{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:30:08Z","timestamp":1788334208988,"version":"build-2803163510"},"reference-count":132,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["201309MOP-311306-BCA-CFBA-40425"],"award-info":[{"award-number":["201309MOP-311306-BCA-CFBA-40425"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein implicated in various functions, including metabolism, tissue regeneration, and functional homeostasis. SPARC\/Sparc declines with ageing but increases with exercise. We aim to verify two hypotheses: (1) SPARC deficiency leads to an ageing-like phenotype (metabolic decline, muscle loss, etc.), and (2) SPARC overexpression would mimic exercise, counteract ageing, and improve age-related changes. Our mice experiments are divided into two parts. First, we explore the consequences of Sparc knockout (KO) and compare them to the ageing effects. We also observe the effects of exercise. In the second part, we study the effects of SPARC overexpression and compare them to the exercise benefits. At the end, we make an analysis of the results to point out the analogies between Sparc KO and the ageing-like phenotype on the one hand and make comparisons between SPARC overexpression and exercise in the context of exercise counteracting ageing. The measurements were mainly related to tissue weights, adiposity, metabolism, and muscle strength. The main findings are that Sparc KO reduced glucose tolerance, muscle glucose transporter expression, and abdominal adipose tissue weight but increased glycogen content in the muscle. SPARC overexpression increased muscle strength, muscle mass, and expressions of the muscle glucose transporter and mitochondrial oxidative phosphorylation but lowered the glycemia and the adiposity, especially in males. Collectively, these findings, and the data we have previously reported, show that Sparc KO mice manifest an ageing-like phenotype, whereas SPARC overexpression and exercise generate similar benefits. The benefits are towards counteracting both the SPARC deficiency-induced ageing-like phenotype as well as reversing the age-related changes. The potential applications of these findings are to build\/optimize Sparc KO-based animal models of various health conditions and, on the other hand, to develop therapies based on introducing SPARC or targeting SPARC-related pathways to mimic exercise against age-related and metabolic disorders.<\/jats:p>","DOI":"10.3390\/metabo12020125","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T05:26:17Z","timestamp":1643433977000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Leads to an Accelerated Ageing Phenotype Which Is Improved by Exercise Whereas SPARC Overexpression Mimics Exercise Effects in Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-1119","authenticated-orcid":false,"given":"Abdelaziz","family":"Ghanemi","sequence":"first","affiliation":[{"name":"Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Laval University, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aicha","family":"Melouane","sequence":"additional","affiliation":[{"name":"Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Laval University, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3519-9024","authenticated-orcid":false,"given":"Mayumi","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2595-6127","authenticated-orcid":false,"given":"Jonny","family":"St-Amand","sequence":"additional","affiliation":[{"name":"Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Laval University, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1161\/CIRCRESAHA.118.312806","article-title":"Age-Related Changes in Glucose Metabolism, Hyperglycemia, and Cardiovascular Risk","volume":"123","author":"Chia","year":"2018","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1249\/00005768-199405000-00009","article-title":"Influence of age on skeletal muscle glucose transport and glycogen metabolism","volume":"26","author":"Cartee","year":"1994","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_3","first-page":"223","article-title":"Aerobic exercise in the elderly: A key to successful aging","volume":"13","author":"Fleg","year":"2012","journal-title":"Discov. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.pmr.2017.06.001","article-title":"Benefits of Exercise in the Older Population","volume":"28","author":"Galloza","year":"2017","journal-title":"Phys. Med. Rehabil. Clin. N. Am."