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This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up.<\/jats:p>","DOI":"10.3390\/biom15081112","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T09:41:17Z","timestamp":1754300477000},"page":"1112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating Lipid Profiles Indicate Incomplete Metabolic Recovery After Weight Loss, Suggesting the Need for Additional Interventions in Severe Obesity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9483-498X","authenticated-orcid":false,"given":"Alina-Iuliana","family":"Onoiu","sequence":"first","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, Av. Dr. Josep Laporte 2, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9574-6261","authenticated-orcid":false,"given":"Vicente","family":"Cambra-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, Av. Dr. Josep Laporte 2, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4251-585X","authenticated-orcid":false,"given":"Andrea","family":"Jim\u00e9nez-Franco","sequence":"additional","affiliation":[{"name":"Unitat de Recerca Biom\u00e8dica, Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili, Universitat Rovira i Virgili, Av. 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