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Event: 233
Key Event Title
Decreased, PPAR-gamma activation
Short name
Biological Context
Level of Biological Organization |
---|
Molecular |
Cell term
Cell term |
---|
hepatocyte |
Organ term
Key Event Components
Process | Object | Action |
---|---|---|
peroxisome proliferator activated receptor signaling pathway | peroxisome proliferator-activated receptor gamma | decreased |
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis | MolecularInitiatingEvent | Michelle Angrish (send email) | Under Development: Contributions and Comments Welcome | |
ROS formation leads to cancer via PPAR pathway | KeyEvent | John Frisch (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Life Stages
Life stage | Evidence |
---|---|
All life stages | Not Specified |
Sex Applicability
Term | Evidence |
---|---|
Unspecific | Not Specified |
Key Event Description
The Peroxisome Proliferator-Activated Receptors (PPAR) family of genes involved in regulation of lipid metabolism and energy pathways (Desvergne and Wahli 1999, Hihi et al. 2002, Ahmed et al. 2007). Fatty acids stimulate the expression of PPAR genes, which initiate a variety of cellular responses focused on lipid metabolism, but also inflammation and apoptosis pathways. Decreases in PPAR-gamma expression are associated with disruption of adipocyte differentiation and glucose homeostasis.
How It Is Measured or Detected
Peroxisome proliferation-activated receptors are investigated by changes in gene expression and protein levels. X-ray crystallography can be used to determine molecular structure. Effects of PPAR gamma on expression of downstream genes can be investigating using metabolomics and RT-qPCR approaches.
Domain of Applicability
Life Stage: All life stages.
Sex: Applies to both males and females.
Taxonomic: Appears to be present broadly, with representative studies in mammals.
References
Ahmed, W., Ziouzenkova, O., Brown, J. Devchand, P. Francis, S., Kadakia, M., Kanda, T., Orasanu, G., Sharlach, M., Zandbergen, F., and Plutzky, J. 2007. PPARs and their metabolic modulation: new mechanisms for transcriptional regulation? Journal of Internal Medicine 262: 184-198.
Desvergne, B. and Wahli, W. 1999. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrine Reviews 20(5): 649-688.
Hihi, A.K., Michalik, L., Wahli, W. 2002. PPARs: transcriptional effectors of fatty acids and their derivatives. Cellular and Molecular Life Sciences 59: 790-798.