[en] Skeletal muscle is a highly plastic organ that adapts to different metabolic states or functional demands. This study explored the impact of permanent glucose restriction (GR) on skeletal muscle composition and metabolism. Using Glut4m mice with defective glucose transporter 4, we conducted multi-omics analyses at different ages and after low-intensity treadmill training. The oxidative fibers were significantly increased in Glut4m muscles. Mechanistically, GR activated AMPK pathway, promoting mitochondrial function and beneficial myokine expression, and facilitated slow fiber formation via CaMK2 pathway. Phosphorylation-activated Perm1 may synergize AMPK and CaMK2 signaling. Besides, MAPK and CDK kinases were also implicated in skeletal muscle protein phosphorylation during GR response. This study provides a comprehensive signaling network demonstrating how GR influences muscle fiber types and metabolic patterns. These insights offer valuable data for understanding oxidative fiber formation mech- anisms and identifying clinical targets for metabolic diseases.
Research Center/Unit :
TERRA Research Centre. Ingénierie des productions animales et nutrition - ULiège State Key Laboratory of Animal Biotech Breeding. Institute of Animal Science, Chinese Academy of Agricultural Sciences
Precision for document type :
Analysis of case law/Statutory reports
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Zhang, Kaiyi ; Université de Liège - ULiège > TERRA Research Centre ; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Xie, Ning; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Ye, Huaqiong; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Miao, Jiakun; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Xia, Boce; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Yang, Yu; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Peng, Huanqi; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Xu, Shuang; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Wu, Tianwen; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Tao, Cong; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Ruan, Jinxue; Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, China
Wang, Yanfang; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China
Yang, Shulin; State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China ; Cell Signaling Technology
National Key Research and Development Program of China
Funders :
CSC - China Scholarship Council NSCF - National Natural Science Foundation of China
Funding text :
This research was funded by The National Key R&D Program of China (2021YFA0805903), The National Natural Science Foundation of China (grant no. 32070535), The Agricultural Science and Technology Innovation Program (grant no. ASTIP-IAS05) and China Scholarship Council (file number: 202203250093, K.Z.).
Smith, R.L., Soeters, M.R., Wüst, R.C.I., Houtkooper, R.H., Metabolic flexibility as an adaptation to energy resources and requirements in health and disease. Endocr. Rev. 39 (2018), 489–517.
Goodpaster, B.H., Sparks, L.M., Metabolic flexibility in health and disease. Cell Metab. 25 (2017), 1027–1036.
Kruse, R., Højlund, K., Proteomic study of skeletal muscle in obesity and type 2 diabetes: progress and potential. Expert Rev. Proteomics 5 (2018), 817–828.
Bareja, A., Draper, J.A., Katz, L.H., Lee, D.E., Grimsrud, P.A., White, J.P., Chronic caloric restriction maintains a youthful phosphoproteome in aged skeletal muscle. Mech. Ageing Dev., 195, 2021, 111443.
Egan, B., Zierath, J.R., Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. 17 (2013), 162–184.
Petriz, B.A., Gomes, C.P., Almeida, J.A., de Oliveira, G.P. Jr., Ribeiro, F.M., Pereira, R.W., Franco, O.L., The effects of acute and chronic exercise on skeletal muscle proteome. J. Cell. Physiol. 232 (2017), 257–269.
Zhang, L., Lv, J., Wang, C., Ren, Y., Yong, M., Myokine, a key cytokine for physical exercise to alleviate sarcopenic obesity. Mol. Biol. Rep. 50 (2022), 2723–2734.
Jodeiri Farshbaf, M., Alviña, K., Multiple roles in meuroprotection for the exercise derived myokine irisin. Front. Aging Neurosci., 13, 2021, 649929.
Vinel, C., Lukjanenko, L., Batut, A., Deleruyelle, S., Pradère, J.P., Le Gonidec, S., Dortignac, A., Geoffre, N., Pereira, O., Karaz, S., et al. The exerkine apelin reverses age-associated sarcopenia. Nat. Med. 24 (2018), 1360–1371.
Narkar, V.A., Downes, M., Yu, R.T., Embler, E., Wang, Y.X., Banayo, E., Mihaylova, M.M., Nelson, M.C., Zou, Y., Juguilon, H., et al. AMPK and PPARdelta agonists are exercise mimetics. Cell 134 (2008), 405–415.
