Systematic Analysis of Molecular Mechanisms of Exercise in Regulating Cholesterol Biosynthesis: Molecular Network Modeling for Therapeutic Target Identification

Document Type : Research Paper

Authors
1 Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan
2 sport physiology,sport science,esfahan univercity,esfahan,iran
3 Royan Institute of Biotechnology, Isfahan
4 "Royan Institute of Biotechnology, Isfahan
Abstract
Objectives: The regulation of cholesterol biosynthesis is a complex and highly controlled process involving a network of genes that coordinate the synthesis, regulation, and homeostasis of cholesterol levels. This study examines several key genes such as Idi1, Fdps, Sqle, Hmgcs1, and others, which play fundamental roles in cholesterol biosynthesis, lipid metabolism, and cellular signaling. Materials and Methods: Computational modeling of these regulatory networks can reveal the intricate interactions among these genes and their regulatory mechanisms under various conditions, including high-fat diets. Our bioinformatics analysis evaluates the impact of high-fat diets and exercise on these genes, exploring the dynamic regulation of cholesterol biosynthesis pathways and their adjustability. Additionally, identifying novel drug targets, such as microRNAs, may lead to innovative therapeutic strategies for managing dyslipidemia. By integrating systems biology approaches with computational tools, this study aims to enhance our understanding of cholesterol metabolism and identify the effects of physical exercise and novel drug interventions on lipid disorders. Results: Cholesterol biosynthesis pathways were analyzed using transcriptomic data, and hub genes involved in these pathways were identified. Network clustering analysis corroborated the results of GO and KEGG analyses. Conclusion: This study provides a list of hub genes, critical pathways, and novel insights for developing strategies to manage cholesterol biosynthesis while shedding light on the fundamental mechanisms underlying liver responses.
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Articles in Press, Accepted Manuscript
Available Online from 02 August 2025

  • Receive Date 23 March 2025
  • Revise Date 22 June 2025
  • Accept Date 04 July 2025