{"doi":"10.1002/oby.24064","title":"The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose","abstract":"OBJECTIVE: The objective of this study was to identify the transcriptional landscape of insulin resistance (IR) in subcutaneous adipose tissue (SAT) in humans across the spectrum of obesity. METHODS: We used SAT RNA sequencing in 220 individuals with metabolic phenotyping. RESULTS: We identified a 35-gene signature with high predictive accuracy for homeostatic model of IR that was expressed across a variety of non-immune cell populations. We observed primarily \"protective\" IR associations for adipocyte transcripts and \"deleterious\" associations for macrophage transcripts, as well as a high concordance between SAT and visceral adipose tissue (VAT). Multiple SAT genes exhibited dynamic expression 5 years after weight loss surgery and with insulin stimulation. Using available expression quantitative trait loci in SAT and/or VAT, we demonstrated similar genetic effect sizes of SAT and VAT on type 2 diabetes and BMI. CONCLUSIONS: SAT is conventionally viewed as a metabolic buffer for lipid deposition during positive energy balance, whereas VAT is viewed as a dominant contributor to and prime mediator of IR and cardiometabolic disease risk. Our results implicate a dynamic transcriptional architecture of IR that resides in both immune and non-immune populations in SAT and is shared with VAT, nuancing the current VAT-centric concept of IR in humans.","journal":"Obesity","year":2024,"id":434176,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9375,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":86835,"name":"Quanhu Sheng","orcid":"0000-0001-8951-9295","position":1,"is_corresponding":false},{"id":583218,"name":"Samuel Bailin","orcid":"0000-0003-4990-1013","position":2,"is_corresponding":false},{"id":1240327,"name":"Lucas Massier","orcid":"0000-0002-6199-2643","position":3,"is_corresponding":false},{"id":1240328,"name":"Jiawei Zhong","orcid":"0000-0002-2802-0770","position":4,"is_corresponding":false},{"id":405425,"name":"Mingjian Shi","orcid":"0000-0003-1569-9822","position":5,"is_corresponding":false},{"id":401488,"name":"Celestine N. 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Brown","orcid":"0000-0001-7109-3142","position":15,"is_corresponding":false},{"id":251878,"name":"Saumya Das","orcid":"0000-0002-4521-4606","position":16,"is_corresponding":false},{"id":379419,"name":"Ingrid Dahlman","orcid":"0000-0003-3819-5977","position":17,"is_corresponding":false},{"id":405424,"name":"Jonathan D. Mosley","orcid":"0000-0001-6421-2887","position":18,"is_corresponding":false},{"id":240259,"name":"John R. Koethe","orcid":"0000-0001-6490-6942","position":19,"is_corresponding":false},{"id":630123,"name":"Mikael Rydén","orcid":"0000-0003-4785-1876","position":20,"is_corresponding":false},{"id":427710,"name":"Katherine N. Bachmann","orcid":"0000-0002-6682-4630","position":21,"is_corresponding":false},{"id":251876,"name":"Ravi V. 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