{"doi":"10.1002/edm2.70031","title":"The Role of Serum Free Fatty Acids in Endothelium‐Dependent Microvascular Function","abstract":"BACKGROUND: Elevated serum free fatty acid (FFA) concentration is associated with insulin resistance and is a hallmark of metabolic syndrome. A pathological feature of insulin resistance is impaired endothelial function. OBJECTIVE: To investigate the effect of FFA reduction with either acipimox, a nicotinic acid derivative that impairs lipolysis, or salsalate, a salicylate that reduces basal and inflammation-induced lipolysis, on insulin-mediated endothelium-dependent vasodilation. METHODS: This was a post hoc, combined analysis of two randomised, double-blind, placebo-controlled crossover trials. Sixteen subjects were recruited (6 with metabolic syndrome and 10 controls) and randomised to acipimox 250 mg orally every 6 h for 7 days or placebo. Nineteen subjects were recruited (13 with metabolic syndrome and 6 controls) and randomised to receive salsalate 4.5 g/day for 4 weeks or placebo. The primary outcome was the association between FFA concentration and insulin-mediated vasodilation, measured by venous-occlusion strain-gauge plethysmography at baseline and following FFA modulation with the study drugs. RESULTS: At baseline, FFA concentration (R = -0.35, p = 0.043) and insulin sensitivity (HOMA-IR: R = -0.42, p = 0.016, Adipo-IR: R = -0.39, p = 0.025) predicted insulin-mediated vasodilation. FFA levels were significantly reduced after drug pretreatment (0.604 vs. 0.491 mmol/L, p = 0.036) while insulin levels, insulin sensitivity and inflammatory markers were unchanged. Despite a reduction in circulating FFA with drug therapy, neither insulin-stimulated vasodilation nor insulin sensitivity improved. CONCLUSIONS: Short-term reduction of FFA concentration does not improve insulin-stimulated vasodilation in patients with metabolic syndrome. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00759291 and NCT00760019 (formerly NCT00762827).","journal":"Endocrinology Diabetes & Metabolism","year":2025,"id":531887,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00762827","NCT00760019","NCT00759291"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":971568,"name":"Meaghan CS Courvan","orcid":null,"position":1,"is_corresponding":false},{"id":232624,"name":"Aaron W. Aday","orcid":"0000-0001-6243-3432","position":2,"is_corresponding":false},{"id":501630,"name":"David H. Wasserman","orcid":"0000-0002-3095-2665","position":3,"is_corresponding":false},{"id":264402,"name":"Kevin D. Niswender","orcid":"0000-0001-6994-8738","position":4,"is_corresponding":false},{"id":1413145,"name":"Emily Shardelow","orcid":null,"position":5,"is_corresponding":false},{"id":1413146,"name":"Emily K. Wells","orcid":null,"position":6,"is_corresponding":false},{"id":16591,"name":"Quinn S. Wells","orcid":"0000-0003-3899-0313","position":7,"is_corresponding":false},{"id":381702,"name":"Matthew S. Freiberg","orcid":"0000-0002-3699-4022","position":8,"is_corresponding":false},{"id":51564,"name":"Joshua A. Beckman","orcid":"0000-0001-8332-8439","position":9,"is_corresponding":false},{"id":1031755,"name":"Alexander E. Sullivan","orcid":"0000-0002-1755-0055","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:51:18.928280Z","pmid":"39888728","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":[]}