},{"key":"ref_5","first-page":"425","article-title":"Exercise Prescriptions in Older Adults","volume":"95","author":"Lee","year":"2017","journal-title":"Am. Fam. Physician"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Consitt, L.A., Dudley, C., and Saxena, G. (2019). Impact of Endurance and Resistance Training on Skeletal Muscle Glucose Metabolism in Older Adults. Nutrients, 11.","DOI":"10.3390\/nu11112636"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.exger.2010.08.014","article-title":"Regulation of skeletal muscle transcriptome in elderly men after 6 weeks of endurance training at lactate threshold intensity","volume":"45","author":"Riedl","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.lfs.2019.05.070","article-title":"Sparc, an EPS-induced gene, modulates the extracellular matrix and mitochondrial function via ILK\/AMPK pathways in C2C12 cells","volume":"229","author":"Melouane","year":"2019","journal-title":"Life Sci."},{"key":"ref_9","first-page":"e8942","article-title":"Skeletal muscle: Novel and intriguing characteristics as a secretory organ","volume":"7","author":"Aoi","year":"2013","journal-title":"BioDiscovery"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1136\/gutjnl-2011-300776","article-title":"A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise","volume":"62","author":"Aoi","year":"2013","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ghanemi, A., Melouane, A., Yoshioka, M., and St-Amand, J. (2020). Exercise Training of Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Mice Suggests That Exercise-Induced Muscle Phenotype Changes Are SPARC-Dependent. Appl. Sci., 10.","DOI":"10.3390\/app10249108"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ghanemi, A., Yoshioka, M., and St-Amand, J. (2021). Measuring Exercise-Induced Secreted Protein Acidic and Rich in Cysteine Expression as a Molecular Tool to Optimize Personalized Medicine. Genes, 12.","DOI":"10.3390\/genes12111832"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Melouane, A., Carbonell, A., Yoshioka, M., Puymirat, J., and St-Amand, J. (2018). Implication of SPARC in the modulation of the extracellular matrix and mitochondrial function in muscle cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192714"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fphys.2020.00018","article-title":"Plasma Myokine Concentrations After Acute Exercise in Non-obese and Obese Sedentary Women","volume":"11","author":"Garneau","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/acel.12168","article-title":"Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells","volume":"13","author":"Nakamura","year":"2014","journal-title":"Aging Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1210\/en.2002-221044","article-title":"Osteonectin-null mutation compromises osteoblast formation, maturation, and survival","volume":"144","author":"Delany","year":"2003","journal-title":"Endocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S1357-2725(99)00090-4","article-title":"SPARC (osteonectin\/BM-40)","volume":"31","author":"Motamed","year":"1999","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1089\/jop.2015.0057","article-title":"Secreted Protein Acidic and Rich in Cysteine in Ocular Tissue","volume":"31","author":"Scavelli","year":"2015","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1016\/S0021-9258(17)43194-2","article-title":"Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture","volume":"259","author":"Sage","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0945-053X(00)00105-0","article-title":"SPARC, a matricellular protein: At the crossroads of cell-matrix","volume":"19","author":"Brekken","year":"2000","journal-title":"Matrix Biol."},{"key":"ref_21","first-page":"2674","article-title":"SPARC deficiency leads to early-onset cataractogenesis","volume":"39","author":"Norose","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1177\/002215549904701201","article-title":"SPARC, a matricellular glycoprotein with important biological functions","volume":"47","author":"Yan","year":"1999","journal-title":"J. Histochem. Cytochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/stem.3100","article-title":"SPARC promotes self-renewal of limbal epithelial stem cells and ocular surface restoration through JNK and p38-MAPK signaling pathways","volume":"38","author":"Zhu","year":"2020","journal-title":"Stem Cells"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1172\/JCI70921","article-title":"SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome","volume":"124","author":"Alachkar","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1172\/JCI7039","article-title":"Osteopenia and decreased bone formation in osteonectin-deficient mice","volume":"105","author":"Delany","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"36483","DOI":"10.1074\/jbc.M504663200","article-title":"SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity","volume":"280","author":"Barker","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s12079-009-0062-6","article-title":"The role of SPARC in extracellular matrix assembly","volume":"3","author":"Bradshaw","year":"2009","journal-title":"J. Cell Commun. Signal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105627","DOI":"10.1016\/j.biocel.2019.105627","article-title":"Secreted