Cyclic phosphatidic acid (1-acyl-2,3-cyclic-glycerophosphate, CPA), one of nature's simplest phospholipids, is found in cells from slime mold to humans and has a largely unknown function. We find here that CPA is generated in mammalian cells in a stimulus-coupled manner by phospholipase D2 (PLD2) and binds to and inhibits the nuclear hormone receptor PPARgamma with nanomolar affinity and high specificity through stabilizing its interaction with the corepressor SMRT. CPA production inhibits the PPARgamma target-gene transcription that normally drives adipocytic differentiation of 3T3-L1 cells, lipid accumulation in RAW264.7 cells and primary mouse macrophages, and arterial wall remodeling in a rat model in vivo. Inhibition of PLD2 by shRNA, a dominant-negative mutant, or a small molecule inhibitor blocks CPA production and relieves PPARgamma inhibition. We conclude that CPA is a second messenger and a physiological inhibitor of PPARgamma, revealing that PPARgamma is regulated by endogenous agonists as well as by antagonists.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446787 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2010.07.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Autoimmune Thyroid Disease and Pregnancy: The Interaction Between Genetics, Epigenetics and Environmental Factors.
J Clin Med
December 2024
Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia.
Autoimmune thyroid disease (AITD) is the leading cause of thyroid dysfunction globally, characterized primarily by two distinct clinical manifestations: Hashimoto's thyroiditis (HT) and Graves' disease (GD). The prevalence of AITD is approximately twice as high in women compared to men, with a particularly pronounced risk during the reproductive years. Pregnancy exerts profound effects on thyroid physiology and immune regulation due to hormonal fluctuations and immune adaptations aimed at fostering maternal-fetal tolerance, potentially triggering or exacerbating AITD.
View Article and Find Full Text PDFGenome-Wide Characterization of the Heat Shock Transcription Factor Gene Family in Reveals Promising Candidates for Heat Tolerance.
Int J Mol Sci
December 2024
College of Jixian Honors, Zhejiang Agriculture and Forestry University, Hangzhou 311300, China.
Heat stress transcription factors (HSFs) play a critical role in orchestrating cellular responses to elevated temperatures and various stress conditions. While extensively studied in model plants, the gene family in remains unexplored, despite the availability of its sequenced genome. In this study, we employed bioinformatics approaches to identify 21 genes within the genome, revealing their uneven distribution across chromosomes.
View Article and Find Full Text PDFPTHrP Promotes RBP4 Expression Under the Control of PPARγ in the Kidney.
Int J Mol Sci
December 2024
Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, 28922 Alcorcón, Madrid, Spain.
Article Synopsis
- PTHrP and RBP4 are linked to worse kidney disease outcomes, and their relationship with PPARγ, a protective nuclear receptor, was investigated.
- The study examined levels of these proteins in different mouse models, including controls, diabetics, and those overexpressing PTHrP.
- Findings indicated that RBP4 and PTHrP levels increase during kidney pathology, suggesting that insulin and PPARγ play crucial roles in regulating their expression to maintain kidney health.
The Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge.
Int J Mol Sci
December 2024
Nuclear Medicine Department, University of Medicine and Pharmacy "Carol Davila" Bucharest, 050474 Bucharest, Romania.
Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of ¹³¹I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2/IL-33R, and cTn I) in 74 female patients with DTC/-T2DM and 25 with DTC/+T2DM treated with metformin. All patients received a cumulative oral dose of I exceeding 150 mCi (5.
View Article and Find Full Text PDFMastectomy, HER2 Receptor Positivity, NPI, Late Stage and Luminal B-Type Tumor as Poor Prognostic Factors in Geriatric Patients with Breast Cancer.
Diagnostics (Basel)
December 2024
Department of Biostatistics and Medical Informatics, Division of Basic Medical Sciences, Faculty of Medicine, Recep Tayyip Erdoğan University, 53020 Rize, Turkey.
This study aims to explore the risk factors associated with poor survival outcomes in geriatric female patients with breast cancer. This study utilized data from the METABRIC database to evaluate the risk factors associated with poor survival outcomes among geriatric breast cancer patients. A total of 2909 female patients, 766 of whom were geriatric, were included in the study.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!