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Multi-omics study on the effect of moderate intensity exercise on protein of lactylation in mouse muscle tissue

ABSTRACT: To explore the effects of moderate intensity exercise on protein of lactylation in mouse muscle tissue metabolism. The healthy adult mice running for 6 weeks as exercise model and sedentary mice as control were used to perform transcriptomic, proteomic, lactylation-proteomics, and metabolomics analysis. In addition, correlation analysis between transcriptome and proteome, and proteome and metabolome was conducted as well. In this study, 159 lactate sites of 78 proteins were identified to be differentically regulated by moderate intensity exercise. Enrichment analysis showed that lactated proteins Mtatp8, Atp5mg and Atp5po exhibited ATP hydrolysis activity. They are involved in biological processes such as mitochondrial transmembrane transport, and Mtatp8, Atp5mg and Atp5po participate in Oxidative phosphorylation and Thermogenesis pathways. The lactation levels of Mtatp8, Atp5mg and Atp5po proteins in exercise group were significantly decreased, while their protein levels were significantly increased. The combined analysis of proteomics and metabolomics showed that the Oxocarboxylic acid metabolism pathway and Sphingolipid signaling pathway had significant changes under the influence of moderate intensity exercise. Our results showed that moderate intensity exercise has a certain effect on the lactylation level of mice, possibly by reducing lactylation levels of Mtatp8, Atp5mg and Atp5po and increasing the expression of their protein levels, thereby regulating the Oxidative phosphorylation pathway and participating in energy metabolism. 2-Oxocarboxylic acid metabolism pathway and Sphingolipid signaling pathway need to be further explored.

INSTRUMENT(S): timsTOF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Leg Muscle

SUBMITTER: Wanyu Wu

LAB HEAD: Jiahui Chang, Wanyu Wu, Ping Qian, Zhaoxu Lu, Xuejia He, Fang Wang, Ting Zhang

PROVIDER: PXD053276 | Pride | 2025-02-10

REPOSITORIES: Pride

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			Action	DRS
	XA04524B2LPLa_Con_1_Slot2-7_1_21842.d.zip	Other
	XA04524B2LPLa_Con_2_Slot2-8_1_21844.d.zip	Other
	XA04524B2LPLa_Con_3_Slot2-9_1_21846.d.zip	Other
	XA04524B2LPLa_EX_1_Slot2-10_1_21848.d.zip	Other
	XA04524B2LPLa_EX_2_Slot2-11_1_21850.d.zip	Other

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Project description:The hippocampal proteins obtained from both exercised (moderate-intensity running for 6 weeks) and sedentary mice were separately analyzed for Liquid chromatography–tandem mass spectrometry (LC-MS/MS) identification with three replications. Acetylome data identified 3876 acetyl sites and 1764 acetylated proteins, which constituted 31% of the whole hippocampal proteome (totally 5725 proteins identified). In addition, 1305 proteins with 2769 acetyl sites were quantified. When defining the cutoffs for the fold change in abundance of 1.5 and P value < 0.05, 272 acetyl sites on 252 proteins were differentially regulated between exercise and control mice. Analysis of the subcellular localization showed that these differentially acetylated proteins (DAPs) exert different functions in multiple compartments, including the cytoplasm, mitochondria, nucleus and plasma membrane. The 19 up-regulated acetylated proteins mainly resided in mitochondria, while the 253 down-regulated DAPs were most abundant in cytoplasm, and the annotation of molecular functions were significantly enriched in catalytic activity and binding, respectively. Gene Ontology (GO) analysis showed that DAPs were primarily correlated with cytoskeleton, myelin sheath and axons in the cellular component category; and actin cytoskeleton organization, regulation of protein polymerization or depolymerization, and hexose/glucose metabolic process were significantly enriched in the biological process category. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DAPs were involved in central carbon metabolism, neurodegeneration diseases, synapses, and various signaling pathways. Among them, chronic exercise induced significant alterations in phototransduction, carbon-related metabolism (carbohydrate digestion and absorption, glycolysis/gluconeogenesis, fructose and mannose metabolism, and pyruvate metabolism) and Hippo signaling pathway. Meanwhile, 21 proteins were significantly expressed, which were enriched in the pathway of complement and coagulation cascades.

Project description:This file describes the SBML version of the mathematical model in the following journal article: Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise, Ann Biomed Eng. 2007 Jun;35(6):956-69. (Pubmed ID: 17380394). This mathematical model simulates oxygen transport and metabolism in skeletal muscle in response to a step change from a warm-up steady state to a higher work rate corresponding to exercise at different levels of intensity: moderate (M), heavy (H) and very heavy (VH). The model parameter values are listed in the tables of this article. The parameter values that are independent of the exercise level are reported in Table 2. The parameter values that depend on the exercise level are reported in Tables 1A, 3 and 4. The model simulations (Figures 2, 3, 4 and 5) were obtained for a representative subject with a set of parameter values different from those in Table 1A, 3 and 4. In the sbml model, these model parameters are used to simulate exercise at a very heavy (VH) intensity for the representative subject. Additionally, the parameter values needed to simulate exercise at moderate (M) and heavy (H) intensity are reported in the list of parameters of the file. The model simulates dynamics of (1) the concentrations of free (F) and total (T) oxygen concentration in blood (CFcap, CTcap) and tissue (CFtis, CTtis), Adenosine Triphosphate (ATP), Adenosine Diphosphate (ADP), Phosphocreatine (PCr) and Creatine (Cr); (2) the metabolic flux of oxidative phosphorylation, creatine kinase and ATPase; (3) the oxygen uptake in blood and oxygen transport rate from blood to tissue during exercise. The simulation also computes muscle oxygen saturation (StO2m) and relative muscle oxygen saturation (RStO2m) in order to compare simulated and experimental responses of human muscle oxygenation during exercise. The model was successfully tested with Roadrunner of the Systems Biology Workbench (SBW). The model simulations obtained with Roadrunner match those obtained with the mathematical model represented in Fortran and Matlab for relative and absolute tolerance smaller than 10-7. To allow for simulations at varying levels of exercise, the parameter exercise_level was introduced. A value of 1 means medium, 2 heavy and 3 very heavy exercise. Setting this parameter assigns the parameters Vmax, KatpaseE, dQMm and tauQm with the relevant parameters. The warmup steady state is influenced by the parameter changes for this representative subject and the model has to be brought into steady state after each change of exercise level. This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Nov��re N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

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Multi-omics study on the effect of moderate intensity exercise on protein of lactylation in mouse muscle tissue

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