Exercise rescues aberrantly expressed genes in diet-induced obese rats: a potential role of miR-211 modulation in the hypothalamic arcuate nucleus
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. The purpose of this study was to examine the mechanism by which aberrantly expressed genes in the hypothalamic arcuate nucleus (ARC) of diet-induced obese (DIO) rats is attenuated through voluntary exercise. Methods: A transcriptomic approach assessed novel genes in the ARC that affect DIO by voluntary wheel running and a combined approach of physiology, pharmacology, transcriptomic and bioinformatics analysis were used to evaluate the role of miR in the reversal of obesity. Results: Exercise attenuated body weight gain, decreased fat mass, and restored gene expression in the ARC. As high-fat diet (HFD) consumption can cause dysregulation of satiety/hunger regulation mechanisms in the ARC, we outlined transcriptional clusters which depicted alterations in patterns of gene expression through running. Among them were genes involved with inflammation and cellular structure. To uncover regulatory mechanisms governing gene expression in DIO attenuation, we explored the role of miR-211, as it has been implicated in systemic inflammation. The DIO overexpression of miR-211 was ameliorated by exercise, demonstrating its pivotal role in the regulation of inflammation in the ARC. Further, in vivo central administration of miR-211-mimic affected the expression of immunity and cell cycle related genes. By comparing genes attenuated by running and genes downregulated by miR-211, we produced a list of candidate genes that might be involved in the modulation by miR-211 in attenuating obesity by exercise. Conclusion: This research suggests that exercise may have a rescue effect on obesity through changes in gene expression that are mediated partially though miR-211. Overall design: Comparative gene expression profiling analysis of RNA-seq data for the arcuate nucleus of Wisat rats that were either i) chow fed/sedentary, ii) diet-induced obesity (HF fed)/sedentary, iii) diet-induced obese/volunray wheel running, iv) injected with MiRIDIAN hsa-miR-211-mimic, v) injected with MiRIDIAN hsa-miR-211-hairpin inhibitor