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.
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Date of publication: 30 July 2019; OECD Series on Adverse Outcome Pathways
Author information: Kurt A. Gust (1); Mitchell S. Wilbanks (1); Zachary A. Collier (1); Lyle D. Burgoon (1); & Edward J. Perkins (1)
(1) U.S. Army Engineer Research and Development Center