OECD Series on Adverse Outcome Pathways

An Adverse Outcome Pathway (AOP) describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure to a stressor and leads to an adverse health effect in humans or wildlife. AOPs are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. These AOPs are available in the AOP-Wiki, an interactive and virtual encyclopaedia for AOP development. Following their development and review, the endorsed AOPs are published in the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude regular updates or new contributions to a given AOP. While the AOP-Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP.


Adverse Outcome Pathway on antagonist binding to PPARα leading to body-weight loss

The present AOP describes antagonistic chemical binding to the peroxisome proliferator-activated receptor α (PPARα), resulting in preferential binding a co-repressor to the overall PPARα signalling complex causing a chain of events that includes: antagonism of PPARα nuclear signalling, decreased transcriptional expression of PPARα-regulated genes that support energy metabolism, inhibited metabolic energy production (decreased fatty acid beta oxidation and ketogenesis), and increase in catabolism of muscle protein, culminating with starvation-like weight loss. The AOP is likely to be synergised during fasting, starvation or malnutrition events. The adverse outcome of this AOP is body-weight loss, which within the context of dynamic energy budget theory, decreases energy allocations to organismal maturation and reproduction and has been demonstrated to negatively affect ecological fitness.


This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error