The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Conditional Disruption of the Peroxisome Proliferator-Activated Receptor γ Gene in Mice Results in Lowered Expression of ABCA1, ABCG1, and apoE in Macrophages and Reduced Cholesterol Efflux
Open accessAbstract
Disruption of the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene causes embryonic lethality due to placental dysfunction. To circumvent this, a PPAR gamma conditional gene knockout mouse was produced by using the Cre-loxP system. The targeted allele, containing loxP sites flanking exon 2 of the PPAR gamma gene, was crossed into a transgenic mouse line expressing Cre recombinase under the control of the alpha/beta interferon-inducible (MX) promoter. Induction of the MX promoter by pIpC resulted in nearly complete deletion of the targeted exon, a corresponding loss of full-length PPAR gamma mRNA transcript and protein, and marked reductions in basal and troglitazone-stimulated expression of the genes encoding lipoprotein lipase, CD36, LXR alpha, and ABCG1 in thioglycolate-elicited peritoneal macrophages. Reductions in the basal levels of apolipoprotein E (apoE) mRNA in macrophages and apoE protein in total plasma and high-density lipoprotein (HDL) were also observed in pIpC-treated PPAR gamma-MXCre(+) mice. Basal cholesterol efflux from cholesterol-loaded macrophages to HDL was significantly reduced after disruption of the PPAR gamma gene. Troglitazone selectively inhibited ABCA1 expression (while rosiglitazone, ciglitazone, and pioglitazone had little effect) and cholesterol efflux in both PPAR gamma-deficient and control macrophages, indicating that this drug can exert paradoxical effects on cholesterol homeostasis that are independent of PPAR gamma. Together, these data indicate that PPAR gamma plays a critical role in the regulation of cholesterol homeostasis by controlling the expression of a network of genes that mediate cholesterol efflux from cells and its transport in plasma.
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“Nearly complete disruption of the PPAR gene was also demonstrated in the liver (not shown), a finding consistent with the results of earlier studies with the MX-Cre transgene in which a nearly complete pIpC deletion was shown in the liver (a tissue in which PPAR is not well expressed) and macrophages (44, 68, 72).”
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Cited by
Macrophage-specific PPARγ controls alternative activation and improves insulin resistance
Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., Eagle, A. R., Vats, D., Brombacher, F., Ferrante, A. W., et al. (2007) · Nature · doi:10.1038/nature05894 · Cited by 2,107
Fat and Beyond: The Diverse Biology of PPARγ
Tontonoz, P., & Spiegelman, B. M. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061307.091829 · Cited by 2,085
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
PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells
Cipolletta, D., Feuerer, M., Li, A., Kamei, N., Lee, J., Shoelson, S. E., Benoist, C., & Mathis, D. (2012) · Nature · doi:10.1038/nature11132 · Cited by 1,143
Feige, J. N., Gelman, L., Michalik, L., Desvergne, B., & Wahli, W. (2006) · Progress in Lipid Research · doi:10.1016/j.plipres.2005.12.002 · Cited by 786
Metadata
- Authors
- Akiyama, T. E., Sakai, S., Lambert, G., Nicol, C. J., Matsusue, K., Pimprale, S., Lee, Y.-H., Ricote, M., Glass, C. K., Brewer, H. B., & Gonzalez, F. J.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2002-04-01
- Volume
- 22
- Issue
- 8
- Pages
- 2607-2619
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2115837052
- Cited by
- 368
- References
- 10
- FWCI
- 29.95
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Conditional Disruption of the Peroxisome Proliferator-Activated Receptor γ Gene in Mice Results in Lowered Expression of ABCA1, ABCG1, and apoE in Macrophages and Reduced Cholesterol Efflux. https://app.cochat.ai/papers/10.1128/mcb.22.8.2607-2619.2002
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- Akiyama, T. E., Sakai, S., Lambert, G., Nicol, C. J., Matsusue, K., Pimprale, S., Lee, Y.-H., Ricote, M., Glass, C. K., Brewer, H. B., & Gonzalez, F. J. (2002). Conditional Disruption of the Peroxisome Proliferator-Activated Receptor γ Gene in Mice Results in Lowered Expression of ABCA1, ABCG1, and apoE in Macrophages and Reduced Cholesterol Efflux. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.22.8.2607-2619.2002
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
