{"doi":"10.1002/lipd.12351","title":"Structurally‐engineered fatty acid 1024 (<scp>SEFA</scp>‐1024) improves diet‐induced obesity, insulin resistance, and fatty liver disease","abstract":"Obesity is a global epidemic that drives morbidity and mortality through cardiovascular disease, diabetes, and non-alcoholic fatty liver disease (NAFLD). No definitive therapy has been approved to improve glycemic control and treat NAFLD in obese patients. Here, we investigated a semi-synthetic, long chain, structurally-engineered fatty acid-1024 (SEFA-1024), as a treatment for obesity-induced hyperglycemia, insulin-resistance, and fatty liver disease in rodent models. A single dose of SEFA-1024 was administered to evaluate glucose tolerance and active glucagon-like peptide 1 (GLP-1) in lean rats in the presence and absence of a DPP-4 inhibitor. The effects of SEFA-1024 on weight loss and glycemic control were assessed in genetic (ob/ob) and environmental (high-fat diet) murine models of obesity. Liver histology, serum liver enzymes, liver lipidomics, and hepatic gene expression were also assessed in the high-fat diet murine model. SEFA-1024 reversed obesity-associated insulin resistance and improved glycemic control. SEFA-1024 increased active GLP-1. In a long-term model of diet-induced obesity, SEFA-1024 reversed excessive weight gain, hepatic steatosis, elevated liver enzymes, hepatic lipotoxicity, and promoted fatty acid metabolism. SEFA-1024 is an enterohepatic-targeted, eicosapentaenoic acid derivative that reverses obesity-induced dysregulated glucose metabolism and hepatic lipotoxicity in genetic and dietary rodent models of obesity. The mechanism by which SEFA-1024 works may include increasing aGLP-1, promoting fatty acid oxidation, and inhibiting hepatic triglyceride formation. SEFA-1024 may serve as a potential treatment for obesity-related diabetes and NAFLD.","journal":"Lipids","year":2022,"id":292357,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9403,"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":510504,"name":"Bennet S. Cho","orcid":"0000-0002-1440-0019","position":1,"is_corresponding":false},{"id":510500,"name":"Lumeng J. Yu","orcid":"0000-0003-0370-4444","position":2,"is_corresponding":false},{"id":444935,"name":"Amy Pan","orcid":"0000-0002-7199-7704","position":3,"is_corresponding":false},{"id":511145,"name":"Victoria H. Ko","orcid":null,"position":4,"is_corresponding":false},{"id":510501,"name":"Duy T. Dao","orcid":"0000-0001-9915-7080","position":5,"is_corresponding":false},{"id":238137,"name":"Michael Feigh","orcid":"0000-0001-5274-8799","position":6,"is_corresponding":false},{"id":510503,"name":"Lorenzo Anez‐Bustillos","orcid":"0000-0001-6149-4444","position":7,"is_corresponding":false},{"id":531933,"name":"Gillian L. Fell","orcid":"0000-0001-9595-2730","position":8,"is_corresponding":false},{"id":976939,"name":"David A. Fraser","orcid":null,"position":9,"is_corresponding":false},{"id":354285,"name":"Kathleen M. Gura","orcid":"0000-0002-0431-896X","position":10,"is_corresponding":false},{"id":354288,"name":"Mark Puder","orcid":"0000-0002-7941-2926","position":11,"is_corresponding":false},{"id":976938,"name":"Jordon D. Secor","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T00:30:46.209549Z","pmid":"35778847","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":[]}