{"doi":"10.1084/jem.20201416","title":"Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance","abstract":"White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance and type 2 diabetes mellitus (T2DM). However, the mechanisms underlying these alterations remain unknown. By analyzing the transcriptome landscape in human adipocytes based on available RNA-seq datasets from lean, obese, and T2DM patients, we reveal elevated mitochondrial reactive oxygen species (ROS) pathway and NF-κB signaling with altered fatty acid metabolism in T2DM adipocytes. Mice with adipose-specific deletion of mitochondrial redox Trx2 develop hyperglycemia, hepatic insulin resistance, and hepatic steatosis. Trx2-deficient WAT exhibited excessive mitophagy, increased inflammation, and lipolysis. Mechanistically, mitophagy was induced through increasing ROS generation and NF-κB-dependent accumulation of autophagy receptor p62/SQSTM1, which recruits damaged mitochondria with polyubiquitin chains. Importantly, administration of ROS scavenger or NF-κB inhibitor ameliorates glucose and lipid metabolic disorders and T2DM progression in mice. Taken together, this study reveals a previously unrecognized mechanism linking mitophagy-mediated adipose inflammation to T2DM with hepatic insulin resistance.","journal":"The Journal of Experimental Medicine","year":2020,"id":51747,"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":149,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"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":259340,"name":"Yanrui Huang","orcid":"0000-0001-5147-1302","position":1,"is_corresponding":false},{"id":259341,"name":"Zhi Song","orcid":"0000-0003-3742-0570","position":2,"is_corresponding":false},{"id":259342,"name":"Huanjiao Jenny Zhou","orcid":"0000-0003-3071-9473","position":3,"is_corresponding":false},{"id":259343,"name":"Haifeng Zhang","orcid":"0000-0001-9141-7458","position":4,"is_corresponding":false},{"id":232238,"name":"Rachel J. Perry","orcid":"0000-0003-0748-8064","position":5,"is_corresponding":false},{"id":232241,"name":"Gerald I. Shulman","orcid":"0000-0003-1529-5668","position":6,"is_corresponding":false},{"id":259344,"name":"Min Wang","orcid":"0000-0002-2479-6096","position":7,"is_corresponding":false},{"id":259339,"name":"Feng He","orcid":"0000-0003-3207-1295","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T20:41:30.009880Z","pmid":"33315085","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":[]}