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Zimmermann, S.* ; Roomp, K.* ; Meyer, H.J.* ; Mathew, A.* ; Struck, M.F.* ; Blüher, M. ; Martin, H.N.G. ; Keller, M. ; Landgraf, K. ; Körner, A. ; Hoffmann, A. ; Böttcher, Y.* ; Biemann, K.* ; Ghosh, A.* ; Wolfrum, C.* ; Noé, F.* ; Isermann, B.* ; Schneider, J.G.* ; Biemann, R.*

Association of lifestyle-induced weight loss with gene expression in subcutaneous adipose tissue in metabolic syndrome.

J. Diabetes 17:e70083 (2025)

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AIMS: Lifestyle-induced weight loss (LIWL) is considered an effective therapy for the treatment of metabolic syndrome (MetS). 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 months of LIWL on transcriptional regulation in subcutaneous adipose tissue (SAT). Aiming to identify a LIWL-associated "gene signature" in SAT, DEGs were fitted into a linear regression model. MATERIALS AND METHODS: The study is embedded in a prospective, two-arm, controlled, monocentric, randomized, 6-month interventional trial in individuals with MetS following LIWL. The trial included 43 nonsmoking, nondiabetic men aged 45-55 years with MetS. RESULTS: In total, we identified 642 DEGs in SAT after 6 months of LIWL. The identified DEGs were validated in two cross-sectional 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: 0.906-1.0) associated with a loss of more than 10% of initial body weight that was maintained for at least 12 months after LIWL, namely SUMO3 (Small ubiquitin-related modifier 3), PRKG2 (Protein Kinase CGMP-Dependent 2), and ADAP2 (ArfGAP with Dual PH Domains 2). CONCLUSION: 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.

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