Epigenetic regulation of miR-211 in the hypothalamic arcuate nucleus of female rats during diet-induced obesity and caloric restriction.

Abstract

Epigenetic modifications dynamically regulate gene expression in response to environmental factors. miR-211 has been implicated in hypothalamic regulation of energy homeostasis. This study investigates the epigenetic regulation of miR-211 in the arcuate nucleus (ARC) of female Wistar rats during diet-induced obesity (DIO) and caloric restriction (CR). Female Wistar rats were subjected to a DIO protocol followed by CR. miR-211 expression was measured in the ARC, and two epigenetic layers-histone methylation (H3K9me2 enrichment) and CpG DNA methylation-were analyzed at the miR-211 promoter. Aml1/Runx1 binding was assessed via chromatin immunoprecipitation. DIO upregulated miR-211 expression in the ARC, while CR restored it to baseline levels. Increased H3K9me2 enrichment at the miR-211 promoter during DIO was reversed by CR. CpG methylation analysis revealed hypermethylation at the miR-211 promoter, particularly at -78 CpG, during DIO, which partially reverted after CR. Hyper-methylation in DIO was associated with reduced Aml1/Runx1 binding, suggesting a loss of transcriptional repression. Blood samples showed a similar CpG methylation pattern, indicating potential biomarker applications. In conclusion, miR-211 expression in the ARC is regulated by histone and DNA methylation in response to metabolic status. The reversal of these epigenetic changes by CR highlights the potential of lifestyle interventions to mitigate obesity-induced molecular alterations. These findings provide insights into miR-211's role in hypothalamic dysregulation and its potential as a therapeutic target for obesity management.