biostudies-literatureYang ZHIntramural NIH HHSNational Eye InstituteOffice of Dietary SupplementsNEI NIH HHSResearch to Prevent BlindnessFoundation Fighting BlindnessUniversity of UtahFoundation for the National Institutes of HealthNational Heart, Lung, and Blood InstituteNational Institutes of HealthNational Heart Lung and Blood Institute Division of Intramural Research108411https://www.ebi.ac.uk/biostudies/studies/S-EPMC10692724biostudies-literatureUnknown26(12)Very-long-chain polyunsaturated fatty acids (VLCPUFAs; C24-38) constitute a unique class of PUFA that have important biological roles, but the lack of a suitable dietary source has limited research in this field. We produced an n-3 C24-28-rich VLCPUFA-oil concentrated from fish oil to study its bioavailability and physiological functions in C57BL/6J mice. The serum and retinal C24:5 levels increased significantly compared to control after a single-dose gavage, and VLCPUFAs were incorporated into the liver, brain, and eyes after 8-week supplementation. Dietary VLCPUFAs resulted in favorable cardiometabolic changes, and improved electroretinography responses and visual performance. VLCPUFA supplementation changed the expression of genes involved in PPAR signaling pathways. Further <i>in vitro</i> studies demonstrated that the VLCPUFA-oil and chemically synthesized C24:5 are potent agonists for PPARs. The multiple potential beneficial effects of fish oil-derived VLCPUFAs on cardiometabolic risk and eye health in mice support future efforts to develop VLCPUFA-oil into a supplemental therapy.iScienceDietary fish oil enriched in very-long-chain polyunsaturated fatty acid reduces cardiometabolic risk factors and improves retinal function.PMC10692724ZIAEY000450R01 EY034497ZIA EY000546EY14800P30 EY014800EY34497ZIAEY00546ZIA EY000450Yamazaki IArunkumar RSwenson REYang ZHRojulpote KVKun JFDecot HBernstein PSSwaroop ARemaley ATGorusupudi ATang JSato SMondal AKKoch HLydic TAYu ZXYamaguchi HLin ABBrock DCShi ZDPryor MfalseDietary fish oil enriched in very-long-chain polyunsaturated fatty acid reduces cardiometabolic risk factors and improves retinal function.Very-long-chain polyunsaturated fatty acids (VLCPUFAs; C24-38) constitute a unique class of PUFA that have important biological roles, but the lack of a suitable dietary source has limited research in this field. We produced an n-3 C24-28-rich VLCPUFA-oil concentrated from fish oil to study its bioavailability and physiological functions in C57BL/6J mice. The serum and retinal C24:5 levels increased significantly compared to control after a single-dose gavage, and VLCPUFAs were incorporated into the liver, brain, and eyes after 8-week supplementation. Dietary VLCPUFAs resulted in favorable cardiometabolic changes, and improved electroretinography responses and visual performance. VLCPUFA supplementation changed the expression of genes involved in PPAR signaling pathways. Further <i>in vitro</i> studies demonstrated that the VLCPUFA-oil and chemically synthesized C24:5 are potent agonists for PPARs. The multiple potential beneficial effects of fish oil-derived VLCPUFAs on cardiometabolic risk and eye health in mice support future efforts to develop VLCPUFA-oil into a supplemental therapy.2023-01-01T00:00:00Z2023 Dec2026-05-28T08:57:15.613Z2025-05-18T10:37:54.649ZS-EPMC106927243804706910.1016/j.isci.2023.108411