protein acidic and rich in cysteine and bioenergetics: Extracellular matrix, adipocytes remodeling and skeletal muscle metabolism","volume":"117","author":"Ghanemi","year":"2019","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1111\/liv.14857","article-title":"SPARC inhibition accelerates NAFLD-associated hepatocellular carcinoma development by dysregulating hepatic lipid metabolism","volume":"41","author":"Onorato","year":"2021","journal-title":"Liver Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.bbrc.2018.02.129","article-title":"MiR-29 family members interact with SPARC to regulate glucose metabolism","volume":"497","author":"Song","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ghanemi, A., Yoshioka, M., and St-Amand, J. (2020). Secreted Protein Acidic and Rich in Cysteine: Metabolic and Homeostatic Properties beyond the Extracellular Matrix Structure. Appl. Sci., 10.","DOI":"10.3390\/app10072388"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.yjmcc.2009.06.018","article-title":"Cardiac extracellular matrix remodeling: Fibrillar collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC)","volume":"48","author":"McCurdy","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_33","first-page":"1451","article-title":"SPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation","volume":"28","author":"Petersson","year":"2013","journal-title":"Histol. Histopathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1172\/JCI12939","article-title":"SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury","volume":"107","author":"Bradshaw","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41585-021-00476-y","article-title":"Exercise-induced myokines and their effect on prostate cancer","volume":"18","author":"Kim","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ghanemi, A., Yoshioka, M., and St-Amand, J. (2021). Secreted Protein Acidic and Rich in Cysteine as a Molecular Physiological and Pathological Biomarker. Biomolecules, 11.","DOI":"10.3390\/biom11111689"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00223-014-9915-y","article-title":"Skeletal muscle: A brief review of structure and function","volume":"96","author":"Frontera","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Barbalho, S.M., Flato, U.A.P., Tofano, R.J., Goulart, R.A., Guiguer, E.L., Detregiachi, C.R.P., Buchaim, D.V., Ara\u00fajo, A.C., Buchaim, R.L., and Reina, F.T.R. (2020). Physical Exercise and Myokines: Relationships with Sarcopenia and Cardiovascular Complications. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103607"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3389\/fphys.2019.00042","article-title":"Role of Myokines in Regulating Skeletal Muscle Mass and Function","volume":"10","author":"Lee","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"a029785","DOI":"10.1101\/cshperspect.a029785","article-title":"Effects of Exercise and Aging on Skeletal Muscle","volume":"8","author":"Distefano","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1016\/j.jmb.2017.06.019","article-title":"Transcriptional Signatures of Aging","volume":"429","author":"Stegeman","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.mcna.2011.11.003","article-title":"Age as a risk factor","volume":"96","author":"Dhingra","year":"2012","journal-title":"Med. Clin. N. Am."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1076-7460.2003.01751.x","article-title":"Cardiovascular physiology-changes with aging","volume":"12","author":"Cheitlin","year":"2003","journal-title":"Am. J. Geriatr. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mad.2016.10.001","article-title":"Mouse models of ageing and their relevance to disease","volume":"160","author":"Dogan","year":"2016","journal-title":"Mech. Ageing Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.arr.2012.03.010","article-title":"The mouse as a model organism in aging research: Usefulness, pitfalls and possibilities","volume":"12","author":"Vanhooren","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1159\/000454924","article-title":"Energy Metabolism and Ageing in the Mouse: A Mini-Review","volume":"63","author":"Azzu","year":"2017","journal-title":"Gerontology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s10522-019-09837-y","article-title":"D-Galactose-induced accelerated aging model: An overview","volume":"20","author":"Azman","year":"2019","journal-title":"Biogerontology"},{"key":"ref_49","first-page":"177","article-title":"Clinical definition of sarcopenia","volume":"11","author":"Santilli","year":"2014","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ajpath.2016.10.013","article-title":"SPARC Interacts with Actin in Skeletal Muscle in Vitro and in