Event:227

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Event Title

PPARα, Activation
Short name: PPARα, Activation

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
PPAR alpha activation leading to decreased fertility upon utero exposure in rodent males MIE Weak
PPARα activation leading to impaired fertility in adult male rodents MIE Weak
NFE2L2/FXR activation leading to hepatic steatosis KE

Chemical Initiators

The following are chemical initiators that operate through this AOP:

  1. Di(2-ethylhexyl) phthalate
  2. Mono(2-ethylhexyl) phthalate


Taxonomic Applicability

Name Scientific Name Evidence Links
rat Rattus sp. Strong NCBI

Level of Biological Organization

Biological Organization
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?

Evidence Supporting Taxonomic Applicability

Evidence for Chemical Initiation of this Molecular Initiating Event

References