{"doi":"10.1016/j.celrep.2020.108326","title":"TET2-Loss-of-Function-Driven Clonal Hematopoiesis Exacerbates Experimental Insulin Resistance in Aging and Obesity","abstract":"Human aging is frequently accompanied by the acquisition of somatic mutations in the hematopoietic system that induce clonal hematopoiesis, leading to the development of a mutant clone of hematopoietic progenitors and leukocytes. This somatic-mutation-driven clonal hematopoiesis has been associated with an increased incidence of cardiovascular disease and type 2 diabetes, but whether this epidemiological association reflects a direct, causal contribution of mutant hematopoietic and immune cells to age-related metabolic abnormalities remains unexplored. Here, we show that inactivating mutations in the epigenetic regulator TET2, which lead to clonal hematopoiesis, aggravate age- and obesity-related insulin resistance in mice. This metabolic dysfunction is paralleled by increased expression of the pro-inflammatory cytokine IL-1β in white adipose tissue, and it is suppressed by pharmacological inhibition of NLRP3 inflammasome-mediated IL-1β production. These findings support a causal contribution of somatic TET2 mutations to insulin resistance and type 2 diabetes.","journal":"Cell Reports","year":2020,"id":50202,"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":205,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":245949,"name":"María A. Zuriaga","orcid":"0000-0003-0422-2965","position":1,"is_corresponding":false},{"id":245950,"name":"Virginia Zorita","orcid":"0009-0003-1527-9737","position":2,"is_corresponding":false},{"id":245951,"name":"Susan MacLauchlan","orcid":"0000-0001-9689-0826","position":3,"is_corresponding":false},{"id":245952,"name":"Maya N. Polackal","orcid":"0000-0001-9236-5039","position":4,"is_corresponding":false},{"id":245953,"name":"Vanesa Viana‐Huete","orcid":"0000-0001-8390-1346","position":5,"is_corresponding":false},{"id":245954,"name":"Alba Ferrer-Pérez","orcid":"0000-0002-9378-6115","position":6,"is_corresponding":false},{"id":245955,"name":"Nuria Matesanz","orcid":"0000-0002-5756-3424","position":7,"is_corresponding":false},{"id":248444,"name":"Andrea Herrero-Cervera","orcid":null,"position":8,"is_corresponding":false},{"id":245956,"name":"Soichi Sano","orcid":"0000-0003-2805-6252","position":9,"is_corresponding":false},{"id":245957,"name":"Matthew A. Cooper","orcid":"0000-0003-3147-3460","position":10,"is_corresponding":false},{"id":245958,"name":"Herminia González‐Navarro","orcid":"0000-0001-6883-3808","position":11,"is_corresponding":false},{"id":245959,"name":"Kenneth Walsh","orcid":"0000-0001-7580-2276","position":12,"is_corresponding":false},{"id":245948,"name":"José J. Fuster","orcid":"0000-0002-5970-629X","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-18T20:38:25.860949Z","pmid":"33113366","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":[]}