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

Abstract Objective 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...

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Main Authors: Liangzhi Zhang, Xiaojie Liu, Jing Hu, Helong Quan, Sang Ki Lee, Mallikarjuna Korivi, Lifeng Wang, Ting Li, Wei Li
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Nutrition & Metabolism
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Online Access:https://doi.org/10.1186/s12986-024-00888-8
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author Liangzhi Zhang
Xiaojie Liu
Jing Hu
Helong Quan
Sang Ki Lee
Mallikarjuna Korivi
Lifeng Wang
Ting Li
Wei Li
author_facet Liangzhi Zhang
Xiaojie Liu
Jing Hu
Helong Quan
Sang Ki Lee
Mallikarjuna Korivi
Lifeng Wang
Ting Li
Wei Li
author_sort Liangzhi Zhang
collection DOAJ
description Abstract Objective 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. Methods 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. Results 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.
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publishDate 2024-12-01
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spelling doaj-art-6cbdd1b11a4e47d9aae2769cddf0fc492025-01-05T12:10:29ZengBMCNutrition & Metabolism1743-70752024-12-0121111310.1186/s12986-024-00888-8Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathwayLiangzhi Zhang0Xiaojie Liu1Jing Hu2Helong Quan3Sang Ki Lee4Mallikarjuna Korivi5Lifeng Wang6Ting Li7Wei Li8College of Physical Education and Health Sciences, Zhejiang Normal UniversityCollege of Physical Education and Health Sciences, Zhejiang Normal UniversityDepartment of Clinical Medicine, Medical College, Jinhua University of Vocational TechnologyExercise Capacity Assessment and Promotion Research Center, School of Physical Education, Northeast Normal UniversityDepartment of Sport Science, College of Natural Science, Chungnam National UniversityCollege of Physical Education and Health Sciences, Zhejiang Normal UniversityCollege of Physical Education and Health Sciences, Zhejiang Normal UniversityCollege of Physical Education and Health Sciences, Zhejiang Normal UniversityCollege of Physical Education and Health Sciences, Zhejiang Normal UniversityAbstract Objective 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. Methods 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. Results 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.https://doi.org/10.1186/s12986-024-00888-8GlycometabolismInsulin sensitivityTreadmill runningGlycogen synthesisGLUT4IRS1
spellingShingle Liangzhi Zhang
Xiaojie Liu
Jing Hu
Helong Quan
Sang Ki Lee
Mallikarjuna Korivi
Lifeng Wang
Ting Li
Wei Li
Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway
Nutrition & Metabolism
Glycometabolism
Insulin sensitivity
Treadmill running
Glycogen synthesis
GLUT4
IRS1
title Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway
title_full Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway
title_fullStr Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway
title_full_unstemmed Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway
title_short Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway
title_sort aerobic exercise attenuates high fat diet induced glycometabolism impairments in skeletal muscle of rat role of egr 1 ptp1b signaling pathway
topic Glycometabolism
Insulin sensitivity
Treadmill running
Glycogen synthesis
GLUT4
IRS1
url https://doi.org/10.1186/s12986-024-00888-8
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