PMID- 38541736 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240330 IS - 2075-1729 (Print) IS - 2075-1729 (Electronic) IS - 2075-1729 (Linking) VI - 14 IP - 3 DP - 2024 Mar 20 TI - Aerobic Exercise Modulates Proteomic Profiles in Gastrocnemius Muscle of db/db Mice, Ameliorating Sarcopenia. LID - 10.3390/life14030412 [doi] LID - 412 AB - Type-2 diabetes mellitus (T2DM)-induced sarcopenia is intertwined with diminished insulin sensitivity and extracellular matrix (ECM) remodeling in skeletal muscle and other organs. Physical activities such as aerobic exercise play a crucial role in regulating blood glucose levels, insulin sensitivity, metabolic pathways, oxidative stress, fibrosis, ECM remodeling, and muscle regeneration by modulating differentially expressed protein (DEP) levels. The objectives of our research were to investigate the effect of six weeks of aerobic exercise on the gastrocnemius and soleus muscle of db/db mice's DEP levels compared to those of sedentary db/db mice. A total of eight db/db mice were divided into two groups (n = 4 per group), namely sedentary mice (SED) and exercise-trained mice (ET), of which the latter were subjected to six weeks of a moderate-intensity aerobic exercise intervention for five days per week. After the exercise intervention, biochemical tests, including analyses of blood glucose and HbA1c levels, were performed. Histological analysis using H & E staining on tissue was performed to compare morphological characters. Gastrocnemius and soleus muscles were dissected and processed for proteomic analysis. Data were provided and analyzed based on the DEPs using the label-free quantification (LFQ) algorithm. Functional enrichment analysis and Ingenuity Pathway Analysis (IPA) were employed as bioinformatics tools to elucidate the molecular mechanisms involved in the DEPs and disease progression. Significantly reduced blood glucose and HbA1c levels and an increased cross-sectional area (CSA) of gastrocnemius muscle fibers were seen in the ET group after the exercise interventions due to upregulations of metabolic pathways. Using proteomics data analysis, we found a significant decrease in COL1A1, COL4A2, ENG, and LAMA4 protein levels in the ET gastrocnemius, showing a significant improvement in fibrosis recovery, ECM remodeling, and muscle regeneration via the downregulation of the TGF-beta signaling pathway. Upregulated metabolic pathways due to ET-regulated DEPs in the gastrocnemius indicated increased glucose metabolism, lipid metabolism, muscle regeneration, and insulin sensitivity, which play a crucial role in muscle regeneration and maintaining blood glucose and lipid levels. No significant changes were observed in the soleus muscle due to the type of exercise and muscle fiber composition. Our research suggests that engaging in six weeks of aerobic exercise may have a positive impact on the recovery of T2DM-induced sarcopenia, which might be a potential candidate for mitigation, prevention, and therapeutic treatment in the future. FAU - Huang, Yen-Chun AU - Huang YC AD - Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan 333325, Taiwan. AD - Marker Exploration Corporation, Taipei 112022, Taiwan. FAU - Sanotra, Monika Renuka AU - Sanotra MR AD - Marker Exploration Corporation, Taipei 112022, Taiwan. AD - Department of Cardiology, Taipei Veterans General Hospital, Taipei 112201, Taiwan. FAU - Huang, Chi-Chang AU - Huang CC AUID- ORCID: 0000-0003-1446-6787 AD - Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan 333325, Taiwan. AD - Tajen University, Pingtung 907101, Taiwan. FAU - Hsu, Yi-Ju AU - Hsu YJ AD - Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan 333325, Taiwan. FAU - Liao, Chen-Chung AU - Liao CC AUID- ORCID: 0000-0002-6634-8355 AD - Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan. LA - eng GR - MOST110-2410-HA49A-514/Ministry of Science and Technology of Taiwan/ PT - Journal Article DEP - 20240320 PL - Switzerland TA - Life (Basel) JT - Life (Basel, Switzerland) JID - 101580444 PMC - PMC10971967 OTO - NOTNLM OT - ECM remodeling OT - T2DM-induced sarcopenia OT - aerobic exercise OT - db/db mice OT - gastrocnemius muscle OT - metabolic pathways OT - muscle regeneration OT - proteomic profiling COIS- Authors Yen-Chun Huang and Monika Renuka Sanotra were employed by the company Marker Exploration Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/03/28 06:45 MHDA- 2024/03/28 06:46 PMCR- 2024/03/20 CRDT- 2024/03/28 01:15 PHST- 2024/02/07 00:00 [received] PHST- 2024/03/15 00:00 [revised] PHST- 2024/03/15 00:00 [accepted] PHST- 2024/03/28 06:46 [medline] PHST- 2024/03/28 06:45 [pubmed] PHST- 2024/03/28 01:15 [entrez] PHST- 2024/03/20 00:00 [pmc-release] AID - life14030412 [pii] AID - life-14-00412 [pii] AID - 10.3390/life14030412 [doi] PST - epublish SO - Life (Basel). 2024 Mar 20;14(3):412. doi: 10.3390/life14030412.