Transcriptome of Subcutaneous Adipose Tissue reflect Membrane Dysfunction and Impaired Oxidative Processes in T2D across Heterogenous Populations

Transcriptome of Subcutaneous Adipose Tissue reflect Membrane Dysfunction and Impaired Oxidative Processes in T2D across Heterogenous Populations | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Transcriptome of Subcutaneous Adipose Tissue reflect Membrane Dysfunction and Impaired Oxidative Processes in T2D across Heterogenous Populations Ellen Faergestad Mosleth, Kristian Hovde Liland, Fransisco Martin Barajas-Olmos, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7053974/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Unravelling the aetiology of type 2 diabetes (T2D) is challenged by heterogeneity caused by differences in obesity, the ratio of visceral to subcutaneous adipose tissue (VAT/SAT), genetic origin, and ethnicity. We hypothesized that the SAT transcriptome across independent adipose-matched cohorts may reveal novel insight. The SAT transcriptome from three adipose-matched human cohorts, all with and without T2D, were analysed and combined into new cross-cohort datasets using a novel approach for data integration (General Effect Modelling, GEM) to identify common transcriptome patterns of T2D across the cohorts. Two cohorts had the phenotype high body mass index (BMI) subjected to bariatric surgery, and one had the phenotype high VAT/SAT ratio without high BMI. The multivariate SAT transcriptome patterns associated with T2D across all cohorts included dysfunctional membranes and down-regulation of fatty acid β-oxidation, white adipose tissue differentiation, and protein folding. An extensive inflammatory pattern was observed under high BMI, independently of T2D, whereas a small set of inflammatory markers reflecting gut microbiota was elevated specifically in T2D. Our interpretation is that the fundamental aetiology of T2D in SAT is failure in oxidative membrane potential, leading to impairment of physiologically important adipose processes. Health sciences/Biomarkers Biological sciences/Computational biology and bioinformatics Health sciences/Diseases Health sciences/Endocrinology Biological sciences/Genetics Type 2 diabetes obesity membrane dysfunction impaired oxidative potential gut microbiome multivariate analysis general effect modelling Full Text Additional Declarations No competing interests reported. Supplementary Files Legendsofsuppltables.docx 2025.07.05MoslethT2DSupplementarytablesandfiguresSciRep.docx TableS1a.Cohorts1and2.Downregulatedgenes.xlsx TableS1b.Cohorts1and2.Upregulatedgenes.xlsx TableS2a.Cohort3.Downregulatedgenes.xlsx TableS2b.Cohort3.Upregulatedgenes.xlsx TableS3a.Cohorts123.Commondownregulatedgenes.xlsx TableS3b.Cohorts123.Commonupregulatedgenes.xlsx TableS4a.SAT.Cohort1ANOVABariatricSurgery.Downregulatedafterthesurgery.xlsx TableS4b.SAT.Cohort1ANOVABariatricSurgery.Upregulatedafterthesurgery.xlsx TableS5a.Cohort1.GenesnegasstoT2DinGEMPLSofcohort1and2andupregulatedbyBSincohort1byANOVA.xlsx TableS5b.Cohort1.GenesposasstoT2DinGEMPLSofcohort1and2anddownregulatedbyBSincohort1byANOVA.xlsx TableS6a.Cohort1.Design.Clinics.txt TableS6b.Cohort1.Features.t.txt TableS6c.Cohort2.Design.Clinics.txt TableS6d.Cohort2.Features.t.txt TableS6e.Cohort3.Design.txt TableS6f.Cohort3.Features.t.txt Fig.S13.LoadingdataandrunninganalysesinR.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 16 Nov, 2025 Reviewers agreed at journal 07 Nov, 2025 Reviewers invited by journal 05 Nov, 2025 Editor assigned by journal 04 Nov, 2025 Editor invited by journal 18 Jul, 2025 Submission checks completed at journal 16 Jul, 2025 First submitted to journal 16 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7053974","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":542657647,"identity":"02db1433-8897-4b28-a10e-eca20e795473","order_by":0,"name":"Ellen Faergestad 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