The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver
Open accessAbstract
Summary PPARα is activated by drugs to treat human disorders of lipid metabolism. Its endogenous ligand is unknown. PPARα-dependent gene expression is impaired with inactivation of fatty acid synthase (FAS), suggesting that FAS is involved in generation of a PPARα ligand. Here we demonstrate the FAS-dependent presence of a phospholipid bound to PPARα isolated from mouse liver. Binding was increased under conditions that induce FAS activity and displaced by systemic injection of a PPARα agonist. Mass spectrometry identified the species as 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Knockdown of CEPT1, required for phosphatidylcholine synthesis, suppressed PPARα-dependent gene expression. Interaction of 16:0/18:1-GPC with the PPARα ligand binding domain and co-activator peptide motifs was comparable to PPARα agonists, but interactions with PPARδ were weak and none were detected with PPARγ. Portal vein infusion of 16:0/18:1-GPC induced PPARα-dependent gene expression and decreased hepatic steatosis. These data suggest that 16:0/18:1-GPC is a physiologically relevant endogenous PPARα ligand.
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Kliewer, S. A., Sundseth, S. S., Jones, S. A., Brown, P. J., Wisely, G. B., Koble, C. S., Devchand, P., Wahli, W., Willson, T. M., Lenhard, J. M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4318 · Cited by 2,164
Forman, B. M., Chen, J., & Evans, R. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4312 · Cited by 2,116
Yki-Järvinen, H. (2004) · New England Journal of Medicine · doi:10.1056/nejmra041001 · Cited by 1,830
Cited by
Pawlak, M., Lefebvre, P., & Staels, B. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.10.039 · Cited by 1,578
Molecular Actions of PPARα in Lipid Metabolism and Inflammation
Bougarne, N., Weyers, B., Desmet, S. J., Deckers, J., Ray, D. W., Staels, B., & De Bosscher, K. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00064 · Cited by 898
Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease
Softic, S., Cohen, D. E., & Kahn, C. R. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4054-0 · Cited by 709
Peroxisomes: A Nexus for Lipid Metabolism and Cellular Signaling
Lodhi, I. J., & Semenkovich, C. F. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.002 · Cited by 605
Self-citationThe gut microbiota modulates host energy and lipid metabolism in mice
Velagapudi, V. R., Hezaveh, R., Reigstad, C. S., Gopalacharyulu, P., Yetukuri, L., Islam, S., Felin, J., Perkins, R., Borén, J., Orešič, M., et al. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m002774 · Cited by 589
Metadata
- Authors
- Chakravarthy, M. V., Lodhi, I. J., Yin, L., Malapaka, R. R. V., Xu, H. E., Turk, J., & Semenkovich, C. F.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 138
- Issue
- 3
- Pages
- 476-488
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2148403724
- Cited by
- 533
- References
- 3
- FWCI
- 12.84
- Type
- journal article
- Language
- en
- Open access
- bronze
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