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

J Physiol Biochem. 2021 Nov;77(4):589-600. doi: 10.1007/s13105-021-00825-w. Epub 2021 Aug 18.

Abstract

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.

Keywords: High-fat diet; Kcnq1ot1; Malat1; Meg3; MiR-129-5p; MiR-140-5p; Neat1.

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects
  • Fibronectins
  • Insulin Resistance*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • MicroRNAs* / genetics
  • Muscle, Skeletal
  • RNA, Long Noncoding* / genetics

Substances

  • FNDC5 protein, mouse
  • Fibronectins
  • MicroRNAs
  • RNA, Long Noncoding