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An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ)
Open accessAbstract
Thiazolidinedione derivatives are antidiabetic agents that increase the insulin sensitivity of target tissues in animal models of non-insulin-dependent diabetes mellitus. In vitro, thiazolidinediones promote adipocyte differentiation of preadipocyte and mesenchymal stem cell lines; however, the molecular basis for this adipogenic effect has remained unclear. Here, we report that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the nuclear receptor superfamily recently shown to function in adipogenesis. The most potent of these agents, BRL49653, binds to PPAR gamma with a Kd of approximately 40 nM. Treatment of pluripotent C3H10T1/2 stem cells with BRL49653 results in efficient differentiation to adipocytes. These data are the first demonstration of a high affinity PPAR ligand and provide strong evidence that PPAR gamma is a molecular target for the adipogenic effects of thiazolidinediones. Furthermore, these data raise the intriguing possibility that PPAR gamma is a target for the therapeutic actions of this class of compounds.
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“Rosiglitazone is the most effective drug among the two approved thiazolidinediones.482”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · doi:10.1038/s41392-025-02549-5 · cites this paper as [482]
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Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators
Issemann, I., & Green, S. (1990) · Nature · doi:10.1038/347645a0 · Cited by 3,519
Cited by
Lamb, J., Crawford, E. D., Peck, D., Modell, J. W., Blat, I. C., Wrobel, M. J., Lerner, J., Brunet, J.-P., Subramanian, A., Ross, K. N., et al. (2006) · Science · doi:10.1126/science.1132939 · Cited by 5,257
The hormone resistin links obesity to diabetes
Steppan, C. M., Bailey, S. T., Bhat, S., Brown, E. J., Banerjee, R. R., Wright, C. M., Patel, H. R., Ahima, R. S., & Lazar, M. A. (2001) · Nature · doi:10.1038/35053000 · Cited by 4,755
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143
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
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Metadata
- Authors
- Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M., & Kliewer, S. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-06
- Volume
- 270
- Issue
- 22
- Pages
- 12953-12956
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2047591801
- Cited by
- 3,625
- References
- 2
- FWCI
- 32.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ). https://app.cochat.ai/papers/10.1074/jbc.270.22.12953
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- Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M., & Kliewer, S. A. (1995). An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ). Journal of Biological Chemistry. https://doi.org/10.1074/jbc.270.22.12953
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