Vivo","volume":"187","author":"Jepsen","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1152\/physrev.00031.2003","article-title":"Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading","volume":"84","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/j.addr.2003.08.002","article-title":"Collagens\u2014Structure, function, and biosynthesis","volume":"55","author":"Gelse","year":"2003","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eabe5738","DOI":"10.1126\/scitranslmed.abe5738","article-title":"Load-induced regulation of tendon homeostasis by SPARC, a genetic predisposition factor for tendon and ligament injuries","volume":"13","author":"Wang","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.2741\/3174","article-title":"The mitochondrial free radical theory of ageing--where do we stand?","volume":"13","author":"Gruber","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2337\/diacare.4.4.493","article-title":"Glucose Intolerance and Aging","volume":"4","author":"DeFronzo","year":"1981","journal-title":"Diabetes Care"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.2337\/db09-0211","article-title":"Regulation of the fibrosis and angiogenesis promoter SPARC\/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose","volume":"58","author":"Kos","year":"2009","journal-title":"Diabetes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1002\/oby.20183","article-title":"Associations among SPARC mRNA expression in adipose tissue, serum SPARC concentration and metabolic parameters in Korean women","volume":"21","author":"Lee","year":"2013","journal-title":"Obesity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"110757","DOI":"10.1016\/j.mce.2020.110757","article-title":"Secreted protein acidic and rich in cysteine (SPARC) regulates thermogenesis in white and brown adipocytes","volume":"506","author":"Mukherjee","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/ajcn\/70.3.405","article-title":"Aging, body composition, and lifestyle: The Fels Longitudinal Study","volume":"70","author":"Guo","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/oby.2011.235","article-title":"Heterogeneity among white adipose tissue depots in male C57BL\/6J mice","volume":"20","author":"Berryman","year":"2012","journal-title":"Obesity"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Jo, J., Gavrilova, O., Pack, S., Jou, W., Mullen, S., Sumner, A.E., Cushman, S.W., and Periwal, V. (2009). Hypertrophy and\/or Hyperplasia: Dynamics of Adipose Tissue Growth. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000324"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3109\/03008207.2010.483747","article-title":"Inactivation of SPARC enhances high-fat diet-induced obesity in mice","volume":"52","author":"Nie","year":"2011","journal-title":"Connect. Tissue Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.arr.2009.08.001","article-title":"Impact of ageing on muscle cell regeneration","volume":"10","author":"Carosio","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/bs.ctdb.2017.08.008","article-title":"Muscle Stem Cells and Aging","volume":"126","author":"Hwang","year":"2018","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ghanemi, A., Yoshioka, M., and St-Amand, J. (2021). Secreted Protein Acidic and Rich in Cysteine as A Regeneration Factor: Beyond the Tissue Repair. Life, 11.","DOI":"10.3390\/life11010038"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1152\/physiolgenomics.00151.2007","article-title":"Osteopenia in Sparc (osteonectin)-deficient mice: Characterization of phenotypic determinants of femoral strength and changes in gene expression","volume":"32","author":"Mansergh","year":"2007","journal-title":"Physiol. Genom."},{"key":"ref_67","first-page":"490","article-title":"Gene expression changes during cataract progression in Sparc null mice: Differential regulation of mouse globins in the lens","volume":"10","author":"Mansergh","year":"2004","journal-title":"Mol. Vis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/sj.gene.6364388","article-title":"Splenic and immune alterations of the Sparc-null mouse accompany a lack of immune response","volume":"8","author":"Rempel","year":"2007","journal-title":"Genes Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"024501","DOI":"10.1115\/1.4047995","article-title":"Mechanical Consequence of Induced Intervertebral Disc Degeneration in the SPARC-Null Mouse","volume":"143","author":"Whittal","year":"2021","journal-title":"J. Biomech. Eng."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1369\/jhc.5A6687.2005","article-title":"Targeted deletion of the SPARC gene accelerates disc degeneration in the aging mouse","volume":"53","author":"Gruber","year":"2005","journal-title":"J. Histochem. Cytochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1042\/CS20180714","article-title":"SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice","volume":"133","author":"Atorrasagasti","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Harries, L.W., McCulloch, L.J., Holley, J.E., Rawling, T.J., Welters, H.J., and Kos, K. (2013). A role for SPARC in the moderation of human insulin secretion. