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In this work, cyanobacterial extracts were screened for lipid reducing activity in zebrafish larvae and in fatty-acid-overloaded human hepatocytes, as well as for glucose uptake in human hepatocytes and ucp1 mRNA induction in murine brown adipocytes. A total of 39 cyanobacteria strains were grown and their biomass fractionated, resulting in 117 chemical fractions. Reduction of neutral lipids in zebrafish larvae was observed for 12 fractions and in the human hepatocyte steatosis cell model for five fractions. The induction of ucp1 expression in murine brown adipocytes was observed in six fractions, resulting in a total of 23 bioactive non-toxic fractions. All extracts were analyzed by untargeted UPLC-Q-TOF-MS mass spectrometry followed by multivariate statistical analysis to prioritize bioactive strains. The metabolite profiling led to the identification of two markers with lipid reducing activity in zebrafish larvae. Putative compound identification using mass spectrometry databases identified them as phosphatidic acid and aromatic polyketides derivatives\u2014two compound classes, which were previously associated with effects on metabolic disorders. In summary, we have identified cyanobacterial strains with promising lipid reducing activity, whose bioactive compounds needs to be identified in the future.<\/jats:p>","DOI":"10.3390\/md21090498","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T02:47:52Z","timestamp":1695091672000},"page":"498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolite Profile Characterization of Cyanobacterial Strains with Bioactivity on Lipid Metabolism Using In Vivo and In Vitro Approaches"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2457-8339","authenticated-orcid":false,"given":"Tiago","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Avenida General Norton de Matos, s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Faculty of Sciences, University of Porto, Rua do Campo Alegre, 1021, 4169-007 Porto, Portugal"}]},{"given":"Krist\u00edn","family":"J\u00f3nsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland"}]},{"given":"Rene","family":"Hernandez-Bautista","sequence":"additional","affiliation":[{"name":"RG Adipocytes & Metabolism, Institute for Diabetes & Obesity, Helmholtz Diabetes Center, Helmholtz Munich, 85764 Neuherberg, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2168-6027","authenticated-orcid":false,"given":"Nat\u00e1lia Gon\u00e7alves","family":"Silva","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Avenida General Norton de Matos, s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Faculty of Sciences, University of Porto, Rua do Campo Alegre, 1021, 4169-007 Porto, Portugal"}]},{"given":"Bego\u00f1a","family":"S\u00e1nchez-Astr\u00e1in","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Avenida General Norton de Matos, s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7702-2273","authenticated-orcid":false,"given":"Afshin","family":"Samadi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland"},{"name":"Joint Laboratory of Applied Ecotoxicology, Korea Institute of Science and Technology Europe (KIST EU), Campus E7.1, 66123 Saarbrucken, Germany"}]},{"given":"Finnur F.","family":"Eiriksson","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland"},{"name":"ArcticMass, Sturlugata 8, 102 Reykjavik, Iceland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0649-8503","authenticated-orcid":false,"given":"Margr\u00e9t","family":"Thorsteinsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland"},{"name":"ArcticMass, Sturlugata 8, 102 Reykjavik, Iceland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-0920","authenticated-orcid":false,"given":"Siegfried","family":"Ussar","sequence":"additional","affiliation":[{"name":"RG Adipocytes & Metabolism, Institute for Diabetes & Obesity, Helmholtz Diabetes Center, Helmholtz Munich, 85764 Neuherberg, Germany"},{"name":"German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7476-9195","authenticated-orcid":false,"given":"Ralph","family":"Urbatzka","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Avenida General Norton de Matos, s\/n, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. 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