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

Author

Listed:
  • Kurt A. Gust

    (U.S. Army Engineer Research and Development Center)

  • Mitchell S. Wilbanks

    (U.S. Army Engineer Research and Development Center)

  • Zachary A. Collier

    (U.S. Army Engineer Research and Development Center)

  • Lyle D. Burgoon

    (U.S. Army Engineer Research and Development Center)

  • Edward J. Perkins

    (U.S. Army Engineer Research and Development Center)

Abstract

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.

Suggested Citation

  • Kurt A. Gust & Mitchell S. Wilbanks & Zachary A. Collier & Lyle D. Burgoon & Edward J. Perkins, 2019. "Adverse Outcome Pathway on antagonist binding to PPARα leading to body-weight loss," OECD Series on Adverse Outcome Pathways 10, OECD Publishing.
    • Handle: RePEc:oec:envaad:10-en
    DOI: 10.1787/29d4e08d-en
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