{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T05:07:51Z","timestamp":1680930471074},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute of Basic Medical Sciences, University of Oslo"},{"name":"Throne Holst Foundation"},{"name":"Western Norway Regional Health Authority"},{"name":"Deutsche Forschungsgemeinschaft","award":["209933838\u2014SFB 1052"]},{"name":"Deutsches Zentrum f\u00fcr Diabetesforschung","award":["82DZD00601"]},{"name":"Trond Mohn Stiftelse"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Proteoglycans are central components of the extracellular matrix (ECM) and binding partners for inflammatory chemokines. Morphological differences in the ECM and increased inflammation are prominent features of the white adipose tissues in patients with obesity. The impact of obesity and weight loss on the expression of specific proteoglycans in adipose tissue is not well known. This study aimed to investigate the relationship between adiposity and proteoglycan expression. We analyzed transcriptomic data from two human bariatric surgery cohorts. In addition, RT-qPCR was performed on adipose tissues from female and male mice fed a high-fat diet. Both visceral and subcutaneous adipose tissue depots were analyzed. Adipose mRNA expression of specific proteoglycans, proteoglycan biosynthetic enzymes, proteoglycan partner molecules, and other ECM-related proteins were altered in both human cohorts. We consistently observed more profound alterations in gene expression of ECM targets in the visceral adipose tissues after surgery (among others VCAN (p = 0.000309), OGN (p = 0.000976), GPC4 (p = 0.00525), COL1A1 (p = 0.00221)). Further, gene analyses in mice revealed sex differences in these two tissue compartments in obese mice. We suggest that adipose tissue repair is still in progress long after surgery, which may reflect challenges in remodeling increased adipose tissues. This study can provide the basis for more mechanistic studies on the role of proteoglycans in adipose tissues in obesity.<\/jats:p>","DOI":"10.3390\/ijms24086884","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T08:08:03Z","timestamp":1680854883000},"page":"6884","source":"Crossref","is-referenced-by-count":0,"title":["Obesity Is Associated with Distorted Proteoglycan Expression in Adipose Tissue"],"prefix":"10.3390","volume":"24","author":[{"given":"Astri J.","family":"Meen","sequence":"first","affiliation":[{"name":"Department of Medical Biology, UIT The Arctic University of Norway, 9019 Troms\u00f8, Norway"}]},{"given":"Atanaska I.","family":"Doncheva","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Oslo, 0316 Oslo, Norway"}]},{"given":"Yvonne","family":"B\u00f6ttcher","sequence":"additional","affiliation":[{"name":"EpiGen, Medical Division, Akershus University Hospital, 1474 Nordbyhagen, Norway"},{"name":"Department of Endocrinology, Division of Medicine, Akershus University Hospital, 1478 L\u00f8renskog, Norway"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-6972-1824","authenticated-orcid":false,"given":"Simon N.","family":"Dankel","sequence":"additional","affiliation":[{"name":"Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"},{"name":"Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5020 Bergen, Norway"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-3258-3397","authenticated-orcid":false,"given":"Anne","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-0208-2065","authenticated-orcid":false,"given":"Matthias","family":"Bl\u00fcher","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany"},{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"}]},{"given":"Johan","family":"Fern\u00f8","sequence":"additional","affiliation":[{"name":"Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"},{"name":"Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5020 Bergen, Norway"}]},{"given":"Gunnar","family":"Mellgren","sequence":"additional","affiliation":[{"name":"Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"},{"name":"Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, 5020 Bergen, Norway"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-5160-4571","authenticated-orcid":false,"given":"Adhideb","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"}]},{"given":"Wenfei","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Food, Nutrition and Health, ETH Zurich, 8092 Schwerzenbach, Switzerland"}]},{"given":"Hua","family":"Dong","sequence":"additional","affiliation":[{"name":"Institute of Food, Nutrition and Health, ETH Zurich, 8092 Schwerzenbach, Switzerland"}]},{"ORCID":"http:\/\/orcid.org\/0009-0002-3360-5455","authenticated-orcid":false,"given":"Falko","family":"No\u00e9","sequence":"additional","affiliation":[{"name":"Institute of Food, Nutrition and Health, ETH Zurich, 8092 