Exercise activates autophagy and regulates endoplasmic reticulum stress in muscle of high-fat diet mice to alleviate insulin resistance

• DOI: 10.1016/j.bbrc.2022.02.058
• Publication Date: 2022-02-22T00:12:32Z
• Authors: Fangzhou Cheng; Yaoshan Dun; Jing Cheng; Jeffrey W. Ripley...; Wenlong Jiang; Baiyang You; Suixin Liu
• Keywords: Mice, Inbred C57BL; 0301 basic medicine; Mice; 03 medical and health sciences; Autophagy; Animals; AMP-Activated Protein Kinases; Insulin Resistance; Diet, High-Fat; Endoplasmic Reticulum Stress; Muscle, Skeletal; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

Exercise training has been demonstrated as an effective therapy for insulin resistance (IR) to relieve skeletal muscle metabolic disorders. Physiologic protective autophagy was found blocked by IR induced severe endoplasmic reticulum (ER) stress, which may lead to progression of IR. However, the mechanisms are not fully understood. Therefore, this study sought to investigate that how exercise training act on IR through an exploration into the mechanism of ER stress and high-fat diet (HFD)-blocked autophagy. A rodent model was adopted in mice via a HFD and an 8-week swim exercise training intervention. The mouse IR model was successfully established through HFD treatment: body mass, adipose weight, HOMA-IR index increased, as well as IRS1, inhibited in the muscle of HFD mice. Moreover, the AMPK/PGC1α pathway was depressed and IRE1, PERK, ATF6-related ER stress signaling was activated in the muscle of HFD mice. While autophagy factors, including BNIP3, LC3II/LC3I, and PINK1, decreased. However, additional 8-week exercise training during HFD was found to reverse all these changes and alleviate IR. Thus, exercise training could facilitate HFD-blocked protective autophagy via the activation of the AMPK/PGC1α pathway to relieve insulin resistance in mice. Our study provides experimental data for the prevention of T2DM and insulin resistance.