Jiwon Shin (Department of Biological Sciences, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 34141, Republic of Korea)

Jeong Hee Moon (Core Research Facility & Analysis Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea)

Hyeonwoo Kim (Department of Biological Sciences, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 34141, Republic of Korea)

Jiwon Shin (Department of Biological Sciences, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 34141, Republic of Korea)

Ga Seul Lee (Core Research Facility & Analysis Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea/College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea)

Junseo Ha (Department of Biological Sciences, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 34141, Republic of Korea)

Jeong Hee Moon (Core Research Facility & Analysis Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea)

Hyeonwoo Kim (Department of Biological Sciences, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 34141, Republic of Korea)

Exercise represents a major challenge to whole-body homeostasis provoking widespread perturbations in numerous organs. Skeletal muscle, a primary-responding organ, displays remarkable adaptation plasticity with exercise-induced increases in metabolic activities with increased beta-oxidation levels. Especially, highly active athletes possess a greater number of smaller intramyocellular lipid droplets (IMCL) without significant changes in insulin sensitivity compared to type II diabetic patients with insulin insensitivity. During the past decade, it has also been confirmed as an endocrine organ, releasing cytokines and other peptides, called myokines. These findings of inter-organ crosstalk, shed light on a framework for understanding how exercise mediates many of its beneficial systemic changes and leads to muscle adaptation.

However, the regulation of skeletal muscle proteome itself and secretome, especially lipid metabolic pathway during exercise is still elusive. Here, we used an electrical pulse stimulation system, a useful method to partially mimic exercise by inducing contractions in cultured mouse-driven skeletal muscle C2C12 cells in vitro. To investigate how muscle cells and their secreted factors change with this electric stimulation or with an exogenous fatty acid source, LC-MS/MS-based proteomic comparisons were performed, showing distinguishable pivotal pathways and molecules among groups. In conclusion, exercise-like properties can be captured with these certain molecules, which give therapeutic insights for patients with musculoskeletal inabilities, metabolic disorders, and even neuropathology.