Thomson, D.M., The Role of AMPK in the regulation of skeletal muscle size, hypertrophy, and regeneration. Int. J. Mol. Sci., 19, 2018, 3125.
Murphy, R.M., Watt, M.J., Febbraio, M.A., Metabolic communication during exercise. Nat. Metab. 2 (2020), 805–816.
Mu, X., Brown, L.D., Liu, Y., Schneider, M.F., Roles of the calcineurin and CaMK signalling pathways in fast-to-slow fibre type transformation of cultured adult mouse skeletal muscle fibres. Physiol. Genomics 30 (2007), 300–312.
Richter, E.A., Hargreaves, M., Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol. Rev. 93 (2013), 993–1017.
Sun, L., Zeng, X., Yan, C., Sun, X., Gong, X., Rao, Y., Yan, N., Crystal structure of a bacterial homologue of glucose transporters GLUT1-4. Nature 490 (2012), 361–366.
Deng, D., Xu, C., Sun, P., Wu, J., Yan, C., Hu, M., Yan, N., Crystal structure of the human glucose transporter GLUT1. Nature 510 (2014), 121–125.
Deng, D., Sun, P., Yan, C., Ke, M., Jiang, X., Xiong, L., Ren, W., Hirata, K., Yamamoto, M., Fan, S., et al. Molecular basis of ligand recognition and transport by glucose transporters. Nature 526 (2015), 391–396.
Ernst, J., Bar-Joseph, Z., STEM: a tool for the analysis of short time series gene expression data. BMC Bioinf., 7, 2006, 191.
Melgar, S., Bjursell, M., Gerdin, A.K., Svensson, L., Michaëlsson, E., Bohlooly-Y, M., Mice with experimental colitis show an altered metabolism with decreased metabolic rate. Am. J. Physiol. Gastrointest. Liver Physiol. 292 (2007), G165–G172.
Subbotina, E., Sierra, A., Zhu, Z., Gao, Z., Koganti, S.R., Reyes, S., Stepniak, E., Walsh, S.A., Acevedo, M.R., Perez-Terzic, C.M., et al. Musclin is an activity-stimulated myokine that enhances physical endurance. Proc. Natl. Acad. Sci. USA 112 (2015), 16042–16047.
Guo, S., Huang, Y., Zhang, Y., Huang, H., Hong, S., Liu, T., Impacts of exercise interventions on different diseases and organ functions in mice. J. Sport Health Sci. 9 (2020), 53–73.
Caenepee, l S., Charydczak, G., Sudarsanam, S., Hunter, T., Manning, G., The mouse kinome: discovery and comparative genomics of all mouse protein kinases. Proc. Natl. Acad. Sci. USA 101 (2004), 11707–11712.
Metz, K.S., Deoudes, E.M., Berginski, M.E., Jimenez-Ruiz, I., Aksoy, B.A., Hammerbacher, J., Gomez, S.M., Phanstiel, D.H., Coral: clear and customizable visualization of human kinome data. Cell Syst 7 (2018), 347–350.e1.
Tsao, T.S., Stenbit, A.E., Factor, S.M., Chen, W., Rossetti, L., Charron, M.J., Prevention of insulin resistance and diabetes in mice heterozygous for GLUT4 ablation by transgenic complementation of GLUT4 in skeletal muscle. Diabetes 48 (1999), 775–782.
Galuska, D., Ryder, J., Kawano, Y., Charron, M.J., Zierath, J.R., Insulin signalling and glucose transport in insulin resistant skeletal muscle. Special reference to GLUT4 transgenic and GLUT4 knockout mice. Adv. Exp. Med. Biol. 441 (1998), 73–85.
Zisman, A., Peroni, O.D., Abel, E.D., Michael, M.D., Mauvais-Jarvis, F., Lowell, B.B., Wojtaszewski, J.F., Hirshman, M.F., Virkamaki, A., Goodyear, L.J., et al. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat. Med. 6 (2000), 924–928.
Carvalho, E., Kotani, K., Peroni, O.D., Kahn, B.B., Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle. Am. J. Physiol. Endocrinol. Metab. 289 (2005), E551–E561.
Højlund, K., Metabolism and insulin signalling in common metabolic disorders and inherited insulin resistance. Dan. Med. J., 61, 2014, B4890.
Qi, Y., Zhang, X., Seyoum, B., Msallaty, Z., Mallisho, A., Caruso, M., Damacharla, D., Ma, D., Al-Janabi, W., Tagett, R., et al. Kinome profiling reveals abnormal activity of kinases in skeletal muscle from adults with obesity and insulin resistance. J. Clin. Endocrinol. Metab. 105 (2020), 644–659.
