{"doi":"10.1016/j.isci.2023.106923","title":"A pref-1-controlled non-inflammatory mechanism of insulin resistance","abstract":"While insulin resistance (IR) is associated with inflammation in white adipose tissue, we report a non-inflammatory adipose mechanism of high fat-induced IR mediated by loss of Pref-1. Pref-1, released from adipose Pref-1+ cells with characteristics of M2 macrophages, endothelial cells or progenitors, inhibits MIF release from both Pref-1+ cells and adipocytes by binding with integrin β1 and inhibiting the mobilization of p115. High palmitic acid induces PAR2 expression in Pref-1+ cells, downregulating Pref-1 expression and release in an AMPK-dependent manner. The loss of Pref-1 increases adipose MIF secretion contributing to non-inflammatory IR in obesity. Treatment with Pref-1 blunts the increase in circulating plasma MIF levels and subsequent IR induced by a high palmitic acid diet. Thus, high levels of fatty acids suppress Pref-1 expression and secretion, through increased activation of PAR2, resulting in an increase in MIF secretion and a non-inflammatory adipose mechanism of IR.","journal":"iScience","year":2023,"id":362202,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1071977,"name":"Donghong Cui","orcid":"0000-0001-6941-0997","position":1,"is_corresponding":false},{"id":534631,"name":"Liujun Chen","orcid":null,"position":2,"is_corresponding":false},{"id":1071978,"name":"Haibin Tong","orcid":"0000-0002-7645-3458","position":3,"is_corresponding":false},{"id":1071982,"name":"Hong Wu","orcid":"0000-0002-1912-1609","position":4,"is_corresponding":false},{"id":744457,"name":"Grace K. Muller","orcid":"0000-0002-5433-8571","position":5,"is_corresponding":false},{"id":1072513,"name":"Yadan Qi","orcid":null,"position":6,"is_corresponding":false},{"id":1071980,"name":"Shuxia Wang","orcid":"0000-0001-9750-8668","position":7,"is_corresponding":false},{"id":1115820,"name":"Jinjie Xu","orcid":null,"position":8,"is_corresponding":false},{"id":1115322,"name":"Xiang Gao","orcid":"0000-0002-4674-0317","position":9,"is_corresponding":false},{"id":1115821,"name":"Kathleen E. Fifield","orcid":null,"position":10,"is_corresponding":false},{"id":330403,"name":"Lingyan Wang","orcid":null,"position":11,"is_corresponding":false},{"id":943044,"name":"Zhengyuan Xia","orcid":"0000-0002-7002-5524","position":12,"is_corresponding":false},{"id":1115323,"name":"Jacqueline L. Vanderluit","orcid":"0000-0002-4960-920X","position":13,"is_corresponding":false},{"id":957565,"name":"Suixin Liu","orcid":"0000-0001-7621-0096","position":14,"is_corresponding":false},{"id":255943,"name":"Lin Leng","orcid":"0000-0002-0605-358X","position":15,"is_corresponding":false},{"id":882398,"name":"Guang Sun","orcid":"0000-0003-4300-0134","position":16,"is_corresponding":false},{"id":497820,"name":"John J. McGuire","orcid":"0000-0003-0302-3884","position":17,"is_corresponding":false},{"id":865091,"name":"Lawrence H. Young","orcid":"0000-0003-0295-7298","position":18,"is_corresponding":false},{"id":79005,"name":"Richard Bucala","orcid":"0000-0001-5783-5736","position":19,"is_corresponding":false},{"id":882400,"name":"Dake Qi","orcid":"0000-0003-1353-6093","position":20,"is_corresponding":false},{"id":883019,"name":"Yiheng Huang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T01:14:19.266946Z","pmid":"37283810","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":[]}