Exercise Rescues Obesogenic-Related Genes in the Female Hypothalamic Arcuate Nucleus: A Potential Role of miR-211 Modulation

Kayla Rapps, Asaf Marco, Hilla Pe’er-Nissan, Tatiana Kisliouk, Gabrielle Stemp, Gal Yadid, Aron Weller, Noam Meiri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Obesity is a major public health concern that is associated with negative health outcomes. Exercise and dietary restriction are commonly recommended to prevent or combat obesity. This study investigates how voluntary exercise mitigates abnormal gene expression in the hypothalamic arcuate nucleus (ARC) of diet-induced obese (DIO) rats. Using a transcriptomic approach, novel genes in the ARC affected by voluntary wheel running were assessed alongside physiology, pharmacology, and bioinformatics analysis to evaluate the role of miR-211 in reversing obesity. Exercise curbed weight gain and fat mass, and restored ARC gene expression. High-fat diet (HFD) consumption can dysregulate satiety/hunger mechanisms in the ARC. Transcriptional clusters revealed that running altered gene expression patterns, including inflammation and cellular structure genes. To uncover regulatory mechanisms governing gene expression in DIO attenuation, we explored miR-211, which is implicated in systemic inflammation. Exercise ameliorated DIO overexpression of miR-211, demonstrating its pivotal role in regulating inflammation in the ARC. Further, in vivo central administration of miR-211-mimic affected the expression of immunity and cell cycle-related genes. By cross-referencing exercise-affected and miR-211-regulated genes, potential candidates for obesity reduction through exercise were identified. This research suggests that exercise may rescue obesity through gene expression changes mediated partially through miR-211.

Original languageEnglish
Article number7188
JournalInternational Journal of Molecular Sciences
Volume25
Issue number13
DOIs
StatePublished - Jul 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • diet-induced obesity
  • epigenetics
  • gene expression
  • hypothalamus
  • micro-RNA
  • obesity
  • voluntary exercise

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