{"doi":"10.2337/db22-0035","title":"Deficient Caveolin-1 Synthesis in Adipocytes Stimulates Systemic Insulin-Independent Glucose Uptake via Extracellular Vesicles","abstract":"Caveolin-1 (cav1) is an important structural and signaling component of plasma membrane invaginations called caveolae and is abundant in adipocytes. As previously reported, adipocyte-specific ablation of the cav1 gene (ad-cav1 knockout [KO] mouse) does not result in elimination of the protein, as cav1 protein traffics to adipocytes from neighboring endothelial cells. However, this mouse is a functional KO because adipocyte caveolar structures are depleted. Compared with controls, ad-cav1KO mice on a high-fat diet (HFD) display improved whole-body glucose clearance despite complete loss of glucose-stimulated insulin secretion, blunted insulin-stimulated AKT activation in metabolic tissues, and partial lipodystrophy. The cause is increased insulin-independent glucose uptake by white adipose tissue (AT) and reduced hepatic gluconeogenesis. Furthermore, HFD-fed ad-cav1KO mice display significant AT inflammation, fibrosis, mitochondrial dysfunction, and dysregulated lipid metabolism. The glucose clearance phenotype of the ad-cav1KO mice is at least partially mediated by AT small extracellular vesicles (AT-sEVs). Injection of control mice with AT-sEVs from ad-cav1KO mice phenocopies ad-cav1KO characteristics. Interestingly, AT-sEVs from ad-cav1KO mice propagate the phenotype of the AT to the liver. These data indicate that ad-cav1 is essential for healthy adaptation of the AT to overnutrition and prevents aberrant propagation of negative phenotypes to other organs by EVs.","journal":"Diabetes","year":2022,"id":253647,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":617454,"name":"Shiuhwei Chen","orcid":null,"position":1,"is_corresponding":false},{"id":850313,"name":"Dawei Bu","orcid":null,"position":2,"is_corresponding":false},{"id":572488,"name":"Christy Gliniak","orcid":"0000-0003-3806-6112","position":3,"is_corresponding":false},{"id":282947,"name":"Ingrid Wernstedt Asterholm","orcid":"0000-0002-0755-5784","position":4,"is_corresponding":false},{"id":734655,"name":"Xin Xin Yu","orcid":"0000-0001-8776-393X","position":5,"is_corresponding":false},{"id":616309,"name":"Nolwenn Joffin","orcid":"0000-0003-2574-2089","position":6,"is_corresponding":false},{"id":660547,"name":"Camila Oliveira de Souza","orcid":"0000-0001-6749-9545","position":7,"is_corresponding":false},{"id":616308,"name":"Jan‐Bernd Funcke","orcid":"0000-0002-2596-3167","position":8,"is_corresponding":false},{"id":312748,"name":"Da Young Oh","orcid":null,"position":9,"is_corresponding":false},{"id":341550,"name":"Oleg Varlamov","orcid":"0000-0003-0294-215X","position":10,"is_corresponding":false},{"id":412763,"name":"Jacob J. Robino","orcid":null,"position":11,"is_corresponding":false},{"id":275030,"name":"Ruth Gordillo","orcid":"0000-0001-6533-2493","position":12,"is_corresponding":false},{"id":275031,"name":"Philipp E. Scherer","orcid":"0000-0003-0680-3392","position":13,"is_corresponding":false},{"id":616307,"name":"Clair Crewe","orcid":"0000-0002-3117-5327","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:24:59.596040Z","pmid":"35880782","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}