{"doi":"10.1101/649103","title":"Deep Lipidomics and Molecular Imaging of Unsaturated Lipid Isomers: A Universal Strategy Initiated by mCPBA Epoxidation","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Cellular lipidome is highly regulated through lipogenesis, rendering diverse double-bond positional isomers (C=C isomer) of a given unsaturated lipid species. In recent years, there are increasing reports indicating the physiological roles of C=C isomer compositions associated with diseases, while the biochemistry has not been fully understood due to the challenge in characterizing lipid isomers inherent to conventional mass spectrometry-based lipidomics. To address this challenge, we reported a universal, user-friendly, derivatization-based strategy,\n                  <jats:bold>MELDI</jats:bold>\n                  (\n                  <jats:bold>m</jats:bold>\n                  CPBA\n                  <jats:bold>E</jats:bold>\n                  poxidation for\n                  <jats:bold>L</jats:bold>\n                  ipid\n                  <jats:bold>D</jats:bold>\n                  ouble-bond\n                  <jats:bold>I</jats:bold>\n                  dentification), which enables both large-scale identification and spatial mapping of biological C=C isomers using commercial mass spectrometers without any instrument modification. With the developed liquid-chromatography mass spectrometry (LC-MS) lipidomics workflow, we elucidated more than 100 isomers among mono- and poly-unsaturated fatty acids and glycerophospholipids in both human serum, where novel isomers of low abundance were unambiguously quantified for the first time. The capability of MELDI-LC-MS in lipidome analysis was further demonstrated using the differentiated 3T3-L1 adipocytes, providing an insight into the cellular lipid reprogramming upon stearoyl-coenzyme A desaturase 1 (SCD1) inhibition. Finally, we highlighted the versatility of MELDI coupled with mass spectrometry imaging to spatially resolve cancer-associated alteration of lipid isomers in a metastatic mouse tissue section. Our results suggested that MELDI will contribute to current lipidomics pipelines with a deeper level of structural information, allowing us to investigate underlying lipid biochemistry.\n                </jats:p>","journal":null,"year":null,"id":617509,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1592553,"name":"Hsin-Hsiang Chung","orcid":null,"position":1,"is_corresponding":false},{"id":1592554,"name":"Hsin-Yuan Chang","orcid":null,"position":2,"is_corresponding":false},{"id":1592555,"name":"Chiao-Wei Lin","orcid":null,"position":3,"is_corresponding":false},{"id":1546378,"name":"Ming-Yang Wang","orcid":null,"position":4,"is_corresponding":false},{"id":1592556,"name":"Tang-Long Shen","orcid":null,"position":5,"is_corresponding":false},{"id":261970,"name":"Cheng‐Chih Hsu","orcid":"0000-0002-2892-5326","position":6,"is_corresponding":false},{"id":1592552,"name":"Ting-Hao Kuo","orcid":"0000-0001-5130-0570","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Deep Lipidomics and Molecular Imaging of Unsaturated Lipid Isomers: A Universal Strategy Initiated by mCPBA Epoxidation","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Cellular lipidome is highly regulated through lipogenesis, rendering diverse double-bond positional isomers (C=C isomer) of a given unsaturated lipid species. In recent years, there are increasing reports indicating the physiological roles of C=C isomer compositions associated with diseases, while the biochemistry has not been fully understood due to the challenge in characterizing lipid isomers inherent to conventional mass spectrometry-based lipidomics. To address this challenge, we reported a universal, user-friendly, derivatization-based strategy,\n                  <jats:bold>MELDI</jats:bold>\n                  (\n                  <jats:bold>m</jats:bold>\n                  CPBA\n                  <jats:bold>E</jats:bold>\n                  poxidation for\n                  <jats:bold>L</jats:bold>\n                  ipid\n                  <jats:bold>D</jats:bold>\n                  ouble-bond\n                  <jats:bold>I</jats:bold>\n                  dentification), which enables both large-scale identification and spatial mapping of biological C=C isomers using commercial mass spectrometers without any instrument modification. With the developed liquid-chromatography mass spectrometry (LC-MS) lipidomics workflow, we elucidated more than 100 isomers among mono- and poly-unsaturated fatty acids and glycerophospholipids in both human serum, where novel isomers of low abundance were unambiguously quantified for the first time. The capability of MELDI-LC-MS in lipidome analysis was further demonstrated using the differentiated 3T3-L1 adipocytes, providing an insight into the cellular lipid reprogramming upon stearoyl-coenzyme A desaturase 1 (SCD1) inhibition. Finally, we highlighted the versatility of MELDI coupled with mass spectrometry imaging to spatially resolve cancer-associated alteration of lipid isomers in a metastatic mouse tissue section. Our results suggested that MELDI will contribute to current lipidomics pipelines with a deeper level of structural information, allowing us to investigate underlying lipid biochemistry.\n                </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W3100361502","authors":[],"funders":[{"funder_name":"Fundação para a Ciência e a Tecnologia, I.P.","grant_id":"PTDC/CCI-INF/6762/2020","title":"MS3: New foundations for micro-services and serverless systems"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by-nc","oa_locations":[{"url":"https://figshare.com/articles/Deep_Lipidomics_and_Molecular_Imaging_of_Unsaturated_Lipid_Isomers_A_Universal_Strategy_Initiated_by_mCPBA_Epoxidation/9731261","host_type":"repository"},{"url":"https://figshare.com/articles/Deep_Lipidomics_and_Molecular_Imaging_of_Unsaturated_Lipid_Isomers_A_Universal_Strategy_Initiated_by_mCPBA_Epoxidation/9731261","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/649103","host_type":"publisher"},{"url":"https://doi.org/10.1101/649103","host_type":"repository"},{"url":"https://doi.org/10.1021/acs.analchem.9b02667","host_type":""},{"url":"https://www.biorxiv.org/content/biorxiv/early/2019/06/02/649103.full.pdf","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/31408322","host_type":""},{"url":"https://dx.doi.org/10.1101/649103","host_type":""},{"url":"https://dx.doi.org/10.1021/acs.analchem.9b02667","host_type":""},{"url":"http://dx.doi.org/10.1101/649103","host_type":""}],"fields_of_study":["Mass Spectrometry Techniques and Applications","Metabolomics and Mass Spectrometry Studies","Advanced Proteomics Techniques and Applications","0301 basic medicine","01 natural sciences","0104 chemical sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Lipidomics","Lipidome","Glycerophospholipids","Chemistry","Mass spectrometry","Mass spectrometry imaging","Metabolomics","Lipogenesis","Structural isomer","Biochemistry","Lipid metabolism","Chromatography","Stereochemistry","Phospholipid","Fatty Acids","Molecular Imaging","Mice","Isomerism","3T3-L1 Cells","Animals","Humans","Chromatography, Liquid"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T01:53:19.086287Z","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":[]}