Event:227
Contents
Event Title
Key Event Overview
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AOPs Including This Key Event
Chemical Initiators
The following are chemical initiators that operate through this AOP:
Taxonomic Applicability
Name | Scientific Name | Evidence | Links |
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rat | Rattus sp. | Strong | NCBI |
Level of Biological Organization
Biological Organization |
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Molecular |
How this Key Event works
Biological state
The Peroxisome Proliferator Activated receptor α (PPAR α) belongs to Peroxisome Proliferator Activated receptors (PPARs; NR1C) steroid/thyroid/retinoid receptor superfamily of transcription factors.
Biological compartments
PPARα is expressed in high levels in tissues that perform significant catabolism of fatty acids (FAs), such as brown adipose tissue, liver, heart, kidney, and intestine (Michalik et al., 2006). The receptor is present in also in skeletal muscle, intestine, pancreas, lung, placenta (Mukherjee et al., 1997).
General role in biology
PPARs are activated by fatty acids and their derivatives; they are sensors of dietary lipids and are involved in lipid and carbohydrate metabolism; immune response and peroxisome proliferation (Wahli and Desvergne 1999), (Evans, Barish, & Wang, 2004). PARα is a also a target of hypothalamic hormone signalling and was found to play a role in embryonic development (Yessoufou and Wahli 2010).
Fibrates, activators of PPAR𝛼, are commonly used to treat hypertriglyceridemia and other dyslipidemic states as they have been shown to decrease circulating lipid levels (Lefebvre et al. 2006).
How it is Measured or Detected
Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?