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068253"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"17581","DOI":"10.1038\/s41598-020-74593-w","article-title":"SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic \u03b2 cells","volume":"10","author":"Hu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nature05482","article-title":"Mechanisms linking obesity to insulin resistance and type 2 diabetes","volume":"444","author":"Kahn","year":"2006","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"E1323","DOI":"10.1152\/ajpendo.90617.2008","article-title":"Evaluating the glucose tolerance test in mice","volume":"295","author":"Andrikopoulos","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/17461391.2016.1266392","article-title":"No effect of acute and chronic supramaximal exercise on circulating levels of the myokine SPARC","volume":"17","author":"Songsorn","year":"2017","journal-title":"Eur. J. Sport Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/s41574-018-0062-9","article-title":"Sarcopenic obesity in older adults: Aetiology, epidemiology and treatment strategies","volume":"14","author":"Batsis","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ghanemi, A., Yoshioka, M., and St-Amand, J. (2021). Obese Animals as Models for Numerous Diseases: Advantages and Applications. Medicina, 57.","DOI":"10.3390\/medicina57050399"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Ghanemi, A., Yoshioka, M., and St-Amand, J. (2021). Ageing and Obesity Shared Patterns: From Molecular Pathogenesis to Epigenetics. Diseases, 9.","DOI":"10.3390\/diseases9040087"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"154996","DOI":"10.1016\/j.cyto.2020.154996","article-title":"Secreted protein acidic and rich in cysteine and cancer: A homeostatic hormone?","volume":"127","author":"Ghanemi","year":"2020","journal-title":"Cytokine"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10551","DOI":"10.1096\/fj.201900453R","article-title":"Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation","volume":"33","author":"Aoi","year":"2019","journal-title":"FASEB J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1152\/physrev.00038.2012","article-title":"Exercise, GLUT4, and skeletal muscle glucose uptake","volume":"93","author":"Richter","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/10408399009527522","article-title":"Muscle growth and exercise","volume":"29","author":"Pearson","year":"1990","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/MCO.0000000000000335","article-title":"The effects of exercise on muscle strength, body composition, physical functioning and the inflammatory profile of older adults: A systematic review","volume":"20","author":"Liberman","year":"2017","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1152\/japplphysiol.01370.2011","article-title":"Effects of aerobic and\/or resistance training on body mass and fat mass in overweight or obese adults","volume":"113","author":"Willis","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00424-018-2217-x","article-title":"Exercise and the control of muscle mass in human","volume":"471","author":"Francaux","year":"2019","journal-title":"Pflug. Arch.-Eur. J. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1152\/physiol.00038.2018","article-title":"High-Intensity Exercise and Mitochondrial Biogenesis: Current Controversies and Future Research Directions","volume":"34","author":"Bishop","year":"2019","journal-title":"Physiology"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Kwon, J.H., Moon, K.M., and Min, K.W. (2020). Exercise-Induced Myokines can Explain the Importance of Physical Activity in the Elderly: An Overview. Healthcare, 8.","DOI":"10.3390\/healthcare8040378"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s12272-017-0994-y","article-title":"The role of exercise-induced myokines in regulating metabolism","volume":"41","author":"Huh","year":"2018","journal-title":"Arch. Pharmacal Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cmet.2016.01.011","article-title":"Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution","volume":"23","author":"Pedersen","year":"2016","journal-title":"Cell Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"155179","DOI":"10.1016\/j.cyto.2020.155179","article-title":"Secreted protein acidic and rich in cysteine and inflammation: Another homeostatic property?","volume":"133","author":"Ghanemi","year":"2020","journal-title":"Cytokine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1258\/002367776780956917","article-title":"Lifespan, age changes and tumour incidence in an ageing C57BL mouse colony","volume":"10","author":"Rowlatt","year":"1976","journal-title":"Lab. Anim."