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Non-Hereditary Obesity Type Networks and New Drug Targets: An In Silico Approach.

Styliani A Geronikolou1,2, Athanasia Pavlopoulou3,4, Merve Uça Apaydin3,4

  • 1Clinical, Translational Research and Experimental Surgery Centre, Biomedical Research Foundation of the Academy of Athens, 4, Soranou Ephessiou Str., 11527 Athens, Greece.

International Journal of Molecular Sciences
|July 27, 2024
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This study maps gene networks in non-hereditary obesity, revealing stress and inflammation pathways. It identifies potential therapeutic targets and natural compounds for obesity treatment.

Keywords:
drug discoverykisspeptinnatural productsstress system/inflammation-induced obesitystress-induced obesitysystems epidemiology

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Area of Science:

  • Genetics and Systems Biology
  • Metabolic Disorders
  • Chronobiology

Background:

  • Obesity is a chronic, preventable disease with high societal costs due to comorbidities.
  • Understanding the pathogenesis of non-hereditary obesity is crucial for identifying therapeutic targets.
  • Biological clock genes play a role in energy balance and metabolic regulation.

Purpose of the Study:

  • To reconstruct interactomes of non-hereditary obesity to elucidate pathogenesis.
  • To identify potential therapeutic targets for obesity.
  • To discover natural compounds targeting obesity and circadian clock-associated proteins.

Main Methods:

  • Extracted obesity and biological-clock-related genes from PubMed, GeneCards, and OMIM.
  • Investigated gene/protein interactions using STRING v11.0 with a high confidence score (>0.7).
  • Applied virtual screening to identify natural compounds targeting relevant proteins.

Main Results:

  • Developed two interactomes: stress-induced (85 genes) and inflammation-induced (93 genes) obesidomes.
  • Identified 15 common genes between the two interactomes, including key metabolic and hormonal regulators (e.g., LEP, INS, MC4R).
  • Phelligridin E identified as a potential FOX1-DBD interaction blocker.

Conclusions:

  • Molecular networks provide insights into the integrated regulation of energy balance and obesity pathogenesis.
  • Findings may link chronopharmacology with natural products for novel obesity treatments.
  • Identified interactomes and compounds offer potential avenues for therapeutic intervention.