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The role of differentially expressed genes (DEGs) in adipose tissue function and in the success of LIWL in MetS is still unclear. We investigated the effect of 6\u2009months of LIWL on transcriptional regulation in subcutaneous adipose tissue (SAT). Aiming to identify a LIWL\u2010associated \u201cgene signature\u201d in SAT, DEGs were fitted into a linear regression model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The study is embedded in a prospective, two\u2010arm, controlled, monocentric, randomized, 6\u2010month interventional trial in individuals with MetS following LIWL. The trial included 43 nonsmoking, nondiabetic men aged 45\u201355\u2009years with MetS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, we identified 642 DEGs in SAT after 6 months of LIWL. The identified DEGs were validated in two cross\u2010sectional cohorts analyzing SAT from individuals with and without obesity. Gene enrichment analysis of the DEGs revealed the strongest association with cholesterol metabolic processes. Accordingly, DEGs were correlated with the lipid parameters HDL cholesterol, LDL cholesterol, and triglycerides in corresponding serum samples. We identified 3 genes with an AUC of 0.963 (95% CI: 0.906\u20131.0) associated with a loss of more than 10% of initial body weight that was maintained for at least 12\u2009months after LIWL, namely <jats:italic>SUMO3<\/jats:italic> (<jats:italic>Small ubiquitin\u2010related modifier 3<\/jats:italic>), <jats:italic>PRKG2<\/jats:italic> (<jats:italic>Protein Kinase CGMP\u2010Dependent 2<\/jats:italic>), and <jats:italic>ADAP2 (ArfGAP with Dual PH Domains 2<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, we have identified DEGs in SAT after LIWL, which may play an important role in metabolic functions. In particular, altered gene expression in SAT may predict sustained weight loss.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.70083","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T03:07:51Z","timestamp":1744686471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of Lifestyle\u2010Induced Weight Loss With Gene Expression in Subcutaneous Adipose Tissue in Metabolic Syndrome"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9644-8907","authenticated-orcid":false,"given":"Silke","family":"Zimmermann","sequence":"first","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Roomp","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg  Luxembourg Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Jonas","family":"Meyer","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology University of Leipzig Faculty of Medicine  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Mathew","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-3406","authenticated-orcid":false,"given":"Manuel Florian","family":"Struck","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine University Hospital Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bl\u00fcher","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic Obesity and Vascular Research (HI\u2010MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig  Leipzig Germany"},{"name":"Medical Department III\u2014Endocrinology, Nephrology, and Rheumatology Leipzig University Medical Center  Leipzig Germany"},{"name":"German Center for Child and Adolescent Health (DZKJ) Leipzig\/Dresden Partner Site  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4034-4964","authenticated-orcid":false,"given":"Hugo N. 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