Aerobic exercise modulates noncoding RNA network upstream of FNDC5 in the Gastrocnemius muscle of high-fat-diet-induced obese mice

The purpose of the study was to determine the influence of aerobic exercise with a fat-rich diet on ncRNAs expression associated with FNDC5 in the Gastrocnemius muscle of the obese mice. Twenty-five male mice were grouped into two categories of normal diet (ND) and high-fat diet (HF) treatments for three months. For the subsequent treatment, HF-fed animals (obese) were proceeded in four groups: HF-Trained (n = 5), HF-Untrained (n = 5), ND-Trained (n = 5), and ND-Untrained (n = 5). Simultaneously, ND fed mice (n = 5) continued receiving normal diet and being untrained. In the training group, exercise was applied using a treadmill for 2 months. The Gastrocnemius muscle was excised for the assessment of FNDC5 mRNA, protein levels, and ncRNAs. Using bioinformatics tools, two potential miRNAs, miR-129-5p and miR-140-5p, and four lncRNAs constructing a network with FNDC5 were identified. Significant decrease was observed in both miR-129-5p and miR-140-5p in the HF-fed mice vs. ND-fed mice (p < 0.01). Significant increase of lncRNAs Meg3, Malat1, Neat1, and Kcnq1ot1 correlating in the network was also detected (p < 0.001 for all lncRNAs) in HF-fed mice and trained mice (p < 0.001 for Neat1, Meg3, and Kcnq1ot1). The present study suggests that an increase in the muscle FNDC5 of the high-fat diet mice is governed by an expression regulation of suggested ncRNAs, which were revealed by bioinformatics study to be involved in the insulin resistance and glucose homeostasis pathways.

Automated summary

The study found significant effects of aerobic exercise with a fat-rich diet on ncRNAs expression associated with FNDC5 in the Gastrocnemius muscle of obese mice. Bioinformatics analysis identified miR-129-5p, miR-140-5p, and four lncRNAs constructing a network with FNDC5. Changes in the expression levels of these ncRNAs were suggested to be involved in insulin resistance and glucose homeostasis pathways in high-fat diet mice.