{"doi":"10.1101/2022.10.13.511807","title":"Endothelial FABP4 constitutes the majority of basal circulating hormone levels and regulates lipolysis-driven insulin secretion","abstract":"Abstract Fatty acid binding protein 4 (FABP4) is a lipid chaperone secreted from adipocytes upon stimulation of lipolysis. Circulating FABP4 levels strongly correlate with body mass index and obesity-related pathologies in experimental models and humans. While adipocytes have been presumed to be the major source of hormonal FABP4, this question has not been addressed definitively in vivo . We generated mice with FABP4 deletion in cells known to express the gene; adipocytes (Adipo-KO), endothelial cells (Endo-KO), myeloid cells (Myeloid-KO), and the whole body (Total-KO) to examine the contribution of these cell types to basal and stimulated plasma FABP4 levels. Unexpectedly, baseline plasma FABP4 was only reduced by ∼25% in Adipo-KO mice, whereas Endo-KO mice showed ∼75% decreases compared to wildtype controls. In contrast, Adipo-KO mice exhibited ∼62% reduction in FABP4 responses to lipolysis, while there was minimal reduction in Endo-KO mice, indicating that adipocytes are the main FABP4 source in lipolysis. We did not detect any myeloid cell contribution to circulating FABP4. Surprisingly, despite the nearly intact FABP4 responses, Endo-KO mice showed blunted lipolysis-induced insulin secretion, identical to Total-KO mice. We conclude that the endothelium is the major source of baseline hormonal FABP4 and is required for the insulin response to lipolysis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":312403,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"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":1010343,"name":"Kacey J. Prentice","orcid":null,"position":1,"is_corresponding":false},{"id":311389,"name":"Alexandra Lee","orcid":"0000-0002-7296-8032","position":2,"is_corresponding":false},{"id":1010344,"name":"Carla Dominguez-Gonzalez","orcid":null,"position":3,"is_corresponding":false},{"id":761297,"name":"Mu Xian Chen","orcid":null,"position":4,"is_corresponding":false},{"id":717777,"name":"Grace Yankun Lee","orcid":"0000-0002-4480-3097","position":5,"is_corresponding":false},{"id":37947,"name":"Gökhan S. Hotamışlıgil","orcid":"0000-0003-2906-1897","position":6,"is_corresponding":false},{"id":565700,"name":"Karen Inouye","orcid":"0000-0003-2743-2121","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:33:36.072096Z","pmid":null,"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":[]}