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/geronj\/30.2.157","article-title":"Gerontological data of C57BL\/6J mice. I. Sex differences in survival curves","volume":"30","author":"Kunstyr","year":"1975","journal-title":"J. Gerontol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1152\/japplphysiol.00991.2004","article-title":"Inter- and intrastrain variation in mouse critical running speed","volume":"98","author":"Billat","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0531-5565(95)02032-2","article-title":"Oxygen consumption in adult and AGED C57BL\/6J mice during acute treadmill exercise of different intensity","volume":"31","author":"Schefer","year":"1996","journal-title":"Exp. Gerontol."},{"key":"ref_96","unstructured":"(2020, December 13). Teklad Global 18% Protein Rodent Diet (Sterilizable). Available online: https:\/\/insights.envigo.com\/hubfs\/resources\/data-sheets\/2018s-datasheet-0915.pdf."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1006\/exer.2000.0884","article-title":"Lenses of SPARC-null mice exhibit an abnormal cell surface-basement membrane interface","volume":"71","author":"Norose","year":"2000","journal-title":"Exp. Eye Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2337\/diabetes.53.2.315","article-title":"Effect of moderate exercise training on peripheral glucose effectiveness, insulin sensitivity, and endogenous glucose production in healthy humans estimated by a two-compartment-labeled minimal model","volume":"53","author":"Nishida","year":"2004","journal-title":"Diabetes"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2114\/ahs1983.11.365","article-title":"The benefits of the low intensity training","volume":"11","author":"Tanaka","year":"1992","journal-title":"Ann. Physiol. Anthr."},{"key":"ref_100","first-page":"818","article-title":"Blood pressure lowering effect of low intensity aerobic training in elderly hypertensive patients","volume":"30","author":"Motoyama","year":"1998","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/S0026-0495(99)90194-4","article-title":"Effects of low-intensity aerobic training on the high-density lipoprotein cholesterol concentration in healthy elderly subjects","volume":"48","author":"Sunami","year":"1999","journal-title":"Metabolism"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1152\/jappl.2000.88.4.1321","article-title":"Aging of skeletal muscle: A 12-yr longitudinal study","volume":"88","author":"Frontera","year":"2000","journal-title":"J. Appl. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/ggi.12209","article-title":"Age-dependent changes in skeletal muscle mass and visceral fat area in Japanese adults from 40 to 79 years-of-age","volume":"14","author":"Yamada","year":"2014","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Miyamoto, T., Shimizu, Y., Matsuo, Y., Otaru, T., Kanzawa, Y., Miyamae, N., Yamada, E., and Katsuno, T. (2021). Effects of exercise intensity and duration on a myokine, secreted protein acidic and rich in cysteine. Eur. J. Sport Sci., 1\u201310.","DOI":"10.1080\/17461391.2021.1953152"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/sj.ijo.0801839","article-title":"A comparison of methods for analyzing glucose and insulin areas under the curve following nine months of exercise in overweight adults","volume":"26","author":"Potteiger","year":"2002","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s12033-013-9672-6","article-title":"A defined methodology for reliable quantification of Western blot data","volume":"55","author":"Taylor","year":"2013","journal-title":"Mol. Biotechnol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"361590","DOI":"10.1155\/2014\/361590","article-title":"The design of a quantitative western blot experiment","volume":"2014","author":"Taylor","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.lfs.2018.11.006","article-title":"Energy and metabolic pathways in trefoil factor family member 2 (Tff2) KO mice beyond the protection from high-fat diet-induced obesity","volume":"215","author":"Ghanemi","year":"2018","journal-title":"Life Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1152\/jappl.1970.28.2.234","article-title":"Determination of glycogen in small tissue samples","volume":"28","author":"Lo","year":"1970","journal-title":"J. Appl. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/B978-0-12-411619-1.00006-9","article-title":"Quantifying size and number of adipocytes in adipose tissue","volume":"537","author":"Parlee","year":"2014","journal-title":"Methods Enzymol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1002\/oby.20165","article-title":"Trefoil factor family member 2 (Tff2) KO mice are protected from high-fat diet-induced obesity","volume":"21","author":"Yoshioka","year":"2013","journal-title":"Obesity"},{"key":"ref_113","unstructured":"(2020, December 15). Available online: https:\/\/www.cyagen.com\/us\/en\/service\/piggybac-transgenic-mouse.html."