Schwerzenbach, Switzerland"}]},{"given":"Christian","family":"Wolfrum","sequence":"additional","affiliation":[{"name":"Institute of Food, Nutrition and Health, ETH Zurich, 8092 Schwerzenbach, Switzerland"}]},{"given":"Gunnar","family":"Pejler","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Uppsala University, 75123 Uppsala, Sweden"}]},{"given":"Knut Tomas","family":"Dalen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Oslo, 0316 Oslo, Norway"}]},{"given":"Svein O.","family":"Kolset","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Oslo, 0316 Oslo, Norway"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1203\/01.PDR.0000059753.61905.58","article-title":"Genetics and the Pathophysiology of Obesity","volume":"53","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R14","DOI":"10.1186\/gb-2008-9-1-r14","article-title":"Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity","volume":"9","author":"Henegar","year":"2008","journal-title":"Genome Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1146\/annurev-physiol-060721-092930","article-title":"Adipose Tissue Fibrosis in Obesity: Etiology and Challenges","volume":"84","author":"Marcelin","year":"2022","journal-title":"Annu. Rev. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ruiz-Ojeda, F.J., M\u00e9ndez-Guti\u00e9rrez, A., Aguilera, C.M., and Plaza-D\u00edaz, J. (2019). Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194888"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1172\/JCI45887","article-title":"Adipose tissue remodeling and obesity","volume":"121","author":"Sun","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1172\/JCI88883","article-title":"The ominous triad of adipose tissue dysfunction: Inflammation, fibrosis, and impaired angiogenesis","volume":"127","author":"Crewe","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.cell.2006.02.050","article-title":"A Pericellular Collagenase Directs the 3-Dimensional Development of White Adipose Tissue","volume":"125","author":"Chun","year":"2006","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.3389\/fphar.2019.01661","article-title":"Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules","volume":"10","author":"Walimbe","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_9","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (2015). Essentials of Glycobiology, Cold Spring Harbor Laboratory Press."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1369\/0022155412464638","article-title":"An Introduction to Proteoglycans and Their Localization","volume":"60","author":"Couchman","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1146\/annurev.bi.60.070191.002303","article-title":"Proteoglycans: Structures and interactions","volume":"60","author":"Lindahl","year":"1991","journal-title":"Annu. Rev. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3389\/fimmu.2020.00769","article-title":"Proteoglycans in Obesity-Associated Metabolic Dysfunction and Meta-Inflammation","volume":"11","author":"Pessentheiner","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.4049\/jimmunol.1100806","article-title":"Serglycin: A Structural and Functional Chameleon with Wide Impact on Immune Cells","volume":"187","author":"Kolset","year":"2011","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1210\/jc.2015-4304","article-title":"Increased Basement Membrane Components in Adipose Tissue During Obesity: Links with TGFbeta and Metabolic Phenotypes","volume":"101","author":"Reggio","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4614","DOI":"10.1038\/s41598-018-37501-x","article-title":"Absence of the proteoglycan decorin reduces glucose tolerance in overfed male mice","volume":"9","author":"Sommervoll","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dankel, S., Fadnes, D.J., Stavrum, A.-K., Stansberg, C., Holdhus, R., Van Hoang, T.T., Veum, V.L., Christensen, B.J., V\u00e5ge, V., and Sagen, J.V. (2010). Switch from Stress Response to Homeobox Transcription Factors in Adipose Tissue After Profound Fat Loss. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011033"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4049\/jimmunol.2100231","article-title":"Serglycin Is Involved in Adipose Tissue Inflammation in Obesity","volume":"208","author":"Doncheva","year":"2022","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1111\/febs.14818","article-title":"The extracellular matrix as a multitasking player in disease","volume":"286","author":"Theocharis","year":"2019","journal-title":"FEBS J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.matbio.2022.02.005","article-title":"Matrisome alterations in obesity\u2014Adipose tissue transcriptome study on monozygotic weight-discordant twins","volume":"108","author":"Kaartinen","year":"2022","journal-title":"Matrix Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1038\/s41366-022-01187-z","article-title":"Small fragments of hyaluronan are increased in individuals with obesity and contribute to low-grade inflammation through TLR-mediated activation of innate immune cells","volume":"46","author":"Romo","year":"2022","journal-title":"Int. J. Obes."