Severinsen, M.C.K., Pedersen, B.K., Muscle-organ crosstalk: the emerging roles of myokines. Endocr. Rev. 41 (2020), 594–609.
Karlsson, L., González-Alvarado, M.N., Motalleb, R., Wang, Y., Wang, Y., Börjesson, M., Zhu, C., Kuhn, H.G., Constitutive PGC-1α overexpression in skeletal muscle does not contribute to exercise-induced neurogenesis. Mol. Neurobiol. 58 (2021), 1465–1481.
Banzet, S., Koulmann, N., Sanchez, H., Serrurier, B., Peinnequin, A., Bigard, A.X., Musclin gene expression is strongly related to fast-glycolytic phenotype. Biochem. Biophys. Res. Commun. 353 (2007), 713–718.
Chen, W.J., Liu, Y., Sui, Y.B., Yang, H.T., Chang, J.R., Tang, C.S., Qi, Y.F., Zhang, J., Yin, X.H., Positive association between musclin and insulin resistance in obesity: evidence of a human study and an animal experiment. Nutr. Metab., 14, 2017, 46.
Shimomura, M., Horii, N., Fujie, S., Inoue, K., Hasegawa, N., Iemitsu, K., Uchida, M., Iemitsu, M., Decreased muscle-derived musclin by chronic resistance exercise is associated with improved insulin resistance in rats with type 2 diabetes. Physiol. Rep., 9, 2019, e14823.
Sánchez, Y.L., Yepes-Calderón, M., Valbuena, L., Milán, A.F., Trillos-Almanza, M.C., Granados, S., Peña, M., Estrada-Castrillón, M., Aristizábal, J.C., Narvez-Sanchez, R., et al. Musclin is related to insulin resistance and body composition, but not to body mass index or cardiorespiratory capacity in adults. Endocrinol. Metab. (Seoul) 36 (2021), 1055–1068.
Bella, P., Farini, A., Banfi, S., Parolini, D., Tonna, N., Meregalli, M., Belicchi, M., Erratico, S., D'Ursi, P., Bianco, F., et al. Blockade of IGF2R improves muscle regeneration and ameliorates Duchenne muscular dystrophy. EMBO Mol. Med., 12, 2020, e11019.
Zhu, Y., Gui, W., Tan, B., Du, Y., Zhou, J., Wu, F., Li, H., Lin, X., IGF2 deficiency causes mitochondrial defects in skeletal muscle. Clin. Sci. (Lond.) 135 (2021), 979–990.
Soriano-Arroquia, A., McCormick, R., Molloy, A.P., McArdle, A., Goljanek-Whysall, K., Age-related changes in miR-143-3p: Igfbp5 interactions affect muscle regeneration. Aging Cell 15 (2016), 361–369.
Arany, Z., Foo, S.Y., Ma, Y., Ruas, J.L., Bommi-Reddy, A., Girnun, G., Cooper, M., Laznik, D., Chinsomboon, J., Rangwala, S.M., et al. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451 (2008), 1008–1012.
Hoffman, N.J., Parker, B.L., Chaudhuri, R., Fisher-Wellman, K.H., Kleinert, M., Humphrey, S.J., Yang, P., Holliday, M., Trefely, S., Fazakerley, D.J., et al. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. Cell Metab. 22 (2015), 922–935.
Potts, G.K., McNally, R.M., Blanco, R., You, J.S., Hebert, A.S., Westphall, M.S., Coon, J.J., Hornberger, T.A., A map of the phosphoproteomic alterations that occur after a bout of maximal-intensity contractions. J. Physiol. 595 (2017), 5209–5226.
Cho, Y., Tachibana, S., Hazen, B.C., Moresco, J.J., Yates, J.R. 3rd., Kok, B., Saez, E., Ross, R.S., Russell, A.P., Kralli, A., Perm1 regulates CaMKII activation and shapes skeletal muscle responses to endurance exercise training. Mol. Metab. 23 (2019), 88–97.
Schneider, C.A., Rasband, W.S., Eliceiri, K.W., NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9 (2012), 671–675.
Love, M.I., Huber, W., Anders, S., Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15, 2014, 550.
Tyanova, S., Temu, T., Cox, J., The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat. Protoc. 11 (2016), 2301–2319.
