M.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Evans, Ronald M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-01-22
- Volume
- 100
- Issue
- 3
- Pages
- 1268-1273
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC298762
- OpenAlex
- W1970669390
- Cited by
- 305
- References
- 7
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 8 · 2015: 11 · 2014: 6 · 2013: 12 · 2012: 12
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- March of Dimes Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- PPARδ, VLDL, macrophages, atherosclerosis, triglycerides, lipoprotein lipase, nuclear receptor signaling, transcriptional regulation, dietary triglycerides, atherogenesis
- MeSH terms
- Alleles, Animals, Dose-Response Relationship, Drug, Flow Cytometry, Genetic Vectors, Lipoproteins, VLDL, Macrophages, Models, Genetic, Oxygen, Promoter Regions, Genetic, Time Factors, Transcription Factors, Transcription, Genetic, Transfection, Blotting, Northern, Signal Transduction, 3T3 Cells, Point Mutation, Genes, Reporter, Receptors, Cytoplasmic and Nuclear, Lipid Metabolism, Mice
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