The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
The Peroxisome Proliferator-activated Receptor δ Promotes Lipid Accumulation in Human Macrophages
Open accessAbstract
The peroxisome proliferator-activated receptors (PPARs) are a family of fatty acid-activated transcription factors which control lipid homeostasis and cellular differentiation. PPARalpha (NR1C1) controls lipid oxidation and clearance in hepatocytes and PPARgamma (NR1C3) promotes preadipocyte differentiation and lipogenesis. Drugs that activate PPARalpha are effective in lowering plasma levels of lipids and have been used in the management of hyperlipidemia. PPARgamma agonists increase insulin sensitivity and are used in the management of type 2 diabetes. In contrast, there are no marketed drugs that selectively target PPARdelta (NR1C2) and the physiological roles of PPARdelta are unclear. In this report we demonstrate that the expression of PPARdelta is increased during the differentiation of human macrophages in vitro. In addition, a highly selective agonist of PPARdelta (compound F) promotes lipid accumulation in primary human macrophages and in macrophages derived from the human monocytic cell line, THP-1. Compound F increases the expression of genes involved in lipid uptake and storage such as the class A and B scavenger receptors (SRA, CD36) and adipophilin. PPARdelta activation also represses key genes involved in lipid metabolism and efflux, i.e. cholesterol 27-hydroxylase and apolipoprotein E. We have generated THP-1 sublines that overexpress PPARdelta and have confirmed that PPARdelta is a powerful promoter of macrophage lipid accumulation. These data suggest that PPARdelta may play a role in the pathology of diseases associated with lipid-filled macrophages, such as atherosclerosis, arthritis, and neurodegeneration.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“This is likely reasoned by the abundant expression of PPARd, a hallmark of THP-1 cell differentiation (Vosper et al., 2001) (Supplemental Fig. 16).”
The cited source says what the claim attributes to it.
In the citing paper
“Consequently, the PPARd activation promotes lipid accumulation in THP-1 macrophages in the presence of serum (Vosper et al., 2001).”
The cited source says what the claim attributes to it.
In the citing paper
“As we did not use any lipoproteins as stimulus, the studies of Vosper et al. (2001) on PPARd and lipid accumulation in macrophages most accurately resemble our experimental setup.”
The cited source says what the claim attributes to it.
In the citing paper
“In line with our findings, the treatment with a PPARd agonist upregulated the expression of genes involved in lipid metabolism, including CD36 and PLIN2, in this study.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor
Tontonoz, P., Hu, E., & Spiegelman, B. M. (1994) · Cell · doi:10.1016/0092-8674(94)90006-x · Cited by 3,564
The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J., & Glass, C. K. (1998) · Nature · doi:10.1038/34178 · Cited by 3,525
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
Jiang, C., Ting, A. T., & Seed, B. (1998) · Nature · doi:10.1038/34184 · Cited by 2,899
15-Deoxy-Δ12,14-Prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ
FORMAN, B. M., Tontonoz, P., Chen, J., Brun, R. P., Spiegelman, B. M., & Evans, R. M. (1995) · Cell · doi:10.1016/0092-8674(95)90193-0 · Cited by 2,857
Apolipoprotein E polymorphism and atherosclerosis.
Davignon, J., Gregg, R. E., & Sing, C. F. (1988) · Arteriosclerosis: An Official Journal of the American Heart Association, Inc. · doi:10.1161/01.atv.8.1.1 · Cited by 1,981
Roles of PPARs in health and disease
Kersten, S., Desvergne, B., & Wahli, W. (2000) · Nature · doi:10.1038/35013000 · Cited by 1,956
Oxidized LDL Regulates Macrophage Gene Expression through Ligand Activation of PPARγ
Nagy, L., Tontonoz, P., Alvarez, J. G. A., Chen, H.-W., & Evans, R. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81574-3 · Cited by 1,861
PPARγ Promotes Monocyte/Macrophage Differentiation and Uptake of Oxidized LDL
Tontonoz, P., Nagy, L., Alvarez, J. G. A., Thomázy, V. A., & Evans, R. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81575-5 · Cited by 1,815
Kliewer, S. A., Umesono, K., Noonan, D. J., Heyman, R. A., & Evans, R. M. (1992) · Nature · doi:10.1038/358771a0 · Cited by 1,746
Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase
Rossi, A., Kapahi, P., Natoli, G., Takahashi, T., Chen, Y., Karin, M., & Santoro, M. G. (2000) · Nature · doi:10.1038/47520 · Cited by 1,303
Flagged first, then by citations
Research works printed but not linked: 3
- Cullen, 1987, Methods Enzymol., 152, 692
- Wu, 1994, Mol. Cell. Biol., 14, 2129
- Kang, 1997, Mutat. Res., 382, 57
Cited by
Sorted by citations
Lipids and Lipid-Based Formulations: Optimizing the Oral Delivery of Lipophilic Drugs
Porter, C. J. H., Trevaskis, N. L., & Charman, W. N. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2197 · Cited by 1,824
Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity
Wang, Y.-X., Lee, C.-H., Tiep, S., Yu, R. T., Ham, J., Kang, H., & Evans, R. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00269-1 · Cited by 1,296
Emerging roles of PPARS in inflammation and immunity
Daynes, R. A., & Jones, D. C. (2002) · Nature reviews. Immunology · doi:10.1038/nri912 · Cited by 926
Minireview: Lipid Metabolism, Metabolic Diseases, and Peroxisome Proliferator-Activated Receptors
Lee, C., Olson, P., & Evans, R. M. (2003) · Endocrinology · doi:10.1210/en.2003-0288 · Cited by 891
The role of peroxisome proliferator-activated receptors (PPAR) in immune responses
Christofides, A., Konstantinidou, E., Jani, C., & Boussiotis, V. A. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154338 · Cited by 746
Metadata
- Authors
- Vosper, H., Patel, L., Graham, T. L., Khoudoli, G. A., Hill, A., Macphee, C. H., Pinto, I., Smith, S. A., Suckling, K. E., Wolf, C. R., & Palmer, C. N. A.
- Affiliations
- Ninewells Hospital (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Palmer, Colin N.A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 276
- Issue
- 47
- Pages
- 44258-44265
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2103618523
- Cited by
- 268
- References
- 49
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 2 · 2013: 10 · 2012: 7
- FWCI
- 8.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Funders
- British Heart Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- PPARδ, peroxisome proliferator-activated receptors, macrophage lipid accumulation, macrophage differentiation, compound F, scavenger receptors, CD36, adipophilin, apolipoprotein E, lipid metabolism, atherosclerosis, THP-1 cells
- MeSH terms
- Animals, Cell Line, Cholesterol, Gene Expression Regulation, Humans, Macrophages, Transcription Factors, Receptors, Cytoplasmic and Nuclear, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
