Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway

Aerobic exercise training promotes insulin sensitivity and skeletal muscle glycogen synthesis in HFD-fed rats. The beneficial effects of exercise might be mediated by EGR-1/PTP1B signaling pathway in skeletal muscle, however further studies are necessary to confirm this mechanism.

Sprague-Dawley rats fed a high-fat diet (HFD), and performed treadmill exercise training for 6-week. Oral glucose tolerance test was conducted to confirm the IR. Periodic Acid-Schiff (PAS) staining and anthrone colorimetry were used to assess the skeletal muscle glycogen. RT-qPCR, western blot, and immunofluorescence were used to detect the EGR-1/PTP1B pathway and associated signaling molecules.

Impaired skeletal muscle glycogen synthesis contributes to insulin resistance (IR). Aerobic exercise reported to ameliorate IR by augmenting insulin signaling, however the detailed mechanism behind this improvement remains unclear. This study investigated whether aerobic exercise enhances glycogen anabolism and insulin sensitivity via EGR-1/PTP1B signaling pathway in skeletal muscle of rats.

We found that exercise training significantly decreased blood glucose, insulin, and homeostasis model assessment for IR (HOMA-IR) against HFD-induced elevation. Decreased muscle glycogen content due to HFD was significantly restored after exercise training. Exercise training promoted mRNA expressions of Irs1, Akt, and Glut4, while inhibited Gsk-3β expression against HFD. Next, the decreased IRS1 (phosphorylated/total), AKT (phosphorylated/total), and GLUT4, and increased GSK-3β proteins with HFD were significantly reversed by exercise. Furthermore, HFD-induced overexpression of EGR-1 and PTP1B evidenced by mRNA, protein, and immunofluorescence intensity, were substantially inhibited by exercise, which may contribute to promote insulin sensitivity and glycogen anabolism. Conclusions: Aerobic exercise training promotes insulin sensitivity and skeletal muscle glycogen synthesis in HFD-fed rats. The beneficial effects of exercise might be mediated by EGR-1/PTP1B signaling pathway in skeletal muscle, however further studies are necessary to confirm this mechanism.