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.sbi.2017.12.011","article-title":"Specificity of glycosaminoglycan\u2013protein interactions","volume":"50","author":"Lindahl","year":"2018","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"C1271","DOI":"10.1152\/ajpcell.00095.2022","article-title":"The glycosaminoglycan interactome 2.0","volume":"322","author":"Vallet","year":"2022","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E506","DOI":"10.1152\/ajpendo.00586.2009","article-title":"Insulin-sensitive obesity","volume":"299","author":"Fasshauer","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_24","first-page":"E169","article-title":"Fight against fibrosis in adipose tissue remodeling","volume":"321","author":"Li","year":"2021","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1038\/ncomms4485","article-title":"Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction","volume":"5","author":"Sun","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_26","first-page":"E1016","article-title":"Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation","volume":"299","author":"Spencer","year":"2010","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1210\/en.2014-1042","article-title":"COL6A3 Is Regulated by Leptin in Human Adipose Tissue and Reduced in Obesity","volume":"156","author":"McCulloch","year":"2015","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1002\/oby.20758","article-title":"COL6A3 expression in adipocytes associates with insulin resistance and depends on PPARgamma and adipocyte size","volume":"22","author":"Dankel","year":"2014","journal-title":"Obesity"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1002\/oby.21565","article-title":"Reduced expression of collagen VI alpha 3 (COL6A3) confers resistance to inflammation-induced MCP1 expression in adipocytes","volume":"24","author":"Gesta","year":"2016","journal-title":"Obesity"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1136\/gutjnl-2020-323106","article-title":"Effect of green-Mediterranean diet on intrahepatic fat: The DIRECT PLUS randomised controlled trial","volume":"70","author":"Meir","year":"2021","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1210\/jc.2017-00138","article-title":"The FAT Score, a Fibrosis Score of Adipose Tissue: Predicting Weight-Loss Outcome After Gastric Bypass","volume":"102","author":"Lassen","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/ijo.2009.2","article-title":"A proposed clinical staging system for obesity","volume":"33","author":"Sharma","year":"2009","journal-title":"Int. J. Obes."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1159\/000494295","article-title":"Effects of Weight Loss on Glutathione Peroxidase 3 Serum Concentrations and Adipose Tissue Expression in Human Obesity","volume":"11","author":"Langhardt","year":"2018","journal-title":"Obes. Facts"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nprot.2014.006","article-title":"Full-length RNA-seq from single cells using Smart-seq2","volume":"9","author":"Picelli","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, L., Nie, F., Sicotte, H., Li, Y., Eckel-Passow, J.E., Dasari, S., Vedell, P.T., Barman, P., Wang, L., and Weinshiboum, R. (2016). Measure transcript integrity using RNA-seq data. BMC Bioinform., 17.","DOI":"10.1186\/s12859-016-0922-z"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.12688\/f1000research.29032.2","article-title":"Sustainable data analysis with Snakemake","volume":"10","author":"Jablonski","year":"2021","journal-title":"F1000Res"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.21105\/joss.03167","article-title":"Visualizations with statistical details: The \u2018ggstatsplot\u2019 approach","volume":"6","author":"Patil","year":"2021","journal-title":"J. Open Source Softw."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/6884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T08:23:28Z","timestamp":1680855808000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/6884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,7]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24086884"],"URL":"http:\/\/dx.doi.org\/10.3390\/ijms24086884","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":["Inorganic Chemistry","Organic Chemistry","Physical and Theoretical Chemistry","Computer Science Applications","Spectroscopy","Molecular Biology","General Medicine","Catalysis"],"published":{"date-parts":[[2023,4,7]]}}}