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the culture media. However, the exometabolome of cyanobacteria has been poorly studied, and few studies have dwelled on its characterization and bioactivity assessment. In this work, exometabolomes of 56 cyanobacterial strains were characterized by HR-ESI-LC-MS\/MS. Cytotoxicity was assessed on two carcinoma cell lines, HepG2 and HCT116, while the reduction in lipids was tested in zebrafish larvae and in a steatosis model with fatty acid-overloaded human liver cells. The exometabolome analysis using GNPS revealed many complex clusters of unique compounds in several strains, with no identifications in public databases. Three strains reduced viability in HCT116 cells, namely Tolypotrichaceae BACA0428 (30.45%), Aphanizomenonaceae BACA0025 (40.84%), and Microchaetaceae BACA0110 (46.61%). Lipid reduction in zebrafish larvae was only observed by exposure to Dulcicalothrix sp. BACA0344 (60%). The feature-based molecular network shows that this bioactivity was highly correlated with two flavanones, a compound class described in the literature to have lipid reduction activity. The exometabolome characterization of cyanobacteria strains revealed a high chemodiversity, which supports it as a source for novel bioactive compounds, despite most of the time being overlooked.<\/jats:p>","DOI":"10.3390\/md22090412","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T04:35:24Z","timestamp":1725942924000},"page":"412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Screening of Lipid-Reducing Activity and Cytotoxicity of the Exometabolome from Cyanobacteria"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8223-5943","authenticated-orcid":false,"given":"R\u00faben","family":"Luz","sequence":"first","affiliation":[{"name":"Faculdade de Ci\u00eancias e Tecnologia, Universidade dos A\u00e7ores, 9500-321 Ponta Delgada, Portugal"},{"name":"CIBIO, Centro de Investiga\u00e7\u00e3o em Biodiversidade e Recursos Gen\u00e9ticos, InBIO Laborat\u00f3rio Associado, BIOPOLIS Program in Genomics, Biodiversity and Land Planning; UNESCO Chair\u2014Land Within Sea: Biodiversity & Sustainability in Atlantic Islands, Universidade dos A\u00e7ores, 9500-321 Ponta Delgada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8713-6370","authenticated-orcid":false,"given":"Rita","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias e Tecnologia, Universidade dos A\u00e7ores, 9500-321 Ponta Delgada, Portugal"},{"name":"CIBIO, Centro de Investiga\u00e7\u00e3o em Biodiversidade e Recursos Gen\u00e9ticos, InBIO Laborat\u00f3rio Associado, BIOPOLIS Program in Genomics, Biodiversity and Land Planning; UNESCO Chair\u2014Land Within Sea: Biodiversity & Sustainability in Atlantic Islands, Universidade dos A\u00e7ores, 9500-321 Ponta Delgada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5737-296X","authenticated-orcid":false,"given":"V\u00edtor","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias e Tecnologia, Universidade dos A\u00e7ores, 9500-321 Ponta Delgada, Portugal"},{"name":"CIBIO, Centro de Investiga\u00e7\u00e3o em Biodiversidade e Recursos Gen\u00e9ticos, InBIO Laborat\u00f3rio Associado, BIOPOLIS Program in Genomics, Biodiversity and Land Planning; UNESCO Chair\u2014Land Within Sea: Biodiversity & Sustainability in Atlantic Islands, Universidade dos A\u00e7ores, 9500-321 Ponta Delgada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-2417","authenticated-orcid":false,"given":"Vitor","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research\u2014CIIMAR\/CIMAR, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. 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