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As regulators of membrane architecture, energy balance, inflammation, and cellular signalling, lipids offer a powerful framework for understanding metabolic dysfunction. In veterinary medicine, however, lipidomics remains comparatively underdeveloped. In cats, lipid metabolism is central to disorders such as hepatic lipidosis, cystitis, obesity, diabetes mellitus, and chronic inflammatory enteropathies, yet available data remain limited. This systematic review synthesised current evidence on lipidomics and lipid-focused profiling in feline disease and identified lipid alterations with potential clinical relevance. Methods: Following PRISMA 2020 guidelines, PubMed, ScienceDirect, and Scopus were searched for original studies (1994\u20132026) evaluating lipidomics or lipid-focused profiling in cats. Eligible studies assessed lipid species, fatty acids, lipid mediators, or lipoproteins in disease or physiological states. Owing to methodological heterogeneity, findings were synthesised narratively. Results: Seventeen studies met inclusion criteria, covering hepatic, urinary, gastrointestinal, renal, neurological, oncological, metabolic, and pharmacologically modulated conditions. Recurring alterations involved lipoproteins, triglycerides, phospholipids, sphingolipids, fatty acids, and oxylipins. More consistent patterns emerged in hepatic lipidosis, where lipoprotein disturbances may aid diagnosis; in lower urinary tract disease, where PUFA-derived oxylipins differentiated bacterial from idiopathic cystitis; and in obesity, where phospholipid and triglyceride shifts reflected metabolic risk. Fatty acid remodelling in chronic enteropathies aligned with mucosal inflammation, while sphingolipid changes in neurological disease correlated with severity. Heterogeneity in analytical platforms, dietary control, and study design limited comparability. Conclusions: Feline lipidomics reveals biologically meaningful alterations with emerging diagnostic and prognostic value. Although still developing, lipid-focused approaches may enhance disease characterisation and support translational research. Larger, standardised studies and robust reference datasets are needed to validate lipid signatures for clinical implementation.<\/jats:p>","DOI":"10.3390\/metabo16050330","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:19:29Z","timestamp":1778854769000},"page":"330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipidomic Signatures in Feline Disease: A PRISMA-Guided Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Ana Carolina","family":"Fontes","sequence":"first","affiliation":[{"name":"Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-1428","authenticated-orcid":false,"given":"Carolina Santos","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Center (CECAV)-AL4AnimalS, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina","family":"Matos","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-4473","authenticated-orcid":false,"given":"Isabel Ribeiro","family":"Dias","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Center (CECAV)-AL4AnimalS, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-7477","authenticated-orcid":false,"given":"Francisco","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Chemistry Center of Vila Real, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"RISE-Health\u2014Health Research Network, Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5834-5253","authenticated-orcid":false,"given":"Maria Manuel","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Chemistry Center of Vila Real, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"RISE-Health\u2014Health Research Network, Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5357-3601","authenticated-orcid":false,"given":"Maria Rosario","family":"Domingues","sequence":"additional","affiliation":[{"name":"CESAM, Departament of Chemistry, University of Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"},{"name":"Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8796-5037","authenticated-orcid":false,"given":"Carlos Antunes","family":"Viegas","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, School of Agricultural and Veterinary Sciences (ECAV), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Center (CECAV)-AL4AnimalS, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"CIVG\u2014Vasco da Gama Research Center, University School Vasco da Gama (EUVG), Campus Universit\u00e1rio, Avenida Jos\u00e9 Rodrigues Sousa Fernandes, 3020-210 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.bbalip.2011.06.009","article-title":"Lipid classification, structures and tools","volume":"1811","author":"Fahy","year":"2011","journal-title":"Biochim. 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