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2144\/05382RR05","article-title":"Improved real-time RT-PCR method for high-throughput measurements using second derivative calculation and double correction","volume":"38","author":"Paquet","year":"2005","journal-title":"BioTechniques"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Bustin, S.A., Beaulieu, J.F., Huggett, J., Jaggi, R., Kibenge, F.S., Olsvik, P.A., Penning, L.C., and Toegel, S. (2010). MIQE pr\u00e9cis: Practical implementation of minimum standard guidelines for fluorescence-based quantitative real-time PCR experiments. BMC Mol. Biol., 11.","DOI":"10.1186\/1471-2199-11-74"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0165-0270(95)00049-6","article-title":"Quantitative measurement of muscle strength in the mouse","volume":"62","author":"Smith","year":"1995","journal-title":"J. Neurosci. Methods"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"42323","DOI":"10.1038\/srep42323","article-title":"Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice","volume":"7","author":"Takeshita","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0304-4173(83)90003-4","article-title":"Structure of cytochrome c oxidase","volume":"726","author":"Capaldi","year":"1983","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1128\/jb.176.18.5587-5600.1994","article-title":"The superfamily of heme-copper respiratory oxidases","volume":"176","author":"Barquera","year":"1994","journal-title":"J. Bacteriol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/BF00872214","article-title":"Structure and evolution of cytochrome oxidase","volume":"65","author":"Saraste","year":"1994","journal-title":"Antonie Leeuwenhoek"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0304-4173(80)90002-6","article-title":"Cytochrome c oxidase. Towards a clarification of its structure, interactions and mechanism","volume":"594","author":"Azzi","year":"1980","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_123","unstructured":"(2022, January 16). Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/17709."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1002\/elps.200500785","article-title":"Beta-actin is not a reliable loading control in Western blot analysis","volume":"27","author":"Dittmer","year":"2006","journal-title":"Electrophoresis"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1002\/jcp.29975","article-title":"SPARC is a key mediator of TGF-\u03b2-induced renal cancer metastasis","volume":"236","author":"Bao","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"8196","DOI":"10.1074\/jbc.M109.025684","article-title":"SPARC suppresses apoptosis of idiopathic pulmonary fibrosis fibroblasts through constitutive activation of beta-catenin","volume":"285","author":"Chang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.acthis.2013.06.004","article-title":"SPARC is over-expressed in adipose tissues of diet-induced obese rats and causes insulin resistance in 3T3-L1 adipocytes","volume":"116","author":"Shen","year":"2014","journal-title":"Acta Histochem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1530\/EJE-11-0131","article-title":"Elevated plasma levels of SPARC in patients with newly diagnosed type 2 diabetes mellitus","volume":"165","author":"Wu","year":"2011","journal-title":"Eur. J. Endocrinol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S0002-9440(10)61732-4","article-title":"SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells","volume":"159","author":"Yiu","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"40","DOI":"10.18632\/aging.100426","article-title":"Age-related resistance of skeletal muscle-derived progenitor cells to SPARC may explain a shift from myogenesis to adipogenesis","volume":"4","author":"Nakamura","year":"2012","journal-title":"Aging"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1634\/stemcells.2008-0212","article-title":"IFATS collection: Combinatorial peptides identify alpha5beta1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells","volume":"26","author":"Nie","year":"2008","journal-title":"Stem Cells"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4997\/jrcpe.2021.203","article-title":"Exercise: The panacea in management of many ills. Now is the time to engage","volume":"51","author":"Jacunski","year":"2021","journal-title":"J. R. Coll. Physicians Edinb."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/2\/125\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:09:37Z","timestamp":1760134177000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/2\/125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":132,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["metabo12020125"],"URL":"https:\/\/doi.org\/10.3390\/metabo12020125","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]}}}